Ubiquitin-dependent and -independent proteasomal degradation of hepatitis B virus X protein
Ubiquitin-dependent and -independent proteasomal degradation of hepatitis B virus X protein
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DOI：
10.1016/j.bbrc.2007.12.070
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发表时间：
2008-02-22
影响因子：
3.1
通讯作者：
Ahn, Byung-Yoon
中科院分区：
文献类型：
--
作者：
Kim, Jung-Hwan;Sohn, Sook-Young;Ahn, Byung-Yoon
乙肝病毒X蛋白(HBx)在病毒复制和肝细胞癌的发生发展中起着关键的调节作用。HBx是一种不稳定的蛋白质；它的不稳定归因于通过泛素-蛋白酶体途径的快速降解。在这里，我们表明，HBx的中间和羧基末端结构域独立地与GFP融合，使重组蛋白对蛋白酶体降解敏感，而氨基末端结构域对HBx的泛素化或稳定性几乎没有影响。六个赖氨酸残基中的任何一个或最多五个的组合突变，都位于中间和羧基末端结构域，并没有阻止HBx泛素化，排除了任何特定的赖氨酸作为泛素化的唯一位点。令人惊讶的是，HBX中所有六种赖氨酸都发生了突变，并且没有显示出泛素化的证据，仍然容易受到蛋白酶体降解的影响。这些结果表明，泛素依赖和非依赖的蛋白酶体降解过程都在HBx周转中起作用。(C)2007 Elsevier Inc.保留所有权利。
The hepatitis B virus X protein (HBX) plays key regulatory roles in viral replication and the development of hepatocellular carcinoma. HBX is an unstable protein; its instability is attributed to rapid degradation through the ubiquitin-proteasome pathway. Here, we show that the middle and carboxyl-terminal domains of HBX, independently fused to GFP, render the recombinant proteins susceptible to proteasomal degradation, while the amino-terminal domain has little effect on the ubiquitination or stability of HBX. Mutation of any single or combination of up to five of six lysine residues, all located in the middle and carboxyl-terminal domain, did not prevent HBX from being ubiquitinated, ruling out any specific lysine as the sole site of ubiquitination. Surprisingly, HBX in which all six lysines were mutated and showed no evidence of ubiquitination, was still susceptible to proteasomal degradation. These results suggest that both ubiquitin-dependent and -independent proteasomal degradation processes are operative in HBX turnover. (c) 2007 Elsevier Inc. All rights reserved.