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

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 Minamishima, Qing Zhang, Rohit N. Kulkarni, Sabina Signoretti, Scott J. RodigRoderick T. Bronson, Stuart H. Orkin, David P. Tuck, Elizaveta V. Benevolenskaya, Matthew Meyerson, William G. Kaelin, Qin Yan

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)13379-13386
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number33
DOIs
Publication statusPublished - 2011 Aug 16

Keywords

  • Chromatin modifier
  • Histone methyltransferase
  • Islet cell tumor
  • Mouse model
  • Neuroendocrine tumor

ASJC Scopus subject areas

  • General

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    Lin, W., Cao, J., Liu, J., Beshiri, M. L., Fujiwara, Y., Francis, J., Cherniack, A. D., Geisen, C., Blair, L. P., Zou, M. R., Shen, X., Kawamori, D., Liu, Z., Grisanzio, C., Watanabe, H., Minamishima, Y. A., Zhang, Q., Kulkarni, R. N., Signoretti, S., ... Yan, Q. (2011). Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proceedings of the National Academy of Sciences of the United States of America, 108(33), 13379-13386. https://doi.org/10.1073/pnas.1110104108