Polycomb CBX7 has a unifying role in cellular lifespan

被引:251
|
作者
Gil, J [1 ]
Bernard, D [1 ]
Martínez, D [1 ]
Beach, D [1 ]
机构
[1] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England
基金
英国惠康基金;
关键词
D O I
10.1038/ncb1077
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In contrast to cancer cells and embryonic stem cells, the lifespan of primary human cells is finite. After a defined number of population doublings, cells enter in an irreversible growth-arrested state termed replicative senescence(1). Mutations of genes involved in immortalization can contribute to cancer(2,3). In a genetic screen for cDNAs bypassing replicative senescence of normal human prostate epithelial cells (HPrEC), we identified CBX7, a gene that encodes a Polycomb protein, as shown by sequence homology, its interaction with Ring1 and its localization to nuclear Polycomb bodies. CBX7 extends the lifespan of a wide range of normal human cells and immortalizes mouse fibroblasts by downregulating expression of the Ink4a/Arf locus. CBX7 does not inter-function or colocalize with Bmi1, and both can exert their actions independently of each other as shown by reverse genetics. CBX7 expression is downregulated during replicative senescence and its ablation by short-hairpin RNA (shRNA) treatment inhibited growth of normal cells though induction of the Ink4a/Arf locus. Taken together, these data show that CBX7 controls cellular lifespan through regulation of both the p16(Ink4a)/Rb and the Arf/p53 pathways.
引用
收藏
页码:67 / U19
页数:10
相关论文
共 50 条
  • [1] Polycomb CBX7 has a unifying role in cellular lifespan
    Jesús Gil
    David Bernard
    Dolores Martínez
    David Beach
    Nature Cell Biology, 2004, 6 : 67 - 72
  • [2] Author Correction: Polycomb CBX7 has a unifying role in cellular lifespan
    Jesús Gil
    David Bernard
    Dolores Martínez
    David Beach
    Nature Cell Biology, 2022, 24 : 1445 - 1445
  • [3] Polycomb CBX7 has a unifying role in cellular lifespan (vol 6, pg 67, 2004)
    Gil, Jesus
    Bernard, David
    Martinez, Dolores
    Beach, David
    NATURE CELL BIOLOGY, 2022, 24 (09) : 1445 - 1445
  • [4] Polycomb protein family member CBX7 plays a critical role in cancer progression
    Pallante, Pierlorenzo
    Forzati, Floriana
    Federico, Antonella
    Arra, Claudio
    Fusco, Alfredo
    AMERICAN JOURNAL OF CANCER RESEARCH, 2015, 5 (05): : 1594 - 1601
  • [5] Role of the chromobox protein CBX7 in lymphomagenesis
    Scott, Clare L.
    Gil, Jesus
    Hernando, Eva
    Teruya-Feldstein, Julie
    Narita, Masako
    Martinez, Dolores
    Visakorpi, Tapio
    Mu, David
    Cordon-Cardo, Carlos
    Peters, Gordon
    Beach, David
    Lowe, Scott W.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (13) : 5389 - 5394
  • [6] Discovery and Characterization of a Cellular Potent Positive Allosteric Modulator of the Polycomb Repressive Complex 1 Chromodomain, CBX7
    Lamb, Kelsey N.
    Bsteh, Daniel
    Dishman, Sarah N.
    Moussa, Hagar F.
    Fan, Huitao
    Stuckey, Jacob I.
    Norris, Jacqueline L.
    Cholensky, Stephanie H.
    Li, Dongxu
    Wang, Jingkui
    Sagum, Cari
    Stanton, Benjamin Z.
    Bedford, Mark T.
    Pearce, Kenneth H.
    Kenakin, Terry P.
    Kireev, Dmitri B.
    Wang, Gang Greg
    James, Lindsey I.
    Bell, Oliver
    Frye, Stephen V.
    CELL CHEMICAL BIOLOGY, 2019, 26 (10): : 1365 - +
  • [7] OVEREXPRESSION OF POLYCOMB GENE CBX7 IN HEMATOPOIETIC CELLS INDUCES DISTINCT TYPES OF LEUKEMIA
    Klauke, K.
    Broekhuis, M. J. C.
    Olthof, S. G. M.
    Ritsema, M.
    Dykstra, B. D.
    Bystrykh, L. V.
    de Haan, G.
    EXPERIMENTAL HEMATOLOGY, 2010, 38 (09) : S37 - S38
  • [8] OPPOSING EFFECTS ON HSC SELF-RENEWAL INDUCED BY OVEREXPRESSION OF THE POLYCOMB GENES CBX7 AND CBX8
    Klauke, K.
    Olthof, S. G. M.
    Weersing, E.
    Kalmykowa, O.
    Gerrits, A.
    Dykstra, B. J.
    Bystrykh, L. V.
    de Haan, G.
    EXPERIMENTAL HEMATOLOGY, 2009, 37 (09) : S15 - S15
  • [9] MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation
    O'Loghlen, Ana
    Munoz-Cabello, Ana M.
    Gaspar-Maia, Alexandre
    Wu, Hsan-Au
    Banito, Ana
    Kunowska, Natalia
    Racek, Tomas
    Pemberton, Helen N.
    Beolchi, Patrizia
    Lavial, Fabrice
    Masui, Osamu
    Vermeulen, Michiel
    Carroll, Thomas
    Graumann, Johannes
    Heard, Edith
    Dillon, Niall
    Azuara, Veronique
    Snijders, Ambrosius P.
    Peters, Gordon
    Bernstein, Emily
    Gil, Jesus
    CELL STEM CELL, 2012, 10 (01) : 33 - 46
  • [10] Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration
    Duan, Run-Shan
    Tang, Gang-Bin
    Du, Hong-Zhen
    Hu, Yi-Wen
    Liu, Pei-Pei
    Xu, Ya-Jie
    Zeng, Yu-Qiang
    Zhang, Shuang-Feng
    Wang, Rui-Ying
    Teng, Zhao-Qian
    Liu, Chang-Mei
    CELL DEATH AND DIFFERENTIATION, 2018, 25 (09): : 1598 - 1611