📚 Article Archive

miR-150 enhances apoptotic and anti-tumor effects of paclitaxel in paclitaxel-resistant ovarian cancer cells by targeting Notch3.

Tae Hoen Kim, Ju-Yeon Jeong, Ju-Yeon Park +5 more · 2017 · Oncotarget · Impact Journals · added 2026-04-24

Tae Hoen Kim, Ju-Yeon Jeong, Ju-Yeon Park, Se-Wha Kim, Jin Hyung Heo, Haeyoun Kang, Gwangil Kim, Hee Jung An Show less

Tumor recurrence by obtaining chemoresistance is a major obstacle to treating ovarian cancer. By TargetScan database and a luciferase reporter assay, we identified miR-150 directly targets

📄 PDF DOI: 10.18632/oncotarget.20348

HEY2

Interaction of iron status with single nucleotide polymorphisms on incidence of type 2 diabetes.

Jihye Kim, Mi Kyung Kim, Sukyoung Jung +4 more · 2017 · PloS one · PLOS · added 2026-04-24

Jihye Kim, Mi Kyung Kim, Sukyoung Jung, Ji Eun Lim, Myung-Hee Shin, Yeon-Jung Kim, Bermseok Oh Show less

The objective of this study is to find single nucleotide polymorphisms (SNPs) associated with a risk of Type 2 diabetes (T2D) in Korean adults and to investigate the longitudinal association between t Show more

The objective of this study is to find single nucleotide polymorphisms (SNPs) associated with a risk of Type 2 diabetes (T2D) in Korean adults and to investigate the longitudinal association between these SNPs and T2D and the interaction effects of iron intake and average hemoglobin level. Data from the KoGES_Ansan and Ansung Study were used. Gene-iron interaction analysis was conducted using a two-step approach. To select candidate SNPs associated with T2D, a total of 7,935 adults at baseline were included in genome-wide association analysis (step one). After excluding T2D prevalent cases, prospective analyses were conducted with 7,024 adults aged 40-69 (step two). The association of selected SNPs and iron status with T2D and their interaction were determined using a Cox proportional hazard model. A total of 3 SNPs [rs9465871 (CDKAL1), rs10761745 (JMJD1C), and rs163177 (KCNQ1)] were selected as candidate SNPs related to T2D. Among them, rs10761745 (JMJD1C) and rs163177 (KCNQ1) were prospectively associated with T2D. High iron intake was also prospectively associated with the risk of T2D after adjusting for covariates. Average hemoglobin level was positively associated with T2D after adjusting for covariates in women. We also found significant interaction effects between rs10761745 (JMJD1C) and average hemoglobin levels on the risk of T2D among women with normal inflammation and without anemia at baseline. In conclusion, KCNQ1 and JMJD1C may prospectively contribute to the risk of T2D incidence among adults over the age of 40 and JMJD1C, but CDKAL1 may not, and iron status may interactively contribute to T2D incidence in women. Show less

📄 PDF DOI: 10.1371/journal.pone.0175681

JMJD1C

The role of MACF1 in nervous system development and maintenance.

Jeffrey J Moffat, Minhan Ka, Eui-Man Jung +2 more · 2017 · Seminars in cell & developmental biology · Elsevier · added 2026-04-24

Jeffrey J Moffat, Minhan Ka, Eui-Man Jung, Amanda L Smith, Woo-Yang Kim Show less

Microtubule-actin crosslinking factor 1 (MACF1), also known as actin crosslinking factor 7 (ACF7), is essential for proper modulation of actin and microtubule cytoskeletal networks. Most MACF1 isoform Show more

Microtubule-actin crosslinking factor 1 (MACF1), also known as actin crosslinking factor 7 (ACF7), is essential for proper modulation of actin and microtubule cytoskeletal networks. Most MACF1 isoforms are expressed broadly in the body, but some are exclusively found in the nervous system. Consequentially, MACF1 is integrally involved in multiple neural processes during development and in adulthood, including neurite outgrowth and neuronal migration. Furthermore, MACF1 participates in several signaling pathways, including the Wnt/β-catenin and GSK-3 signaling pathways, which regulate key cellular processes, such as proliferation and cell migration. Genetic mutation or dysregulation of the MACF1 gene has been associated with neurodevelopmental and neurodegenerative diseases, specifically schizophrenia and Parkinson's disease. MACF1 may also play a part in neuromuscular disorders and have a neuroprotective role in the optic nerve. In this review, the authors seek to synthesize recent findings relating to the roles of MACF1 within the nervous system and explore potential novel functions of MACF1 not yet examined. Show less

📄 PDF DOI: 10.1016/j.semcdb.2017.05.020

MACF1

MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice.

Minhan Ka, Jeffrey J Moffat, Woo-Yang Kim · 2017 · Cerebral cortex (New York, N.Y. : 1991) · Oxford University Press · added 2026-04-24

GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneur Show more

GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain. Show less

no PDF DOI: 10.1093/cercor/bhw319

MACF1

Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target.

Myungjin Jo, Ah Young Chung, Nozomu Yachie +10 more · 2017 · Genome research · Cold Spring Harbor Laboratory · added 2026-04-24

Myungjin Jo, Ah Young Chung, Nozomu Yachie, Minchul Seo, Hyejin Jeon, Youngpyo Nam, Yeojin Seo, Eunmi Kim, Quan Zhong, Marc Vidal, Hae Chul Park, Frederick P Roth, Kyoungho Suk Show less

To understand disease mechanisms, a large-scale analysis of human-yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human-yeas Show more

To understand disease mechanisms, a large-scale analysis of human-yeast genetic interactions was performed. Of 1305 human disease genes assayed, 20 genes exhibited strong toxicity in yeast. Human-yeast genetic interactions were identified by en masse transformation of the human disease genes into a pool of 4653 homozygous diploid yeast deletion mutants with unique barcode sequences, followed by multiplexed barcode sequencing to identify yeast toxicity modifiers. Subsequent network analyses focusing on amyotrophic lateral sclerosis (ALS)-associated genes, such as optineurin ( Show less

📄 PDF DOI: 10.1101/gr.211649.116

MAP2K5

Intestinal, but not hepatic, ChREBP is required for fructose tolerance.

