Modification of papillomavirus E2 proteins by the small ubiquitin-like modifier family members (SUMOs).
Modification of papillomavirus E2 proteins by the small ubiquitin-like modifier family members (SUMOs).
复制标题
DOI：
10.1016/j.virol.2008.06.008
复制
发表时间：
2008-09-01
期刊：
影响因子：
3.7
通讯作者：
Wilson, Van G.
中科院分区：
文献类型：
--
作者：
Wu, Yu-Chieh;Roark, Ashley A.;Bian, Xue-Lin;Wilson, Van G.
乳头瘤病毒E2蛋白是在复制、基因组分离和病毒转录中起作用的关键调节蛋白，包括控制病毒癌基因E6和E7的表达。类小泛素化是一种翻译后修饰，已被证明可以靶向和调节许多转录因子的功能，我们现在证明E2蛋白是类小泛素化的。牛和人乳头瘤病毒E2蛋白均与SUMO结合酶Ubc 9结合，并使用体外和E. coli SUMO化系统中，这些E2蛋白很容易被SUMO蛋白修饰。体内实验进一步证实E2可以被SUMO 1、SUMO 2或SUMO 3类小泛素化。定位研究确定赖氨酸292作为SUMO与HPV 16 E2共价结合的主要残基，并且赖氨酸292至精氨酸突变体显示出转录激活和抑制的缺陷。HPV16 E2的表达水平、细胞内定位和DNA结合活性均未被K292R突变所改变，这表明转录缺陷反映了该残基处sumoylation的功能贡献。这项研究提供了证据，sumoylation在调节乳头瘤病毒E2的作用，并确定了一个新的机制，在翻译后水平的E2功能的调制。
Papillomavirus E2 proteins are critical regulatory proteins that function in replication, genome segregation, and viral transcription, including control of expression of the viral oncogenes, E6 and E7. Sumoylation is a post-translational modification that has been shown to target and modulate the function of many transcription factors, and we now demonstrate that E2 proteins are sumoylated. Both bovine and human papillomavirus E2 proteins bind to the SUMO conjugation enzyme, Ubc9, and using in vitro and E. coli sumoylation systems, these E2 proteins were readily modified by SUMO proteins. In vivo experiments further confirmed that E2 can be sumoylated by SUMO1, SUMO2, or SUMO3. Mapping studies identified lysine 292 as the principal residue for covalent conjugation of SUMO to HPV16 E2, and a lysine 292 to arginine mutant showed defects for both transcriptional activation and repression. The expression levels, intracellular localization, and the DNA-binding activity of HPV16 E2 were unchanged by this K292R mutation, suggesting that the transcriptional defect reflects a functional contribution by sumoylation at this residue. This study provides evidence that sumoylation has a role in the regulation of papillomavirus E2, and identifies a new mechanism for the modulation of E2 function at the post-translational level.
登录
查看更多内容
影响因子：
4.8
作者：
Chang, LK;Lee, YH;Liu, ST
通讯作者：
Liu, ST
影响因子：
5.4
作者：
Benson, JD;Lawande, R;Howley, PM
通讯作者：
Howley, PM
影响因子：
5.4
作者：
CHIANG, CM;DONG, G;CHOW, LT
通讯作者：
CHOW, LT
影响因子：
4.8
作者：
Goodson, ML;Hong, Y;Sarge, KD
通讯作者：
Sarge, KD
影响因子：
10.5
作者：
HIROCHIKA, H;HIROCHIKA, R;CHOW, LT
通讯作者：
CHOW, LT