科研之友
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摘要
Set8 is critically involved in transcription regulation, cell cycle progression and genomic stability. Emerging evidence has revealed that E3 ubiquitin ligases such as CRL4cdt2 and SCFSkp2 regulate Set8 protein abundance. However, it is unclear whether other E3 ligase(s) could govern Set8 level for proper cell cycle progression in response to genotoxic stress such as UV irradiation. Recently, we report that the SCF beta-TRCP complex regulates Set8 protein stability by targeting it for ubiquitination and subsequent degradation. Notably, Set8 interacts with the SCF beta-TRCP E3 ligase complex. We further revealed a critical role of CKI in SCF beta-TRCP-mediated degradation of Set8. Mechanistically, CKI-mediated phosphorylation of Set8 at the S253 site promotes its destruction by SCF beta-TRCP. Importantly, SCF beta-TRCP-dependent Set8 destruction also contributes to the tight control of cell proliferation and cell cycle progression, in response to UV irradiation. Here, we summarize our new findings regarding the crucial role of beta-TRCP in CKI-mediated Set8 degradation, which could provide new evidence to support that dysregulation of a tight regulatory network of Set8 could lead to aberrant cell cycle process.
- 出版日期2016
- 单位苏州大学