Misung Kim, Inna I Astapova, Sarah N Flier +7 more · 2017 · JCI insight · added 2026-04-24

Misung Kim, Inna I Astapova, Sarah N Flier, Sarah A Hannou, Ludivine Doridot, Ashot Sargsyan, Henry H Kou, Alan J Fowler, Guosheng Liang, Mark A Herman Show less

Increased sugar consumption is a risk factor for the metabolic syndrome including obesity, hypertriglyceridemia, insulin resistance, diabetes, and nonalcoholic fatty liver disease (NAFLD). Carbohydrat Show more

Increased sugar consumption is a risk factor for the metabolic syndrome including obesity, hypertriglyceridemia, insulin resistance, diabetes, and nonalcoholic fatty liver disease (NAFLD). Carbohydrate responsive element-binding protein (ChREBP) is a transcription factor that responds to sugar consumption to regulate adaptive metabolic programs. Hepatic ChREBP is particularly responsive to fructose and global ChREBP-KO mice are intolerant to diets containing fructose. It has recently been suggested that ChREBP protects the liver from hepatotoxicity following high-fructose diets (HFrDs). We directly tested this hypothesis using tissue-specific ChREBP deletion. HFrD increased adiposity and impaired glucose homeostasis in control mice, responses that were prevented in liver-specific ChREBP-KO (LiChKO) mice. Moreover, LiChKO mice tolerated chronic HFrD without marked weight loss or hepatotoxicity. In contrast, intestine-specific ChREBP-KO (IChKO) mice rapidly lost weight after transition to HFrD, and this was associated with dilation of the small intestine and cecum, suggestive of malabsorption. These findings were associated with downregulation of the intestinal fructose transporter, Slc2a5, which is essential for fructose tolerance. Altogether, these results establish an essential role for intestinal, but not hepatic, ChREBP in fructose tolerance. Show less

no PDF DOI: 10.1172/jci.insight.96703

MLXIPL

mTOR controls ChREBP transcriptional activity and pancreatic β cell survival under diabetic stress.

Gia Cac Chau, Dong Uk Im, Tong Mook Kang +5 more · 2017 · The Journal of cell biology · added 2026-04-24

Gia Cac Chau, Dong Uk Im, Tong Mook Kang, Jeong Mo Bae, Won Kim, Suhkneung Pyo, Eun-Yi Moon, Sung Hee Um Show less

Impaired nutrient sensing and dysregulated glucose homeostasis are common in diabetes. However, how nutrient-sensitive signaling components control glucose homeostasis and β cell survival under diabet Show more

Impaired nutrient sensing and dysregulated glucose homeostasis are common in diabetes. However, how nutrient-sensitive signaling components control glucose homeostasis and β cell survival under diabetic stress is not well understood. Here, we show that mice lacking the core nutrient-sensitive signaling component mammalian target of rapamycin (mTOR) in β cells exhibit reduced β cell mass and smaller islets. mTOR deficiency leads to a severe reduction in β cell survival and increased mitochondrial oxidative stress in chemical-induced diabetes. Mechanistically, we find that mTOR associates with the carbohydrate-response element-binding protein (ChREBP)-Max-like protein complex and inhibits its transcriptional activity, leading to decreased expression of thioredoxin-interacting protein (TXNIP), a potent inducer of β cell death and oxidative stress. Consistent with this, the levels of TXNIP and ChREBP were highly elevated in human diabetic islets and Show less

📄 PDF DOI: 10.1083/jcb.201701085

MLXIPL

Nutritional regulation of renal lipogenic factor expression in mice: comparison to regulation in the liver and skeletal muscle.

Suk-Jeong Kim, Ji-Eun Kim, Yong-Woon Kim +2 more · 2017 · American journal of physiology. Renal physiology · added 2026-04-24

Suk-Jeong Kim, Ji-Eun Kim, Yong-Woon Kim, Jong-Yeon Kim, So-Young Park Show less

Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of Show more

Regulation of lipogenesis by pathophysiological factors in the liver and skeletal muscle is well understood; however, regulation in the kidney is still unclear. To elucidate nutritional regulation of lipogenic factors in the kidney, we measured the renal expression of lipogenic transcriptional factors and enzymes during fasting and refeeding in chow-fed and high-fat-fed mice. We also examined the regulatory effect of the liver X receptor (LXR) on the expression of lipogenic factors. The renal gene expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS) was reduced by fasting for 48 h and restored by refeeding, whereas the mRNA levels of forkhead box O (FOXO)1/3 were increased by fasting and restored by refeeding. Accordingly, protein levels of SREBP-1, FAS, and phosphorylated FOXO1/3 were reduced by fasting and restored by refeeding. The patterns of lipogenic factors expression in the kidney were similar to those in the liver and skeletal muscle. However, this phasic regulation of renal lipogenic gene expression was blunted in diet-induced obese mice. LXR agonist TO901317 increased the lipogenic gene expression and the protein levels of SREBP-1 precursor and FAS but not nuclear SREBP-1. Moreover, increases in insulin-induced gene mRNA and nuclear carbohydrate-responsive element binding protein (ChREBP) levels were observed in the TO901317-treated mice. These results suggest that the kidney shows flexible suppression and restoration of lipogenic factors following fasting and refeeding in lean mice, but this is blunted in obese mice. LXR is involved in the renal expression of lipogenic enzymes, and ChREBP may mediate the response. Show less

no PDF DOI: 10.1152/ajprenal.00594.2016

MLXIPL

A critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism.

Ffolliott M Fisher, Misung Kim, Ludivine Doridot +7 more · 2017 · Molecular metabolism · Elsevier · added 2026-04-24

Ffolliott M Fisher, Misung Kim, Ludivine Doridot, Jeremy C Cunniff, Thomas S Parker, Daniel M Levine, Marc K Hellerstein, Lisa C Hudgins, Eleftheria Maratos-Flier, Mark A Herman Show less

Increased fructose consumption is a contributor to the burgeoning epidemic of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates that the metabolic hormone FGF21 is regulated by fruc Show more

Increased fructose consumption is a contributor to the burgeoning epidemic of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates that the metabolic hormone FGF21 is regulated by fructose consumption in humans and rodents and may play a functional role in this nutritional context. Here, we sought to define the mechanism by which fructose ingestion regulates FGF21 and determine whether FGF21 contributes to an adaptive metabolic response to fructose consumption. We tested the role of the transcription factor carbohydrate responsive-element binding protein (ChREBP) in fructose-mediated regulation of FGF21 using ChREBP knockout mice. Using FGF21 knockout mice, we investigated whether FGF21 has a metabolic function in the context of fructose consumption. Additionally, we tested whether a ChREBP-FGF21 interaction is likely conserved in human subjects. Hepatic expression of In summary, ChREBP and FGF21 constitute a signaling axis likely conserved in humans that mediates an essential adaptive response to fructose ingestion that may participate in the pathogenesis of NAFLD and liver fibrosis. Show less

📄 PDF DOI: 10.1016/j.molmet.2016.11.008

MLXIPL

Correction of a pathogenic gene mutation in human embryos.

