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

被引：110

作者：

Atanassov, Boyko S. ^{[1
,2
]}

Mohan, Ryan D. ^{[3
]}

Lan, Xianjiang ^{[1
,2
,5
]}

Kuang, Xianghong ^{[1
,2
]}

Lu, Yue ^{[1
,2
]}

Lin, Kevin ^{[1
,2
]}

McIvor, Elizabeth ^{[1
,2
]}

Li, Wenqian ^{[1
,2
,5
]}

Zhang, Ying ^{[4
]}

Florens, Laurence ^{[4
]}

Byrum, Stephanie D. ^{[6
]}

Mackintosh, Samuel G. ^{[6
]}

Calhoun-Davis, Tammy ^{[1
,2
]}

Koutelou, Evangelia ^{[1
,2
]}

Wang, Li ^{[1
,2
]}

Tang, Dean G. ^{[1
,2
]}

Tackett, Alan J.

Washburn, Michael P. ^{[4
,7
]}

Workman, Jerry L. ^{[4
]}

Dent, Sharon Y. R. ^{[1
,2
,5
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX 78957 USA

[2] Ctr Canc Epigenet, Houston, TX 77030 USA

[3] Univ Missouri, Kansas City, MO 64110 USA

[4] Stowers Inst Med Res, Kansas City, MO 64110 USA

[5] Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Program Epigenet & Mol Carcinogenesis, Smithville, TX 78957 USA

[6] Univ Arkansas Med Sci, Biochem & Mol Biol, Little Rock, AR 72205 USA

[7] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA

来源：

MOLECULAR CELL | 2016年 / 62卷 / 04期

关键词：

HISTONE H2B; TRANSCRIPTIONAL ACTIVATION; STRUCTURAL BASIS; POOR-PROGNOSIS; SAGA; COMPLEX; CANCER; USP22; SUBUNIT; UBIQUITINATION;

D O I：

10.1016/j.molcel.2016.03.030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 nonenzymatic 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.

引用

页码：558 / 571

页数：14

共 42 条

[1] USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1 [J].

Atanassov, Boyko S. ;

Dent, Sharon Y. R. .

EMBO REPORTS, 2011, 12 (09) :924-930

[2] The SAGA coactivator complex acts on the whole transcribed genome and is required for RNA polymerase II transcription [J].

Bonnet, Jacques ;

Wang, Chen-Yi ;

Baptista, Tiago ;

Vincent, Stephane D. ;

Hsiao, Wei-Chun ;

Stierle, Matthieu ;

Kao, Cheng-Fu ;

Tora, Laszlo ;

Devys, Didier .

GENES & DEVELOPMENT, 2014, 28 (18) :1999-2012

[3]

Byrum S, 2012, METHODS MOL BIOL, V833, P143, DOI 10.1007/978-1-61779-477-3_10

[4] Steroid hormone receptor coactivation and alternative RNA splicing by U2AF65-Related proteins CAPERα and CAPERβ [J].

Dowhan, DH ;

Hong, EP ;

Auboeuf, D ;

Dennis, AP ;

Wilson, MM ;

Berget, SM ;

O'Malley, BW .

MOLECULAR CELL, 2005, 17 (03) :429-439

[5] Pfam: the protein families database [J].

Finn, Robert D. ;

Bateman, Alex ;

Clements, Jody ;

Coggill, Penelope ;

Eberhardt, Ruth Y. ;

Eddy, Sean R. ;

Heger, Andreas ;

Hetherington, Kirstie ;

Holm, Liisa ;

Mistry, Jaina ;

Sonnhammer, Erik L. L. ;

Tate, John ;

Punta, Marco .

NUCLEIC ACIDS RESEARCH, 2014, 42 (D1) :D222-D230

[6] KAP-1, a novel corepressor for the highly conserved KRAB repression domain [J].

Friedman, JR ;

Fredericks, WJ ;

Jensen, DE ;

Speicher, DW ;

Huang, XP ;

Neilson, EG ;

Rauscher, FJ .

GENES & DEVELOPMENT, 1996, 10 (16) :2067-2078

[7] Cotranscriptional histone H2B monoubiquitylation is tightly coupled with RNA polymerase II elongation rate [J].

Fuchs, Gilad ;

Hollander, Dror ;

Voichek, Yoav ;

Ast, Gil ;

Oren, Moshe .

GENOME RESEARCH, 2014, 24 (10) :1572-1583

[8] Genomic models of metastatic cancer - Functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated polycomb group (PcG) protein chromatin silencing pathway [J].

Glinsky, GV .

CELL CYCLE, 2006, 5 (11) :1208-1216

[9] Ubiquitin-specific peptidase 22 overexpression may promote cancer progression and poor prognosis in human gastric carcinoma [J].

He, Yan ;

Jin, Yin-Ji ;

Zhang, Yu-Hua ;

Meng, Hong-Xue ;

Zhao, Bao-Shan ;

Jiang, Yang ;

Zhu, Ji-Wei ;

Liang, Guan-Ying ;

Kong, Dan ;

Jin, Xiao-Ming .

TRANSLATIONAL RESEARCH, 2015, 165 (03) :407-416

[10] A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances [J].

Hein, Marco Y. ;

Hubner, Nina C. ;

Poser, Ina ;

Cox, Juergen ;

Nagaraj, Nagarjuna ;

Toyoda, Yusuke ;

Gak, Igor A. ;

Weisswange, Ina ;

Mansfeld, Joerg ;

Buchholz, Frank ;

Hyman, Anthony A. ;

Mann, Matthias .

CELL, 2015, 163 (03) :712-723

← 1 2 3 4 5 →