title: Deubiquitinase USP37 is activated by CDK2 to antagonize APC(CDH1) and promote S phase entry.
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.
authors: Department of Physiological Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors: Xiaodong
authors: X
authors: Huang
authors: Matthew K
authors: MK
authors: Summers
authors: Victoria
authors: V
authors: Pham
authors: Jennie R
authors: JR
authors: Lill
authors: Jinfeng
authors: J
authors: Liu
authors: Gwanghee
authors: G
authors: Lee
authors: Donald S
authors: DS
authors: Kirkpatrick
authors: Peter K
authors: PK
authors: Jackson
authors: Guowei
authors: G
authors: Fang
authors: Vishva M
authors: VM
authors: Dixit