Hong Ma, Nuria Marti-Gutierrez, Sang-Wook Park +28 more · 2017 · Nature · Nature · added 2026-04-24

Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR Show more

Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR-Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template. By modulating the cell cycle stage at which the DSB was induced, we were able to avoid mosaicism in cleaving embryos and achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations. The efficiency, accuracy and safety of the approach presented suggest that it has potential to be used for the correction of heritable mutations in human embryos by complementing preimplantation genetic diagnosis. However, much remains to be considered before clinical applications, including the reproducibility of the technique with other heterozygous mutations. Show less

no PDF DOI: 10.1038/nature23305

MYBPC3

Identification of pathogenic variants in genes related to channelopathy and cardiomyopathy in Korean sudden cardiac arrest survivors.

Ju Sun Song, Jong-Sun Kang, Young-Eun Kim +7 more · 2017 · Journal of human genetics · Nature · added 2026-04-24

Ju Sun Song, Jong-Sun Kang, Young-Eun Kim, Seung-Jung Park, Kyoung-Min Park, June Huh, June Soo Kim, Hana Cho, Chang-Seok Ki, Young Keun On Show less

Pathogenic variants in genes related to channelopathy and cardiomyopathy are the most common cause of sudden unexplained cardiac death. However, few reports have investigated the frequency and/or spec Show more

Pathogenic variants in genes related to channelopathy and cardiomyopathy are the most common cause of sudden unexplained cardiac death. However, few reports have investigated the frequency and/or spectrum of pathogenic variants in these genes in Korean sudden cardiac arrest survivors. This study aimed to investigate the causative genetic variants of cardiac-associated genes in Korean sudden cardiac arrest survivors. We performed exome sequencing followed by filtering and validation of variants in 100 genes related to channelopathy and cardiomyopathy in 19 Korean patients who survived sudden cardiac arrest. Five of the 19 patients (26.3%) had either a pathogenic variant or a likely pathogenic variant in MYBPC3 (n=1), MYH7 (n=1), RYR2 (n=2), or TNNT2 (n=1). All five variants were missense variants that have been reported previously in patients with channelopathies or cardiomyopathies. Furthermore, an additional 12 patients (63.2%) had more than one variant of uncertain significance. In conclusion, pathogenic or likely pathogenic variants in genes related to channelopathy and cardiomyopathy are not uncommon in Korean sudden cardiac arrest survivors and cardiomyopathy-related genes should be included in the molecular diagnosis of sudden cardiac arrest in Korea. Show less

no PDF DOI: 10.1038/jhg.2017.8

MYBPC3

The transcription factor MafB promotes anti-inflammatory M2 polarization and cholesterol efflux in macrophages.

Hwijin Kim · 2017 · Scientific reports · Nature · added 2026-04-24

Macrophages play pivotal roles in the progression and regression of atherosclerosis. Accumulating evidence suggests that macrophage polarization into an anti-inflammatory M2 state is a key characteris Show more

Macrophages play pivotal roles in the progression and regression of atherosclerosis. Accumulating evidence suggests that macrophage polarization into an anti-inflammatory M2 state is a key characteristic of atherosclerotic plaques undergoing regression. However, the molecular mechanisms underlying this potential association of the M2 polarization with atherosclerosis regression remain poorly understood. Further, human genetic factors that facilitate these anti-atherogenic processes remain largely unknown. We report that the transcription factor MafB plays pivotal roles in promoting macrophage M2 polarization. Further, MafB promotes cholesterol efflux from macrophage foam cells by directly up-regulating its key cellular mediators. Notably, MafB expression is significantly up-regulated in response to various metabolic and immunological stimuli that promote macrophage M2 polarization or cholesterol efflux, and thereby MafB mediates their beneficial effects, in both liver x receptor (LXR)-dependent and independent manners. In contrast, MafB is strongly down-regulated upon elevated pro-inflammatory signaling or by pro-inflammatory and pro-atherogenic microRNAs, miR-155 and miR-33. Using an integrative systems biology approach, we also revealed that M2 polarization and cholesterol efflux do not necessarily represent inter-dependent events, but MafB is broadly involved in both the processes. These findings highlight physiological protective roles that MafB may play against atherosclerosis progression. Show less

no PDF DOI: 10.1038/s41598-017-07381-8

NR1H3

MTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy.

Xi Ma, Shen Zhang, Long He +11 more · 2017 · Autophagy · Taylor & Francis · added 2026-04-24

Xi Ma, Shen Zhang, Long He, Yueguang Rong, Livia Wilz Brier, Qiming Sun, Rong Liu, Weiliang Fan, She Chen, Zhenyu Yue, Joungmok Kim, Kun-Liang Guan, Defa Li, Qing Zhong Show less

NRBF2/Atg38 has been identified as the fifth subunit of the macroautophagic/autophagic class III phosphatidylinositol 3-kinase (PtdIns3K) complex, along with ATG14/Barkor, BECN1/Vps30, PIK3R4/p150/Vps Show more

NRBF2/Atg38 has been identified as the fifth subunit of the macroautophagic/autophagic class III phosphatidylinositol 3-kinase (PtdIns3K) complex, along with ATG14/Barkor, BECN1/Vps30, PIK3R4/p150/Vps15 and PIK3C3/Vps34. However, its functional mechanism and regulation are not fully understood. Here, we report that NRBF2 is a fine tuning regulator of PtdIns3K controlled by phosphorylation. Human NRBF2 is phosphorylated by MTORC1 at S113 and S120. Upon nutrient starvation or MTORC1 inhibition, NRBF2 phosphorylation is diminished. Phosphorylated NRBF2 preferentially interacts with PIK3C3/PIK3R4. Suppression of NRBF2 phosphorylation by MTORC1 inhibition alters its binding preference from PIK3C3/PIK3R4 to ATG14/BECN1, leading to increased autophagic PtdIns3K complex assembly, as well as enhancement of ULK1 protein complex association. Consequently, NRBF2 in its unphosphorylated form promotes PtdIns3K lipid kinase activity and autophagy flux, whereas its phosphorylated form blocks them. This study reveals NRBF2 as a critical molecular switch of PtdIns3K and autophagy activation, and its on/off state is precisely controlled by MTORC1 through phosphorylation. Show less

no PDF DOI: 10.1080/15548627.2016.1269988

PIK3C3

High Glucose Induces Mitochondrial Dysfunction in Retinal Müller Cells: Implications for Diabetic Retinopathy.

