Viral oncoprotein LMP1 disrupts p53-induced cell cycle arrest and apoptosis through modulating K63-linked ubiquitination of p53

摘要: Disruption of the gatekeeper p53 tumor suppressor is involved in various virus-associated tumorigeneses, with aberrant ubiquitination as major cause abnormalities tumors. Of note, wild-type accumulated Epstein-Barr virus (EBV)-associated tumors, especially nasopharyngeal carcinoma (NPC). We have previously identified that and phosphorylated by EBV oncoprotein latent membrane protein 1 (LMP1) NPC. Here, we further found LMP1 promoted accumulation via two distinct ubiquitin modifications. stability suppressing K48-linked mediated E3 ligase MDM2, which associated its phosphorylation at Ser20, while increasing levels total cellular ubiquitinated p53. also induced K63-linked interacting necrosis factor receptor-associated 2 (TRAF2), thus contributing to accumulation. Furthermore, rescued cell apoptosis cycle arrest Collectively, these results demonstrate modifications biological functions viral LMP1, has broad implications pathogenesis multiple EBV-associated