USP37
Developmental stage
Induced in G1 phase, accumulates at G1/S transition, and degraded in late mitosis following ubiquitination and degradation by the APC(CDH1) complex.
Domain
The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination.
Function
Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response (PubMed:26299517, PubMed:27296872, PubMed:31911859, PubMed:34509474). Antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2) (PubMed:21596315). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1 (PubMed:27296872). Plays also an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability (PubMed:34509474). Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM (PubMed:34606619). Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM (PubMed:34606619). Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI (PubMed:31911859). Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination (PubMed:26299517).
Post-translational modifications
Polyubiquitinated via 'Lys-11'-linked ubiquitin by the APC(CDH1) complex during late mitosis, leading to its degradation. Able to mediate auto-deubiquitination.
Phosphorylated at Ser-628 by CDK2 during G1/S phase but not during mitosis; phosphorylation at Ser-628 is required for deubiquitinase activity. Also polyubiquitinated during early G1 phase, without leading to degradation (PubMed:21596315). Phosphorylated at Ser-114 by ATM following DNA damage, which in turn increases its deubiquitination activity towards BLM (PubMed:34606619).
Sequence Similarities
Belongs to the peptidase C19 family.
Tissue Specificity
Expressed in brain and prostate.
Cellular localization
- Nucleus
- Chromosome
Alternative names
KIAA1594, USP37, Ubiquitin carboxyl-terminal hydrolase 37, Deubiquitinating enzyme 37, Ubiquitin thioesterase 37, Ubiquitin-specific-processing protease 37