Thomas Tien, Joyce Zhang, Tetsuya Muto +3 more · 2017 · Investigative ophthalmology & visual science · added 2026-04-24

Thomas Tien, Joyce Zhang, Tetsuya Muto, Dongjoon Kim, Vijay P Sarthy, Sayon Roy Show less

To investigate whether high glucose (HG) induces mitochondrial dysfunction and promotes apoptosis in retinal Müller cells. Rat retinal Müller cells (rMC-1) grown in normal (N) or HG (30 mM glucose) me Show more

To investigate whether high glucose (HG) induces mitochondrial dysfunction and promotes apoptosis in retinal Müller cells. Rat retinal Müller cells (rMC-1) grown in normal (N) or HG (30 mM glucose) medium for 7 days were subjected to MitoTracker Red staining to identify the mitochondrial network. Digital images of mitochondria were captured in live cells under confocal microscopy and analyzed for mitochondrial morphology changes based on form factor (FF) and aspect ratio (AR) values. Mitochondrial metabolic function was assessed by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a bioenergetic analyzer. Cells undergoing apoptosis were identified by differential dye staining and TUNEL assay, and cytochrome c levels were assessed by Western blot analysis. Cells grown in HG exhibited significantly increased mitochondrial fragmentation compared to those grown in N medium (FF = 1.7 ± 0.1 vs. 2.3 ± 0.1; AR = 2.1 ± 0.1 vs. 2.5 ± 0.2; P < 0.01). OCR and ECAR were significantly reduced in cells grown in HG medium compared to those grown in N medium (steady state: 75% ± 20% of control, P < 0.02; 64% ± 22% of control, P < 0.02, respectively). These cells also exhibited a significant increase (∼2-fold) in the number of apoptotic cells compared to those grown in N medium (P < 0.01), with a concomitant increase in cytochrome c levels (247% ± 94% of control, P < 0.05). Findings indicate that HG-induced mitochondrial morphology changes and subsequent mitochondrial dysfunction may contribute to retinal Müller cell loss associated with diabetic retinopathy. Show less

no PDF DOI: 10.1167/iovs.16-21355

RMC1

Time-course microarray analysis for identifying candidate genes involved in obesity-associated pathological changes in the mouse colon.

Yun Jung Bae, Sung-Eun Kim, Seong Yeon Hong +4 more · 2016 · Genes & nutrition · BioMed Central · added 2026-04-24

Yun Jung Bae, Sung-Eun Kim, Seong Yeon Hong, Taesun Park, Sang Gyu Lee, Myung-Sook Choi, Mi-Kyung Sung Show less

Obesity is known to increase the risk of colorectal cancer. However, mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are not completely understood. The purposes of this stu Show more

Obesity is known to increase the risk of colorectal cancer. However, mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are not completely understood. The purposes of this study were to identify differentially expressed genes in the colon of mice with diet-induced obesity and to select candidate genes as early markers of obesity-associated abnormal cell growth in the colon. C57BL/6N mice were fed normal diet (11% fat energy) or high-fat diet (40% fat energy) and were euthanized at different time points. Genome-wide expression profiles of the colon were determined at 2, 4, 8, and 12 weeks. Cluster analysis was performed using expression data of genes showing log High-fat diet-fed mice showed significant increase in body weight and total visceral fat weight over 12 weeks. Time-course microarray analysis showed that 50, 47, 36, and 411 genes were differentially expressed at 2, 4, 8, and 12 weeks, respectively. Ten cluster profiles representing distinguishable patterns of genes differentially expressed over time were determined. Cluster 4, which consisted of genes showing the most significant alterations in expression in response to high-fat diet over 12 weeks, included Our data indicate that Show less

📄 PDF DOI: 10.1186/s12263-016-0547-x

APOA4

Toll-like Receptor (TLR) Signaling Interacts with CREBH to Modulate High-density Lipoprotein (HDL) in Response to Bacterial Endotoxin.

Aditya Dandekar, Yining Qiu, Hyunbae Kim +10 more · 2016 · The Journal of biological chemistry · American Society for Biochemistry and Molecular Biology · added 2026-04-24

Aditya Dandekar, Yining Qiu, Hyunbae Kim, Jiemei Wang, Xia Hou, Xuebao Zhang, Ze Zheng, Roberto Mendez, Fu-Shin Yu, Ashok Kumar, Deyu Fang, Fei Sun, Kezhong Zhang Show less

Bacterial endotoxin can induce inflammatory and metabolic changes in the host. In this study, we revealed a molecular mechanism by which a stress-inducible, liver-enriched transcription factor, cAMP-r Show more

Bacterial endotoxin can induce inflammatory and metabolic changes in the host. In this study, we revealed a molecular mechanism by which a stress-inducible, liver-enriched transcription factor, cAMP-responsive element-binding protein hepatic-specific (CREBH), modulates lipid profiles to protect the liver from injuries upon the bacterial endotoxin lipopolysaccharide (LPS). LPS challenge can activate CREBH in mouse liver tissues in a toll-like receptor (TLR)/MyD88-dependent manner. Upon LPS challenge, CREBH interacts with TNF receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase that functions as a key mediator of TLR signaling, and this interaction relies on MyD88. Further analysis demonstrated that TRAF6 mediates K63-linked ubiquitination of CREBH to facilitate CREBH cleavage and activation. CREBH directly activates expression of the gene encoding Apolipoprotein A4 (ApoA4) under LPS challenge, leading to modulation of high-density lipoprotein (HDL) in animals. CREBH deficiency led to reduced production of circulating HDL and increased liver damage upon high-dose LPS challenge. Therefore, TLR/MyD88-dependent, TRAF6-facilitated CREBH activation represents a mammalian hepatic defense response to bacterial endotoxin by modulating HDL. Show less

no PDF DOI: 10.1074/jbc.M116.755728

APOA4

Association of Apolipoprotein A5 Gene Polymorphisms with Metabolic Syndrome in the Korean Population.

