USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1
作者： Xinna Zhang , Franklin G Berger , Jianhua Yang , Xiongbin Lu
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摘要: Tumour suppressor p53 levels in the cell are tightly regulated by controlled degradation through ubiquitin ligases including Mdm2, COP1, Pirh2, and ARF-BP1. The ubiquitination process is reversible via deubiquitinating enzymes, such as ubiquitin-specific peptidases (USPs). In this study, we identified peptidase 4 (USP4) an important regulator of p53. USP4 interacts directly with deubiquitinates ARF-BP1, leading to stabilization ARF-BP1 subsequent reduction levels. Usp4 knockout mice viable developmentally normal, but showed enhanced apoptosis thymus spleen response ionizing radiation. Compared wild-type mouse embryonic fibroblasts (MEFs), Usp4−/− MEFs exhibited retarded growth, premature cellular senescence, resistance oncogenic transformation, hyperactive DNA damage checkpoints, consistent upregulated activity absence USP4. Finally, that overexpressed several types human cancer, suggesting a potential oncogene.
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