Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA.
Virology. 2014 Jan 5;448:293-302. doi: 10.1016/j.virol.2013.10.018. Epub 2013 Nov 8.
Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly expressed during malignancies. We recently documented that Epstein-Barr virus (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma-associated herpesvirus (KSHV) infection induced UCH-L1 expression, via cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jκ and activation of the uch-l1 promoter. UCH-L1 expression was also increased in Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products expressed in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1 expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1 expression. These results indicate that viral latency products of both human γ-herpesviruses contribute to uch-l1 expression, which may contribute to the progression of lymphoid malignancies.
泛素 C 端水解酶 L1（UCH-L1）具有致癌特性，在恶性肿瘤中高度表达。我们最近的研究表明，EB 病毒（EBV）感染会诱导 uch-l1 的表达。在这里，我们发现卡波济肉瘤相关疱疹病毒（KSHV）感染通过 KSHV 潜伏相关核抗原（LANA）和 RBP-Jκ的合作以及 uch-l1 启动子的激活诱导 UCH-L1 的表达。与仅感染 KSHV 的原发性渗出性淋巴瘤（PEL）细胞相比，同时感染 KSHV 和 EBV 的 PEL 细胞中UCH-L1 的表达也增加，这表明 EBV 增强了 LANA 对 uch-l1 的作用。EBV 潜伏膜蛋白 1（LMP1）是 PEL 细胞中表达的少数 EBV 产物之一。结果表明，LMP1 足以诱导 uch-l1 的表达，并且 LMP1 和 LANA 的共表达对 uch-l1 的表达有相加作用。这些结果表明，两种人类 γ 疱疹病毒的病毒潜伏产物均有助于 uch-l1 的表达，这可能有助于淋巴恶性肿瘤的进展。