Young Ree Kim, Seung-Ho Hong · 2016 · Genetic testing and molecular biomarkers · added 2026-04-24

Functional defects of the ApoA5 protein have been identified as risk factors for hypertriglyceridemia, vascular diseases and susceptibility to metabolic syndrome (MetS). These associations are neither Show more

Functional defects of the ApoA5 protein have been identified as risk factors for hypertriglyceridemia, vascular diseases and susceptibility to metabolic syndrome (MetS). These associations are neither strong nor consistent in all populations studied. In this study, we investigated the association between the ApoA5 -1131T>C and -12,238T>C polymorphic loci in Korean patients with MetS. A total of 1074 subjects, including 415 patients with MetS and 659 healthy control subjects, were enrolled to investigate the affect of ApoA5 polymorphisms on risk of MetS. Genotyping of the ApoA5 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism techniques. The CC genotype and the dominant (TT vs. TC+CC) and recessive (TT+TC vs. CC) models of the -1131T>C polymorphism were associated with increased MetS susceptibility (p < 0.001, p = 0.018, and p = 0.002, respectively). The association was male-specific when stratified by gender. With regard to the -12,238T>C polymorphism, the TC and CC genotypes and the dominant (TT vs. TC+CC) and recessive (TT+TC vs. CC) models were frequently found in the patient group, compared with the control group (p = 0.001, p < 0.001, p < 0.001, and p = 0.031, respectively). The T-C, C-T, and C-C haplotypes of the ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with an increased risk for MetS (p < 0.001, p = 0.001, and p < 0.001, respectively). The variant of the ApoA5 -1131T>C polymorphism was also associated with increased triglyceride (TG) levels. Dominant models of ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with the risk components of MetS by the stratification analysis. The -1131C and -12,238C variants and the C-containing haplotypes of ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with higher risk for MetS in the Korean population. The -1131C variant was also associated with the increased level of TG. Show less

no PDF DOI: 10.1089/gtmb.2015.0250

APOA5

Small-molecule binding of the axin RGS domain promotes β-catenin and Ras degradation.

Pu-Hyeon Cha, Yong-Hee Cho, Sang-Kyu Lee +15 more · 2016 · Nature chemical biology · Nature · added 2026-04-24

Pu-Hyeon Cha, Yong-Hee Cho, Sang-Kyu Lee, JaeHeon Lee, Woo-Jeong Jeong, Byoung-San Moon, Ji-Hye Yun, Jee Sun Yang, Sooho Choi, Juyong Yoon, Hyun-Yi Kim, Mi-Yeon Kim, Saluja Kaduwal, Weontae Lee, Do Sik Min, Hoguen Kim, Gyoonhee Han, Kang-Yell Choi Show less

Both the Wnt/β-catenin and Ras pathways are aberrantly activated in most human colorectal cancers (CRCs) and interact cooperatively in tumor promotion. Inhibition of these signaling may therefore be a Show more

Both the Wnt/β-catenin and Ras pathways are aberrantly activated in most human colorectal cancers (CRCs) and interact cooperatively in tumor promotion. Inhibition of these signaling may therefore be an ideal strategy for treating CRC. We identified KY1220, a compound that destabilizes both β-catenin and Ras, via targeting the Wnt/β-catenin pathway, and synthesized its derivative KYA1797K. KYA1797K bound directly to the regulators of G-protein signaling domain of axin, initiating β-catenin and Ras degradation through enhancement of the β-catenin destruction complex activating GSK3β. KYA1797K effectively suppressed the growth of CRCs harboring APC and KRAS mutations, as shown by various in vitro studies and by in vivo studies using xenograft and transgenic mouse models of tumors induced by APC and KRAS mutations. Destabilization of both β-catenin and Ras via targeting axin is a potential therapeutic strategy for treatment of CRC and other type cancers activated Wnt/β-catenin and Ras pathways. Show less

no PDF DOI: 10.1038/nchembio.2103

AXIN1

Genetic polymorphisms in the Wnt/β-catenin pathway genes as predictors of tumor development and survival in patients with hepatitis B virus-associated hepatocellular carcinoma.

Soon Sun Kim, Hyo Jung Cho, Hyun-Young Lee +8 more · 2016 · Clinical biochemistry · Elsevier · added 2026-04-24

Soon Sun Kim, Hyo Jung Cho, Hyun-Young Lee, Ju Han Park, Choong Kyun Noh, Sung Jae Shin, Kee Myung Lee, Byung Moo Yoo, Kwang Jae Lee, Sung Won Cho, Jae Youn Cheong Show less

Wnt/β-catenin signaling has a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). The present study aimed to determine whether genetic variation in the Wnt/β-catenin signaling pathway Show more

Wnt/β-catenin signaling has a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). The present study aimed to determine whether genetic variation in the Wnt/β-catenin signaling pathway is associated with the development and/or progression of HCC and the survival of patients with hepatitis B virus (HBV)-associated HCC. We assessed seven single nucleotide polymorphisms (SNPs) of the AXIN1, AXIN2, CTNNB1, and WNT2 genes in 245 patients with HBV-associated HCC and 483 chronic HBV carriers without HCC. We analyzed the association of each SNP with HCC development or progression and overall survival. The CTNNB1 rs3864004 A allele was associated with a decreased risk of HCC development (P=0.049). Haplotype analysis revealed a significantly higher frequency of CTNNB1 G-A/G-A haplotype at rs3864004 and rs4135385 positions in patients with HCC than in chronic HBV carriers without HCC (P=0.042). The AXIN1 rs1805105 T>C SNP was associated with small tumor size and early tumor stage and the WNT2 rs39315 G allele was associated with advanced tumor stage in HCC. In Kaplan-Meier analysis, carriers of the AXIN1 rs214252 C allele showed longer survival than those with the TT genotype (P=0.020). In multivariate Cox regression analysis, absence of CTNNB1 haplotype A-A at rs3864004 and rs4135385 positions and advanced tumor stage were independent poor predictors of patient survival in patients with HCC. These findings suggest that the genetic polymorphisms in CTNNB1 gene might affect tumor development and survival in patients with HBV-associated HCC. Show less

no PDF DOI: 10.1016/j.clinbiochem.2016.01.025

AXIN1

Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures.

