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

Goedele N. Maertens; Selma El Messaoudi-Aubert; Sarah Elderkin; Kevin Hiom; Gordon Peters

doi:10.1038/emboj.2010.129

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 journal › Article › peer-review

143 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 language	English
Pages (from-to)	2553-2565
Number of pages	13
Journal	EMBO Journal
Volume	29
Issue number	15
DOIs	https://doi.org/10.1038/emboj.2010.129
Publication status	Published - 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

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title = "Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor",

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",

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",

author = "Maertens, \{Goedele N.\} and \{El Messaoudi-Aubert\}, Selma and Sarah Elderkin and Kevin Hiom and Gordon Peters",

year = "2010",

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doi = "10.1038/emboj.2010.129",

language = "English",

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T1 - Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor

AU - Maertens, Goedele N.

AU - El Messaoudi-Aubert, Selma

AU - Elderkin, Sarah

AU - Hiom, Kevin

AU - Peters, Gordon

PY - 2010/8/4

Y1 - 2010/8/4

N2 - 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

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

KW - chromatin

KW - INK4a

KW - Polycomb

KW - transcription

KW - ubiquitination

KW - HISTONE H2A UBIQUITINATION

KW - HUMAN-DIPLOID FIBROBLASTS

KW - DEUBIQUITINATING ENZYME

KW - GROUP PROTEINS

KW - REPLICATIVE SENESCENCE

KW - CELLULAR SENESCENCE

KW - P53 STABILIZATION

KW - DNA-DAMAGE

KW - STEM-CELLS

KW - LIFE-SPAN

UR - https://www.scopus.com/pages/publications/77955419051

U2 - 10.1038/emboj.2010.129

DO - 10.1038/emboj.2010.129

M3 - Article

C2 - 20601937

SN - 0261-4189

VL - 29

SP - 2553

EP - 2565

JO - EMBO Journal

JF - EMBO Journal

IS - 15

ER -

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

Abstract

Keywords

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