Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lackingRb1orMen1

• DOI: 10.1073/pnas.1110104108
• Publication Date: 2011-07-26T04:02:29Z
• Authors: Wenchu Lin; Jian Cao; Jiayun Liu; Michael L. Beshiri; Yuko Fujiwara; Joshua Francis; Andrew D. Cherniack; Christoph Geisen; Lauren P. Blair; Mike R. Zou; Xiaohua Shen; Dan Kawamori; Zongzhi Liu; Chiara Grisanzio; Hideo Watanabe; Yoji Andrew Minam...; Qing Zhang; Rohit N. Kulkarni; Sabina Signoretti; Scott J. Rodig; Roderick T. Bronson; Stuart H. Orkin; David P. Tuck; Elizaveta V. Bene...; Matthew Meyerson; William G. Kaelin; Qin Yan
• Keywords: Demethylase; MEN1; Retinoblastoma; Retinoblastoma protein

Aberrations in epigenetic processes, such as histone methylation, can cause cancer. Retinoblastoma binding protein 2 (RBP2; also called JARID1A or KDM5A) demethylate tri- and dimethylated lysine 4 H3, which are 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 suppression by retinoblastoma (pRB). Here, we show genetic ablation Rbp2 decreases formation prolongs survival Rb1(+/-) mice Men1-defective mice. These link demethylase activity tumorigenesis nominate a potential target cancer therapy.