PML mimics EBNALP’s functional profile in co-activation with EBNA2

• Main Authors: Hsin-lin Tsai, 蔡欣霖
• Other Authors: Chih-Wen Peng
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/34169079631795771877

碩士 === 慈濟大學 === 生命科學系碩士班 === 99 === Epstein-Barr Virus (EBV) Nuclear antigen 2 (EBNA2) and leader protein (LP) are essential for immortalization of B lymphocytes upon EBV infection. EBNA2 acts as a transcription activator both viral and cellular genes, whereas EBNALP augments the transcription mediated by EBNA2. In the previous study, EBNALP was shown to localize at promyelocytic leukaemia (PML) nuclear bodies (NB), however, the function of EBNALP at PML NBs remains unclear. PML has been implicated in cell growth control, tumor suppression, apoptosis, and transcriptional regulation. In this study, we attempt to explore the potential role of PML in EBNA2 mediated transcription. Although Ling’s group has demonstrated that PML3 is unable to co-activate EBNA2, we found that one of PML isoforms, PML-L, can efficiently co-activate with EBNA2 without EBNALP. Dissimilar to PML3, PML-L can mimic EBNALP to function as a transcription co-activator of EBNA2. In addition, the interaction of EBNA2 with PML-L in vivo was demonstrated by BiFC assay. We found the conserved RBCC domain of PML is sufficient to co-activate EBNA2. Of importance, the co-activating effect of PML on EBNA2 was strongly abrogated when the SUMOylation residue Lysine160 was replaced by either alanine or arginine. SUMOylation of Lysine160 is known to be essential for PML NBs formation. This evidence suggests the formation of PML NBs plays an important role in PML co-activation with EBNA2. Yet another important discovery is that the unique region of PML3 C-terminus can exert a robust repressing effect to suppress the function of PML co-activating domain (RBCC domain). Our current data lead us to propose a model by which the RBCC domain of PML is able to mimic EBNALP co-activation with EBNA2.