Format

Send to

Choose Destination
Mol Cell. 2016 May 19;62(4):558-71. doi: 10.1016/j.molcel.2016.03.030. Epub 2016 Apr 28.

ATXN7L3 and ENY2 Coordinate Activity of Multiple H2B Deubiquitinases Important for Cellular Proliferation and Tumor Growth.

Author information

1
Department of Epigenetics & Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA; Center for Cancer Epigenetics, Houston, TX 77030, USA. Electronic address: batanass@mdanderson.org.
2
University of Missouri - Kansas City, Kansas City, MO 64110, USA.
3
Department of Epigenetics & Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA; Center for Cancer Epigenetics, Houston, TX 77030, USA; Program in Epigenetics and Molecular Carcinogenesis, Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA.
4
Department of Epigenetics & Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA; Center for Cancer Epigenetics, Houston, TX 77030, USA.
5
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
6
University of Arkansas for Medical Sciences, Biochemistry and Molecular Biology, Little Rock, AR 72205, USA.
7
Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
8
Department of Epigenetics & Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA; Center for Cancer Epigenetics, Houston, TX 77030, USA; Program in Epigenetics and Molecular Carcinogenesis, Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA. Electronic address: sroth@mdanderson.org.

Abstract

Histone H2B monoubiquitination (H2Bub1) is centrally involved in gene regulation. The deubiquitination module (DUBm) of the SAGA complex is a major regulator of global H2Bub1 levels, and components of this DUBm are linked to both neurodegenerative diseases and cancer. Unexpectedly, we find that ablation of USP22, the enzymatic center of the DUBm, leads to a reduction, rather than an increase, in global H2bub1 levels. In contrast, depletion of non-enzymatic components, ATXN7L3 or ENY2, results in increased H2Bub1. These observations led us to discover two H2Bub1 DUBs, USP27X and USP51, which function independently of SAGA and compete with USP22 for ATXN7L3 and ENY2 for activity. Like USP22, USP51 and USP27X are required for normal cell proliferation, and their depletion suppresses tumor growth. Our results reveal that ATXN7L3 and ENY2 orchestrate activities of multiple deubiquitinating enzymes and that imbalances in these activities likely potentiate human diseases including cancer.

PMID:
27132940
PMCID:
PMC4874879
DOI:
10.1016/j.molcel.2016.03.030
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center