Unnur Styrkarsdottir, Gudmar Thorleifsson, Sigurjon A Gudjonsson +20 more · 2016 · Nature communications · Nature · added 2026-04-24

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 su Show more

Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, represented by rs28377268 (freq. 11.4-22.6%) that associates with reduced spine BMD (P=1.0 × 10(-11), β=-0.09). We also identified a new spine BMD signal in RSPO3, rs577721086 (freq. 6.8%), that associates with increased spine BMD (P=6.6 × 10(-10), β=0.14). Importantly, both variants associate with osteoporotic fractures and affect expression of the PTCH1 and RSPO3 genes that is in line with their influence on BMD and known biological function of these genes. Additional new BMD signals were also found at the AXIN1 and SOST loci and a new lead SNP at the EN1 locus. Show less

📄 PDF DOI: 10.1038/ncomms10129

AXIN1

Fibrates inhibit the apoptosis of Batten disease lymphoblast cells via autophagy recovery and regulation of mitochondrial membrane potential.

Minho Hong, Ki Duk Song, Hak-Kyo Lee +5 more · 2016 · In vitro cellular & developmental biology. Animal · Springer · added 2026-04-24

Minho Hong, Ki Duk Song, Hak-Kyo Lee, SunShin Yi, Yong Seok Lee, Tae-Hwe Heo, Hyun Sik Jun, Sung-Jo Kim Show less

Batten disease (BD; also known as juvenile neuronal ceroid lipofuscinosis) is a genetic disorder inherited as an autosomal recessive trait and is characterized by blindness, seizures, cognitive declin Show more

Batten disease (BD; also known as juvenile neuronal ceroid lipofuscinosis) is a genetic disorder inherited as an autosomal recessive trait and is characterized by blindness, seizures, cognitive decline, and early death resulting from the inherited mutation of the CLN3 gene. Mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, disrupted autophagy, and enhanced apoptosis have been suggested to play a role in BD pathogenesis. Fibrates, a class of lipid-lowering drugs that induce peroxisome proliferator-activated receptor-α (PPAR-α) activation, are the most commonly used PPAR agonists. Assuming that fibrates have a neuroprotective effect, we studied the effects of fibrates, fenofibrate, bezafibrate, and gemfibrozil on apoptosis, depolarization of mitochondrial membrane, and defective autophagy in BD lymphoblast cells. The viability of fibrate-treated BD lymphoblast cells increased to levels of normal lymphoblast cells. In addition, treatment with fibrates inhibited depolarization of mitochondrial membrane potential in BD lymphoblast cells. Defective autophagy in BD lymphoblast cells was normalized when treated with fibrates as indicated by increased acridine orange staining. The recovery of autophagy in BD lymphoblast cells is most likely attributed to the upregulation of autophagy proteins, lysosomal-associated membrane protein 1 (LAMP1), and LC3 I/II, after treatment with fibrates. This study therefore suggests that fibrates may have a therapeutic potential against BD. Show less

no PDF DOI: 10.1007/s11626-015-9979-7

CLN3

Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function.

Gukhan Kim, Rafael Luján, Jochen Schwenk +6 more · 2016 · eLife · added 2026-04-24

Gukhan Kim, Rafael Luján, Jochen Schwenk, Melissa H Kelley, Carolina Aguado, Masahiko Watanabe, Bernd Fakler, James Maylie, John P Adelman Show less

Mouse CA1 pyramidal neurons express apamin-sensitive SK2-containing channels in the post-synaptic membrane, positioned close to NMDA-type (N-methyl-D-aspartate) glutamate receptors. Activated by synap Show more

Mouse CA1 pyramidal neurons express apamin-sensitive SK2-containing channels in the post-synaptic membrane, positioned close to NMDA-type (N-methyl-D-aspartate) glutamate receptors. Activated by synaptically evoked NMDAR-dependent Ca(2+) influx, the synaptic SK2-containing channels modulate excitatory post-synaptic responses and the induction of synaptic plasticity. In addition, their activity- and protein kinase A-dependent trafficking contributes to expression of long-term potentiation (LTP). We have identified a novel synaptic scaffold, MPP2 (membrane palmitoylated protein 2; p55), a member of the membrane-associated guanylate kinase (MAGUK) family that interacts with SK2-containing channels. MPP2 and SK2 co-immunopurified from mouse brain, and co-immunoprecipitated when they were co-expressed in HEK293 cells. MPP2 is highly expressed in the post-synaptic density of dendritic spines on CA1 pyramidal neurons. Knocking down MPP2 expression selectively abolished the SK2-containing channel contribution to synaptic responses and decreased LTP. Thus, MPP2 is a novel synaptic scaffold that is required for proper synaptic localization and function of SK2-containing channels. Show less

📄 PDF DOI: 10.7554/eLife.12637

DLG2

Comparative deletion mapping at 1p31.3-p32.2 implies NFIA responsible for intellectual disability coupled with macrocephaly and the presence of several other genes for syndromic intellectual disability.

Jonathan D J Labonne, Yiping Shen, Il-Keun Kong +3 more · 2016 · Molecular cytogenetics · BioMed Central · added 2026-04-24

Jonathan D J Labonne, Yiping Shen, Il-Keun Kong, Michael P Diamond, Lawrence C Layman, Hyung-Goo Kim Show less

While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microdeletions in the short arm have been documented. More than half of the 1p microdeletion Show more

While chromosome 1 is the largest chromosome in the human genome, less than two dozen cases of interstitial microdeletions in the short arm have been documented. More than half of the 1p microdeletion cases were reported in the pre-microarray era and as a result, the proximal and distal boundaries containing the exact number of genes involved in the microdeletions have not been clearly defined. We revisited a previous case of a 10-year old female patient with a 1p32.1p32.3 microdeletion displaying syndromic intellectual disability. We performed microarray analysis as well as qPCR to define the proximal and distal deletion breakpoints and revised the karyotype from 1p32.1p32.3 to 1p31.3p32.2. The deleted chromosomal region contains at least 35 genes including NFIA. Comparative deletion mapping shows that this region can be dissected into five chromosomal segments containing at least six candidate genes (DAB1, HOOK1, NFIA, DOCK7, DNAJC6, and PDE4B) most likely responsible for syndromic intellectual disability, which was corroborated by their reduced transcript levels in RT-qPCR. Importantly, one patient with an intragenic microdeletion within NFIA and an additional patient with a balanced translocation disrupting NFIA display intellectual disability coupled with macrocephaly. We propose NFIA is responsible for intellectual disability coupled with macrocephaly, and microdeletions at 1p31.3p32.2 constitute a contiguous gene syndrome with several genes contributing to syndromic intellectual disability. Show less

📄 PDF DOI: 10.1186/s13039-016-0234-z

DOCK7

Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma.

