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EMBO J. 2010 Aug 4;29(15):2553-65. doi: 10.1038/emboj.2010.129. Epub 2010 Jul 2.

Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor.

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  • 1Cancer Research UK, London Research Institute, London, UK.

Abstract

An important facet of transcriptional repression by Polycomb repressive complex 1 (PRC1) is the mono-ubiquitination of histone H2A by the combined action of the Posterior sex combs (Psc) and Sex combs extra (Sce) proteins. Here, we report that two ubiquitin-specific proteases, USP7 and USP11, co-purify with human PRC1-type complexes through direct interactions with the Psc orthologues MEL18 and BMI1, and with other PRC1 components. Ablation of either USP7 or USP11 in primary human fibroblasts results in de-repression of the INK4a tumour suppressor accompanied by loss of PRC1 binding at the locus and a senescence-like proliferative arrest. Mechanistically, USP7 and USP11 regulate the ubiquitination status of the Psc and Sce proteins themselves, thereby affecting their turnover and abundance. Our results point to a novel function for USPs in the regulation and function of Polycomb complexes.

PMID:
20601937
[PubMed - indexed for MEDLINE]
PMCID:
PMC2928679
Free PMC Article
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