Cdc34-mediated degradation of ATF5 is blocked by cisplatin.

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Citation

Wei Y, Jiang J, Liu D, Zhou J, Chen X, Zhang S, Zong H, Yun X, Gu J

Cdc34-mediated degradation of ATF5 is blocked by cisplatin.

J Biol Chem. 2008 Jul 4;283(27):18773-81. doi: 10.1074/jbc.M707879200. Epub 2008 May 5.

PubMed ID
18458088 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Cyclic AMP-dependent transcription factor ATF-5Q9Y2D1Details