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

Goedele N Maertens ^[1] ; Selma El Messaoudi-Aubert ^[1] ; Sarah Elderkin ^[2] ; Kevin Hiom ^[3] ; Gordon Peters ^[1]
1. [1] London Research Institute
  
  London Research Institute
  
  Reino Unido
2. [2] Babraham Institute
  
  Babraham Institute
  
  Cambridge District, Reino Unido
3. [3] University of Dundee
  
  University of Dundee
  
  Reino Unido
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Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 29, Nº. 15, 2010, págs. 2553-2565
Idioma: inglés
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Resumen
- 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.