Che-Hung Shen, Sun Hye Kim, Sebastian Trousil +12 more · 2016 · Nature medicine · Nature · added 2026-04-24

Che-Hung Shen, Sun Hye Kim, Sebastian Trousil, Dennie T Frederick, Adriano Piris, Ping Yuan, Li Cai, Lei Gu, Man Li, Jung Hyun Lee, Devarati Mitra, David E Fisher, Ryan J Sullivan, Keith T Flaherty, Bin Zheng Show less

The protein kinase B-Raf proto-oncogene, serine/threonine kinase (BRAF) is an oncogenic driver and therapeutic target in melanoma. Inhibitors of BRAF (BRAFi) have shown high response rates and extende Show more

The protein kinase B-Raf proto-oncogene, serine/threonine kinase (BRAF) is an oncogenic driver and therapeutic target in melanoma. Inhibitors of BRAF (BRAFi) have shown high response rates and extended survival in patients with melanoma who bear tumors that express mutations encoding BRAF proteins mutant at Val600, but a vast majority of these patients develop drug resistance. Here we show that loss of stromal antigen 2 (STAG2) or STAG3, which encode subunits of the cohesin complex, in melanoma cells results in resistance to BRAFi. We identified loss-of-function mutations in STAG2, as well as decreased expression of STAG2 or STAG3 proteins in several tumor samples from patients with acquired resistance to BRAFi and in BRAFi-resistant melanoma cell lines. Knockdown of STAG2 or STAG3 expression decreased sensitivity of BRAF(Val600Glu)-mutant melanoma cells and xenograft tumors to BRAFi. Loss of STAG2 inhibited CCCTC-binding-factor-mediated expression of dual specificity phosphatase 6 (DUSP6), leading to reactivation of mitogen-activated protein kinase (MAPK) signaling (via the MAPKs ERK1 and ERK2; hereafter referred to as ERK). Our studies unveil a previously unknown genetic mechanism of BRAFi resistance and provide new insights into the tumor suppressor function of STAG2 and STAG3. Show less

📄 PDF DOI: 10.1038/nm.4155

DUSP6

Adjuvant Trametinib Delays the Outgrowth of Occult Pancreatic Cancer in a Mouse Model of Patient-Derived Liver Metastasis.

Timothy E Newhook, James M Lindberg, Sara J Adair +5 more · 2016 · Annals of surgical oncology · added 2026-04-24

Timothy E Newhook, James M Lindberg, Sara J Adair, Alison J Kim, Edward B Stelow, Osama E Rahma, J Thomas Parsons, Todd W Bauer Show less

Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 5 years following resection plus adjuvant gemcitabine (Gem) from outgrowth of occult metastases. We hypothesized that inhibition o Show more

Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 5 years following resection plus adjuvant gemcitabine (Gem) from outgrowth of occult metastases. We hypothesized that inhibition of the KRAS pathway with the MEK inhibitor trametinib would inhibit the outgrowth of occult liver metastases in a preclinical model. Liver metastases harvested from two patients with PDAC (Tumors 608, 366) were implanted orthotopically in mice. Tumor cell lines were derived and transduced with lentiviruses encoding luciferase and injected into spleens of mice generating microscopic liver metastases. Growth kinetics of liver metastases were measured with bioluminescent imaging and time-to-progression (TTP), progression-free survival (PFS), and overall survival (OS) were determined. Trametinib (0.3 mg/kg BID) significantly prolonged OS versus control (Tumor 608: 114 vs. 43 days, p < 0.001; Tumor 366: not reached vs. 167 days, p = 0.0488). In vivo target validation demonstrated trametinib significantly reduced phosphorylated-ERK and expression of the ERK-responsive gene DUSP6. In a randomized, preclinical trial, mice were randomized to: (1) control, (2) adjuvant Gem (100 mg/kg IP, Q3 days) × 7 days followed by surveillance, or (3) adjuvant Gem followed by trametinib. Sequential Gem-trametinib significantly decreased metastatic cell outgrowth and increased TTP and PFS. Treatment of mice bearing micrometastases with trametinib significantly delayed tumor outgrowth by effectively inhibiting KRAS-MEK-ERK signaling. In a randomized, preclinical, murine trial adjuvant sequential Gem followed by trametinib inhibited occult metastatic cell outgrowth in the liver and increased PFS versus adjuvant Gem alone. An adjuvant trial of sequential Gem-trametinib is being planned in patients with resected PDAC. Show less

📄 PDF DOI: 10.1245/s10434-016-5116-4

DUSP6

Alternative splicing generates novel Fads3 transcript in mice.

Ji Yao Zhang, Xia Qin, Hui Gyu Park +4 more · 2016 · Molecular biology reports · Springer · added 2026-04-24

Ji Yao Zhang, Xia Qin, Hui Gyu Park, Ellen Kim, Guowen Liu, Kumar S D Kothapalli, J Thomas Brenna Show less

Fads3 is the third member of the fatty acid desaturase gene cluster; with at least eight evolutionarily conserved alternative transcripts (AT), having no clearly established function as are known for Show more

Fads3 is the third member of the fatty acid desaturase gene cluster; with at least eight evolutionarily conserved alternative transcripts (AT), having no clearly established function as are known for FADS2 and FADS1. Here we present identification of a novel Fads3 transcript in mice (Fads3AT9), characterize Fads3AT9 expression in mouse tissues and evaluate correlations with metabolite profiles. Total RNA obtained from mouse tissues is reverse-transcribed into cDNA and used as template for PCR reactions. Tissue fatty acids were extracted and quantified by gas chromatography. Sequencing analysis revealed complete absence of exon 2 resulting in an open reading frame of 1239 bp, encoding a putative protein of 412 aa with loss of 37 aa compared to classical Fads3 (Fads3CS). FADS3AT9 retains all the conserved regions characteristic of front end desaturase (cytochrome b5 domain and three histidine repeats). Both Fads3CS and Fads3AT9 are ubiquitously expressed in 11 mouse tissues. Fads3AT9 abundance was greater than Fads3CS in pancreas, liver, spleen, brown adipose tissue and thymus. Fads3CS expression is low in pancreas while Fads3AT9 is over ten-fold greater abundance. The eicosanoid precursor fatty acid 20:4n - 6, the immediate desaturation product of the Fads1 coded Δ5-desaturase, was highest in pancreas where Fads3CS is low. Changes in expression patterns and fatty acid profiles suggest that Fads3AT9 may play a role in the regulation and/or biosynthesis of long chain polyunsaturated fatty acids from precursors. Show less

📄 PDF DOI: 10.1007/s11033-016-4018-7

FADS1

Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci.

