Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry.

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Citation

Huang X, Summers MK, Pham V, Lill JR, Liu J, Lee G, Kirkpatrick DS, Jackson PK, Fang G, Dixit VM

Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry.

Mol Cell. 2011 May 20;42(4):511-23. doi: 10.1016/j.molcel.2011.03.027.

PubMed ID
21596315 [ View in PubMed
]
Abstract

Cell cycle progression requires the E3 ubiquitin ligase anaphase-promoting complex (APC/C), which uses the substrate adaptors CDC20 and CDH1 to target proteins for proteasomal degradation. The APC(CDH1) substrate cyclin A is critical for the G1/S transition and, paradoxically, accumulates even when APC(CDH1) is active. We show that the deubiquitinase USP37 binds CDH1 and removes degradative polyubiquitin from cyclin A. USP37 was induced by E2F transcription factors in G1, peaked at G1/S, and was degraded in late mitosis. Phosphorylation of USP37 by CDK2 stimulated its full activity. USP37 overexpression caused premature cyclin A accumulation in G1 and accelerated S phase entry, whereas USP37 knockdown delayed these events. USP37 was inactive in mitosis because it was no longer phosphorylated by CDK2. Indeed, it switched from an antagonist to a substrate of APC(CDH1) and was modified with degradative K11-linked polyubiquitin.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Cyclin-dependent kinase 2P24941Details
Cyclin-A2P20248Details