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CyclinB/cdk1‐mediated phosphorylation of the PR‐Set7 histone methyltransferase is required for its nuclear localization and stability during mitosis
Author(s) -
Wu Shumin,
Rice Judd C.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.514.1
Subject(s) - mitosis , microbiology and biotechnology , chromatin , phosphorylation , cyclin dependent kinase 1 , biology , histone , cell cycle , chemistry , biochemistry , cell , dna
We previously demonstrated that accumulation of PR‐Set7 and the histone modification that it creates, monomethyl‐H4K20, during G2/M are essential for mammalian cell cycle progression. However, it remains unclear how PR‐Set7 protein is regulated during mitosis. Based on recent findings, we hypothesized that PR‐Set7 is a mitotic phosphoprotein and that this phosphorylation event affects PR‐Set7 function during mitosis. Here we discovered that human PR‐Set7 is phosphorylated specifically by cyclinB/cdk1 and exclusively at G2/M. We found that PR‐Set7 phosphorylation occurs early during mitosis and that this event is required for the proper localization of PR‐Set7 within the nucleus. In addition, phosphorylation stabilizes PR‐Set7 protein levels by directly preventing its ubiquitination and proteasome‐mediated degradation. Importantly, impairment of PR‐Set7 function resulted in global chromatin decondensation, cell cycle and segregation defects. Collectively, our results reveal a novel mechanism by which cyclinB/cdk1‐mediated phosphorylation of PR‐Set7 functions to stabilize and direct this chromatin‐modifying enzyme to ensure normal cell division.