Clint L Miller, Milos Pjanic, Ting Wang +17 more · 2016 · Nature communications · Nature · added 2026-04-24

Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies have identified > Show more

Coronary artery disease (CAD) is the leading cause of mortality and morbidity, driven by both genetic and environmental risk factors. Meta-analyses of genome-wide association studies have identified >150 loci associated with CAD and myocardial infarction susceptibility in humans. A majority of these variants reside in non-coding regions and are co-inherited with hundreds of candidate regulatory variants, presenting a challenge to elucidate their functions. Herein, we use integrative genomic, epigenomic and transcriptomic profiling of perturbed human coronary artery smooth muscle cells and tissues to begin to identify causal regulatory variation and mechanisms responsible for CAD associations. Using these genome-wide maps, we prioritize 64 candidate variants and perform allele-specific binding and expression analyses at seven top candidate loci: 9p21.3, SMAD3, PDGFD, IL6R, BMP1, CCDC97/TGFB1 and LMOD1. We validate our findings in expression quantitative trait loci cohorts, which together reveal new links between CAD associations and regulatory function in the appropriate disease context. Show less

📄 PDF DOI: 10.1038/ncomms12092

LMOD1

Microtubule-Actin Crosslinking Factor 1 Is Required for Dendritic Arborization and Axon Outgrowth in the Developing Brain.

Minhan Ka, Woo-Yang Kim · 2016 · Molecular neurobiology · Springer · added 2026-04-24

Dendritic arborization and axon outgrowth are critical steps in the establishment of neural connectivity in the developing brain. Changes in the connectivity underlie cognitive dysfunction in neurodev Show more

Dendritic arborization and axon outgrowth are critical steps in the establishment of neural connectivity in the developing brain. Changes in the connectivity underlie cognitive dysfunction in neurodevelopmental disorders. However, molecules and associated mechanisms that play important roles in dendritic and axon outgrowth in the brain are only partially understood. Here, we show that microtubule-actin crosslinking factor 1 (MACF1) regulates dendritic arborization and axon outgrowth of developing pyramidal neurons by arranging cytoskeleton components and mediating GSK-3 signaling. MACF1 deletion using conditional mutant mice and in utero gene transfer in the developing brain markedly decreased dendritic branching of cortical and hippocampal pyramidal neurons. MACF1-deficient neurons showed reduced density and aberrant morphology of dendritic spines. Also, loss of MACF1 impaired the elongation of callosal axons in the brain. Actin and microtubule arrangement appeared abnormal in MACF1-deficient neurites. Finally, we found that GSK-3 is associated with MACF1-controlled dendritic differentiation. Our findings demonstrate a novel role for MACF1 in neurite differentiation that is critical to the creation of neuronal connectivity in the developing brain. Show less

📄 PDF DOI: 10.1007/s12035-015-9508-4

MACF1

BIX02189 inhibits TGF-β1-induced lung cancer cell metastasis by directly targeting TGF-β type I receptor.

Seong Ji Park, Yu Sun Choi, Seungkoo Lee +4 more · 2016 · Cancer letters · Elsevier · added 2026-04-24

Seong Ji Park, Yu Sun Choi, Seungkoo Lee, Young Jae Lee, Suntaek Hong, Sanghwa Han, Byung-Chul Kim Show less

Transforming growth factor-β1 (TGF-β1) promotes tumor metastasis by inducing an epithelial-to-mesenchymal transition (EMT) in cancer cells. In this study, we investigated the effects of BIX02189 and X Show more

Transforming growth factor-β1 (TGF-β1) promotes tumor metastasis by inducing an epithelial-to-mesenchymal transition (EMT) in cancer cells. In this study, we investigated the effects of BIX02189 and XMD8-92, pharmacologic inhibitors of the MEK5 [mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK)5] signaling pathway, on the EMT and migration of cancer cells induced by TGF-β1. In human A549 lung cancer cells, TGF-β1-induced EMT, cell motility, and expression of matrix metalloproteinase-2 were completely inhibited by BIX02189, but not by XMD8-92 or small interference RNAs specific to MEK5 and ERK5. Interestingly, BIX02189 strongly blocked the activation of TGF-β1 signaling components, and this inhibitory effect was not reproduced by MEK5 inhibition. Molecular docking simulation and kinase assays revealed that BIX02189 binds directly to the ATP-binding site of the TGF-β receptor type I (TβRI) and suppresses its kinase activity. Finally, the anti-metastatic effect of BIX02189 was validated in a TβRI-derived A549 xenograft mouse model. Collectively, these findings newly characterize BIX02189 as a potent inhibitor of TβRI that can block the tumor metastatic activity of TGF-β1. Show less

no PDF DOI: 10.1016/j.canlet.2016.08.010

MAP2K5

Acute Myeloid Leukemia With MLL Rearrangement and CD4+/CD56+ Expression can be Misdiagnosed as Blastic Plasmacytoid Dendritic Cell Neoplasm: Two Case Reports.

Ju Mee Lee, In Suk Kim, Jeong Nyeo Lee +7 more · 2016 · Annals of laboratory medicine · added 2026-04-24

Ju Mee Lee, In Suk Kim, Jeong Nyeo Lee, Sang Hyuk Park, Hyung Hoi Kim, Chulhun L Chang, Eun Yup Lee, Hye Ran Kim, Seung Hwan Oh, Sae Am Song Show less

📄 PDF DOI: 10.3343/alm.2016.36.5.494

MLLT10

👤 Dan Say Kim