期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 46, 页码 39021-39029出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.390328
关键词
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资金
- Lerner Research Institute
Ubiquitin-mediated proteolysis is a key regulatory process in cell cycle progression. The Skp1-Cul1-F-box (SCF) and anaphase-promoting complex (APC) ubiquitin ligases target numerous components of the cell cycle machinery for destruction. Throughout the cell cycle, these ligases cooperate to maintain precise levels of key regulatory proteins, and indirectly, each other. Recently, we have identified the deubiquitinase USP37 as a regulator of the cell cycle. USP37 expression is cell cycle-regulated, being expressed in late G(1) and ubiquitinated by APC(Cdh1) in early G(1). Here we report that in addition to destruction at G(1), a major fraction of USP37 is degraded at the G(2)/M transition, prior to APC substrates and similar to SCF beta TrCP substrates. Consistent with this hypothesis, USP37 interacts with components of the SCF in a beta TrCP-dependent manner. Interaction with beta TrCP and subsequent degradation is phosphorylation-dependent and is mediated by the Polo-like kinase (Plk1). USP37 is stabilized in G(2) by depletion of beta TrCP as well as chemical or genetic manipulation of Plk1. Similarly, mutation of the phospho-sites abolishes beta TrCP binding and renders USP37 resistant to Plk1 activity. Expression of this mutant hinders the G(2)/M transition. Our data demonstrate that tight regulation of USP37 levels is required for proper cell cycle progression.
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