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

Goedele N. Maertens (Lead / Corresponding author), Selma El Messaoudi-Aubert, Sarah Elderkin, Kevin Hiom, Gordon Peters (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    91 Citations (Scopus)

    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. The EMBO Journal (2010) 29, 2553-2565. doi:10.1038/emboj.2010.129; Published online 2 July 2010

    Original languageEnglish
    Pages (from-to)2553-2565
    Number of pages13
    JournalEMBO Journal
    Volume29
    Issue number15
    DOIs
    Publication statusPublished - 4 Aug 2010

    Keywords

    • chromatin
    • INK4a
    • Polycomb
    • transcription
    • ubiquitination
    • HISTONE H2A UBIQUITINATION
    • HUMAN-DIPLOID FIBROBLASTS
    • DEUBIQUITINATING ENZYME
    • GROUP PROTEINS
    • REPLICATIVE SENESCENCE
    • CELLULAR SENESCENCE
    • P53 STABILIZATION
    • DNA-DAMAGE
    • STEM-CELLS
    • LIFE-SPAN

    Cite this

    Maertens, Goedele N. ; El Messaoudi-Aubert, Selma ; Elderkin, Sarah ; Hiom, Kevin ; Peters, Gordon. / Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor. In: EMBO Journal. 2010 ; Vol. 29, No. 15. pp. 2553-2565.
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    Maertens, GN, El Messaoudi-Aubert, S, Elderkin, S, Hiom, K & Peters, G 2010, 'Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor', EMBO Journal, vol. 29, no. 15, pp. 2553-2565. https://doi.org/10.1038/emboj.2010.129

    Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor. / Maertens, Goedele N. (Lead / Corresponding author); El Messaoudi-Aubert, Selma; Elderkin, Sarah; Hiom, Kevin; Peters, Gordon (Lead / Corresponding author).

    In: EMBO Journal, Vol. 29, No. 15, 04.08.2010, p. 2553-2565.

    Research output: Contribution to journalArticle

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    AU - Maertens, Goedele N.

    AU - El Messaoudi-Aubert, Selma

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    AU - Hiom, Kevin

    AU - Peters, Gordon

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    AB - 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. The EMBO Journal (2010) 29, 2553-2565. doi:10.1038/emboj.2010.129; Published online 2 July 2010

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    KW - DEUBIQUITINATING ENZYME

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    KW - REPLICATIVE SENESCENCE

    KW - CELLULAR SENESCENCE

    KW - P53 STABILIZATION

    KW - DNA-DAMAGE

    KW - STEM-CELLS

    KW - LIFE-SPAN

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