Cdc34-mediated Degradation of ATF5 Is Blocked by Cisplatin*
Cdc34-mediated Degradation of ATF5 Is Blocked by Cisplatin*
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DOI：
10.1074/jbc.m707879200
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发表时间：
2008-07
影响因子：
4.8
通讯作者：
Yuanyan Wei;Jianhai Jiang;Dan Liu;Jin Zhou;Xiaoning Chen;Si Zhang;H. Zong;Xiao-jing Yun;J. Gu
中科院分区：
文献类型：
--
作者：
Yuanyan Wei;Jianhai Jiang;Dan Liu;Jin Zhou;Xiaoning Chen;Si Zhang;H. Zong;Xiao-jing Yun;J. Gu
ATF5, a member of activating transcription factor (ATF)/cAMP-response element-binding protein (CREB) family of b-ZIP transcription factors, contributes to neural cell differentiation and is involved in cell apoptosis in response to cisplatin and a number of environment factors. However, the mechanisms governing the regulation of ATF5 protein during apoptosis are largely unknown. In this study we reported that ATF5 protein was a substrate of the ubiquitin-proteasome pathway. Interestingly, the ubiquitin-dependent degradation of exogenous ATF5 protein was independent of lysine residues. Instead, the addition of a large N-terminal enhanced green fluorescence protein tag increased the stability of ATF5 protein, and the free amino acid group of the N-terminal methionine of ATF5 protein was a site for ubiquitinylation, indicating that exogenous ATF5 was degraded via the ubiquitin-proteasome system through N-terminal ubiquitinylation. Furthermore, cisplatin increased ATF5 protein expression via preventing its ubiquitin-dependent degradation, which might be associated with its promoting the nucleus-to-cytoplasm translocation of E2 ubiquitin-conjugating enzyme Cdc34 and reducing the interaction between ATF5 and Cdc34. In summary, a down-regulation of proteasome-mediated degradation of ATF5 might contribute to cisplatin-induced apoptosis, providing a new mechanism of cisplatin-induced apoptosis.
