In this study, we investigated the intricate mechanisms underlying thrombin and Ang II-induced depletion of ABCA1. Under basal conditions, the COP9 signalosome interacts with ABCA1 as a whole complex Show more
In this study, we investigated the intricate mechanisms underlying thrombin and Ang II-induced depletion of ABCA1. Under basal conditions, the COP9 signalosome interacts with ABCA1 as a whole complex rather than as individual subunits. In the presence of GPCR-agonists, thrombin or angiotensin II (Ang II), ABCA1 was phosphorylated and dissociated from COP9 signalosome, paving the way for its cullin3-mediated ubiquitination and degradation. Furthermore, forced expression of CSN5, the catalytic core subunit of the COP9 signalosome, inhibited thrombin or Ang II-induced ubiquitination and degradation of ABCA1, thereby restoring cholesterol efflux and suppressing foam cell formation. In addition, xanthine oxidase-dependent H Show less
Impaired cholesterol efflux and/or uptake can influence arterial lipid accumulation leading to atherosclerosis. Here, we report that tripartite motif-containing protein 13 (TRIM13), a RING-type E3 ubi Show more
Impaired cholesterol efflux and/or uptake can influence arterial lipid accumulation leading to atherosclerosis. Here, we report that tripartite motif-containing protein 13 (TRIM13), a RING-type E3 ubiquitin ligase, plays a role in arterial lipid accumulation leading to atherosclerosis. Using molecular approaches and KO mouse model, we found that TRIM13 expression was induced both in the aorta and peritoneal macrophages (pMφ) of ApoE Show less