| First Author | Maertens GN | Year | 2010 |
| Journal | EMBO J | Volume | 29 |
| Issue | 15 | Pages | 2553-65 |
| PubMed ID | 20601937 | Mgi Jnum | J:163381 |
| Mgi Id | MGI:4821877 | Doi | 10.1038/emboj.2010.129 |
| Citation | Maertens GN, et al. (2010) Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor. EMBO J 29(15):2553-65 |
| abstractText | 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. |
