Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1

被引：123

作者：

Lin, Wenchu ^{[1
]}

Cao, Jian ^{[2
]}

Liu, Jiayun ^{[1
]}

Beshiri, Michael L. ^{[3
]}

Fujiwara, Yuko ^{[4
,5
]}

Francis, Joshua ^{[1
]}

Cherniack, Andrew D. ^{[1
]}

Geisen, Christoph ^{[1
,7
]}

Blair, Lauren P. ^{[2
]}

Zou, Mike R. ^{[2
]}

Shen, Xiaohua ^{[4
,5
]}

Kawamori, Dan ^{[8
]}

Liu, Zongzhi ^{[2
]}

Grisanzio, Chiara ^{[1
,9
]}

Watanabe, Hideo ^{[1
]}

Minamishima, Yoji Andrew ^{[1
]}

Zhang, Qing ^{[1
]}

Kulkarni, Rohit N. ^{[8
]}

Signoretti, Sabina ^{[1
,9
]}

Rodig, Scott J. ^{[9
]}

Bronson, Roderick T. ^{[10
]}

Orkin, Stuart H. ^{[4
,5
,7
,11
]}

Tuck, David P. ^{[2
]}

Benevolenskaya, Elizaveta V. ^{[3
]}

Meyerson, Matthew ^{[1
,6
,12
]}

Kaelin, William G., Jr. ^{[1
,7
]}

Yan, Qin ^{[2
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA

[3] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA

[4] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA

[6] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA

[7] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[8] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Med,Dept Med, Boston, MA 02115 USA

[9] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[11] Harvard Stem Cell Inst, Boston, MA 02115 USA

[12] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 33期

基金：

美国国家卫生研究院;

关键词：

mouse model; histone methyltransferase; chromatin modifier; neuroendocrine tumor; islet cell tumor; MULTIPLE ENDOCRINE NEOPLASIA; METHYLTRANSFERASE COMPLEX; REPRESSES TRANSCRIPTION; MOUSE MODEL; GENE; METHYLATION; CANCER; INACTIVATION; DEACETYLASE; EXPRESSION;

D O I：

10.1073/pnas.1110104108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Aberrations in epigenetic processes, such as histone methylation, can cause cancer. Retinoblastoma binding protein 2 (RBP2; also called JARID1A or KDM5A) can demethylate tri- and dimethylated lysine 4 in histone H3, which are epigenetic marks for transcriptionally active chromatin, whereas the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor promotes H3K4 methylation. Previous studies suggested that inhibition of RBP2 contributed to tumor suppression by the retinoblastoma protein (pRB). Here, we show that genetic ablation of Rbp2 decreases tumor formation and prolongs survival in Rb1(+/-) mice and Men1-defective mice. These studies link RBP2 histone demethylase activity to tumorigenesis and nominate RBP2 as a potential target for cancer therapy.

引用

页码：13379 / 13386

页数：8

共 71 条

[1] Binding of pRB to the PHD protein RBP2 promotes cellular differentiation [J].

Benevolenskaya, EV ;

Murray, HL ;

Branton, P ;

Young, RA ;

Kaelin, WG .

MOLECULAR CELL, 2005, 18 (06) :623-635

[2] A bivalent chromatin structure marks key developmental genes in embryonic stem cells [J].

Bernstein, BE ;

Mikkelsen, TS ;

Xie, XH ;

Kamal, M ;

Huebert, DJ ;

Cuff, J ;

Fry, B ;

Meissner, A ;

Wernig, M ;

Plath, K ;

Jaenisch, R ;

Wagschal, A ;

Feil, R ;

Schreiber, SL ;

Lander, ES .

CELL, 2006, 125 (02) :315-326

[3]

Blair Lauren P, 2011, Cancers (Basel), V3, P1383, DOI 10.3390/cancers3011383

[4] Retinoblastoma protein recruits histone deacetylase to repress transcription [J].

Brehm, A ;

Miska, EA ;

McCance, DJ ;

Reid, JL ;

Bannister, AJ ;

Kouzarides, T .

NATURE, 1998, 391 (6667) :597-601

[5] Positional cloning of the gene for multiple endocrine neoplasia-type 1 [J].

Chandrasekharappa, SC ;

Guru, SC ;

Manickam, P ;

Olufemi, SE ;

Collins, FS ;

EmmertBuck, MR ;

Debelenko, LV ;

Zhuang, ZP ;

Lubensky, IA ;

Liotta, LA ;

Crabtree, JS ;

Wang, YP ;

Roe, BA ;

Weisemann, J ;

Boguski, MS ;

Agarwal, SK ;

Kester, MB ;

Kim, YS ;

Heppner, C ;

Dong, QH ;

Spiegel, AM ;

Burns, AL ;

Marx, SJ .

SCIENCE, 1997, 276 (5311) :404-407

[6] RBP2 belongs to a family of demethylases, specific for tri- and dimethylated lysine 4 on histone 3 [J].

Christensen, Jesper ;

Agger, Karl ;

Cloos, Paul A. C. ;

Pasini, Diego ;

Rose, Simon ;

Sennels, Lau ;

Rappsilber, Juri ;

Hansen, Klaus H. ;

Salcini, Anna Elisabetta ;

Helin, Kristian .

CELL, 2007, 128 (06) :1063-1076

[7] REQUIREMENT FOR A FUNCTIONAL RB-1 GENE IN MURINE DEVELOPMENT [J].

CLARKE, AR ;

MAANDAG, ER ;

VANROON, M ;

VANDERLUGT, NMT ;

VANDERVALK, M ;

HOOPER, ML ;

BERNS, A ;

RIELE, HT .

NATURE, 1992, 359 (6393) :328-330

[8] JmjC:: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2β [J].

Clissold, PM ;

Ponting, CP .

TRENDS IN BIOCHEMICAL SCIENCES, 2001, 26 (01) :7-9

[9] Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease [J].

Cloos, Paul A. C. ;

Christensen, Jesper ;

Agger, Karl ;

Helin, Kristian .

GENES & DEVELOPMENT, 2008, 22 (09) :1115-1140

[10] Of mice and MEN1: Insulinomas in a conditional mouse knockout [J].

Crabtree, JS ;

Scacheri, PC ;

Ward, JM ;

McNally, SR ;

Swain, GP ;

Montagna, C ;

Hager, JH ;

Hanahan, D ;

Edlund, H ;

Magnuson, MA ;

Garrett-Beal, L ;

Burns, AL ;

Ried, T ;

Chandrasekharappa, SC ;

Marx, SJ ;

Spiegel, AM ;

Collins, FS .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (17) :6075-6085

← 1 2 3 4 5 6 7 8 →