Hong Seung-Woo, Kim Seung-Mi, Jin Dong-Hoon, Kim Yeong Seok, Hur Dae Young
Department of Anatomy and Tumor Immunology, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Pusan 47392, Republic of Korea.
Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2017 Sep 16;491(2):303-309. doi: 10.1016/j.bbrc.2017.07.105. Epub 2017 Jul 20.
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is an oncoviral protein that plays a pivotal role in EBV-induced oncogenic transformation. The function of LMP1 in EBV-induced oncogenesis has been well studied. However, the molecular mechanisms underlying LMP1 protein stability remain poorly understood. In this study, we found that ribosomal protein s27a (RPS27a) regulates LMP1 stability by a tandem affinity purification analysis. RPS27a interacts directly with LMP1 in vitro and in vivo. Furthermore, overexpression of RPS27a increases the half-life of LMP1 in 293T cells, whereas downregulation of RPS27a using lentiviral shRNA technology accelerates the decrease in LMP1 protein level in EBV-transformed B cells. We show that LMP1 ubiquitination via the proteasome is completely inhibited by overexpression of RPS27a. RPS27a also enhances LMP1-mediated proliferation and invasion, suggesting that RPS27a interacts with LMP1 and stabilizes it by suppressing proteasome-mediated ubiquitination. These results suggest that RSP27a could be a potential target in EBV-infected LMP1-positive cancer cells.
爱泼斯坦-巴尔病毒（EBV）编码的潜伏膜蛋白1（LMP1）是一种肿瘤病毒蛋白，在EBV诱导的致癌转化中起关键作用。LMP1在EBV诱导的肿瘤发生中的功能已得到充分研究。然而，LMP1蛋白稳定性的分子机制仍知之甚少。在本研究中，我们通过串联亲和纯化分析发现核糖体蛋白s27a（RPS27a）调节LMP1的稳定性。RPS27a在体外和体内均直接与LMP1相互作用。此外，RPS27a的过表达增加了293T细胞中LMP1的半衰期，而使用慢病毒shRNA技术下调RPS27a则加速了EBV转化的B细胞中LMP1蛋白水平的下降。我们表明，RPS27a的过表达完全抑制了通过蛋白酶体的LMP1泛素化。RPS27a还增强了LMP1介导的增殖和侵袭，表明RPS27a与LMP1相互作用并通过抑制蛋白酶体介导的泛素化使其稳定。这些结果表明，RSP27a可能是EBV感染的LMP1阳性癌细胞中的一个潜在靶点。
