title: A new layer of degradation mechanism for PR-Set7/Set8 during cell cycle.
abstract: Set8 is critically involved in transcription regulation, cell cycle progression and genomic stability. Emerging evidence has revealed that E3 ubiquitin ligases such as CRL4cdt2and SCFSkp2regulate 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 SCFβ-TRCPcomplex regulates Set8 protein stability by targeting it for ubiquitination and subsequent degradation. Notably, Set8 interacts with the SCFβ-TRCPE3 ligase complex. We further revealed a critical role of CKI in SCFβ-TRCP-mediated degradation of Set8. Mechanistically, CKI-mediated phosphorylation of Set8 at the S253 site promotes its destruction by SCFβ-TRCP. Importantly, SCFβ-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 β-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.
authors.affiliation: a The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University , Suzhou , P. R. China.
authors.forename: Nana
authors.initials: N
authors.lastname: Zheng
authors.affiliation: b Department of Pathology , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Dai
authors.affiliation: a The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University , Suzhou , P. R. China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: b Department of Pathology , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D002453:Cell Cycle; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D059748:Proteolysis; D044844:beta-Transducin Repeat-Containing Proteins / Q000378:metabolism
chemical_list: D044844:beta-Transducin Repeat-Containing Proteins; D011495:Histone-Lysine N-Methyltransferase
keywords: Cell cycle; DNA damage; Set8; Ubiquitin; cell proliferation; β-TRCP