👤 Osamu Takeichi

Epstein-Barr virus (EBV) is an enveloped, double-stranded DNA virus that selectively infects primates. Periodontitis, a common inflammatory disease characterized by alveolar bone destruction, affects more than half of the global adult population. While EBV has been linked to periodontitis due to its pro-inflammatory effects and presence in the human periodontium, its effects on bone metabolism, particularly alveolar bone resorption, remain unclear. This study demonstrated that EBV infection in humanized mice induced osteoclast differentiation and alveolar bone resorption, resulting in sparse trabecular bone patterns and increased lacunae resorption. Extracellular vesicles (EVs) from EBV-infected cells contained M-CSF, essential for osteoclast differentiation, and increased CTSK and RANKL expression in osteoclast precursor cells after uptake. EBV infection increased the expression of group IIA-secreted phospholipase A Show less

The yeast E2F functional homologs MBF (Mbp1/Swi6) and SBF (Swi4/Swi6) complexes are critical transcription factors for G1/S transition. The target of rapamycin complex 1 (TORC1) kinase promotes G1/S transition via upregulation of the G1 cyclin Cln3 that activates MBF and SBF in favorable nutrient conditions. Here, we show evidence that TORC1 directly regulates G1/S transition via MBF and SBF. Various proteins involved in G1/S transition, including Mbp1 and Swi4, but not Swi6, were largely lost after rapamycin treatment. TORC1 inactivation facilitated degradation of Mbp1 and Swi4. Mbp1 degradation was dependent on Skp1-Cullin1-F-box (SCF)-Grr1 and proteasomes. We identified a PEST-like degron in Mbp1. Mutant cells with an unstable Mbp1 protein were hypersensitive to rapamycin and more accumulated G1 cells in the absence and presence of rapamycin. This study revealed that TORC1 directly controls MBF/SBF-mediated G1/S transition in response to nutrient availability. Show less