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. Rodig; Roderick T. Bronson; Stuart H. Orkin; David P. Tuck; Elizaveta V. Benevolenskaya; Matthew Meyerson; William G. Kaelin; Qin Yan

doi:10.1073/pnas.1110104108

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 journal › Article › peer-review

128 Scopus citations

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 language	English (US)
Pages (from-to)	13379-13386
Number of pages	8
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	108
Issue number	33
DOIs	https://doi.org/10.1073/pnas.1110104108
State	Published - Aug 16 2011
Externally published	Yes

Keywords

Chromatin modifier
Histone methyltransferase
Islet cell tumor
Mouse model
Neuroendocrine tumor

ASJC Scopus subject areas

General

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10.1073/pnas.1110104108

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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

Lin, W, Cao, J, Liu, J, Beshiri, ML, Fujiwara, Y, Francis, J, Cherniack, AD, Geisen, C, Blair, LP, Zou, MR, Shen, X, Kawamori, D, Liu, Z, Grisanzio, C, Watanabe, H, Minamishima, YA, Zhang, Q, Kulkarni, RN, Signoretti, S, Rodig, SJ, Bronson, RT, Orkin, SH, Tuck, DP, Benevolenskaya, EV, Meyerson, M, Kaelin, WG & 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, vol. 108, no. 33, pp. 13379-13386. https://doi.org/10.1073/pnas.1110104108

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

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.",

keywords = "Chromatin modifier, Histone methyltransferase, Islet cell tumor, Mouse model, Neuroendocrine tumor",

author = "Wenchu Lin and Jian Cao and Jiayun Liu and Beshiri, {Michael L.} and Yuko Fujiwara and Joshua Francis and Cherniack, {Andrew D.} and Christoph Geisen and Blair, {Lauren P.} and Zou, {Mike R.} and Xiaohua Shen and Dan Kawamori and Zongzhi Liu and Chiara Grisanzio and Hideo Watanabe and Minamishima, {Yoji Andrew} and Qing Zhang and Kulkarni, {Rohit N.} and Sabina Signoretti and Rodig, {Scott J.} and Bronson, {Roderick T.} and Orkin, {Stuart H.} and Tuck, {David P.} and Benevolenskaya, {Elizaveta V.} and Matthew Meyerson and Kaelin, {William G.} and Qin Yan",

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AU - Lin, Wenchu

AU - Cao, Jian

AU - Liu, Jiayun

AU - Beshiri, Michael L.

AU - Fujiwara, Yuko

AU - Francis, Joshua

AU - Cherniack, Andrew D.

AU - Geisen, Christoph

AU - Blair, Lauren P.

AU - Zou, Mike R.

AU - Shen, Xiaohua

AU - Kawamori, Dan

AU - Liu, Zongzhi

AU - Grisanzio, Chiara

AU - Watanabe, Hideo

AU - Minamishima, Yoji Andrew

AU - Zhang, Qing

AU - Kulkarni, Rohit N.

AU - Signoretti, Sabina

AU - Rodig, Scott J.

AU - Bronson, Roderick T.

AU - Orkin, Stuart H.

AU - Tuck, David P.

AU - Benevolenskaya, Elizaveta V.

AU - Meyerson, Matthew

AU - Kaelin, William G.

AU - Yan, Qin

PY - 2011/8/16

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N2 - 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.

AB - 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.

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KW - Histone methyltransferase

KW - Islet cell tumor

KW - Mouse model

KW - Neuroendocrine tumor

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

Abstract

Keywords

ASJC Scopus subject areas

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