Ubiquitin‐specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor
File(s)
Published version
Supporting information
Author(s)
Maertens, GN
El Messaoudi-Aubert, S
Elderkin, S
Hiom, K
Peters, G
Type
Journal Article
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.
Date Issued
2010-07-02
Date Acceptance
2010-05-19
Citation
EMBO Journal, 2010, 29 (15), pp.2553-2565
ISSN
0261-4189
Publisher
EMBO Press
Start Page
2553
End Page
2565
Journal / Book Title
EMBO Journal
Volume
29
Issue
15
Copyright Statement
© 2010 European Molecular Biology Organization. This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial No Derivative Works 3.0 Unported License, which permits distribution and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission.
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
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
Cell Proliferation
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p16
Histones
Humans
Nuclear Proteins
Polycomb Repressive Complex 1
Polycomb-Group Proteins
Protein Binding
Proto-Oncogene Proteins
RNA Interference
Repressor Proteins
Thiolester Hydrolases
Ubiquitin Thiolesterase
Ubiquitination
Developmental Biology
06 Biological Sciences
08 Information And Computing Sciences
11 Medical And Health Sciences
Publication Status
Published