Direct Binding of pRb/E2F-2 to GATA-1 Regulates Maturation and Terminal Cell Division during Erythropoiesis

被引:63
作者
Kadri, Zahra [1 ,2 ,3 ,4 ]
Shimizu, Ritsuko [5 ]
Ohneda, Osamu [5 ]
Maouche-Chretien, Leila [1 ,2 ,3 ,4 ]
Gisselbrecht, Sylvie [3 ,4 ]
Yamamoto, Masayuki [5 ]
Romeo, Paul-Henri [3 ,4 ]
Leboulch, Philippe [1 ,2 ,6 ,7 ]
Chretien, Stany [1 ,2 ,3 ,4 ,6 ,7 ]
机构
[1] CEA, Inst Emerging Dis & Innovat Therapies, Fontenay Aux Roses, France
[2] Univ Paris 11, UMR INSERM U962, CEA, Fontenay Aux Roses, France
[3] Inst Cochin Genet Mol, Dept Hematol, INSERM U567, CNRS UMR 8104, F-75014 Paris, France
[4] Univ Paris 05, Paris, France
[5] Univ Tsukuba, Dept Mol & Dev Biol, Ctr TARA, ERATO Environm Response Project, Tsukuba, Ibaraki, Japan
[6] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Boston, MA USA
基金
美国国家卫生研究院;
关键词
TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; ERYTHROID-DIFFERENTIATION; GENE-EXPRESSION; DEFINITIVE ERYTHROPOIESIS; RETINOBLASTOMA PROTEIN; INHERITED MUTATION; TUMOR-SUPPRESSOR; IN-VIVO; RB;
D O I
10.1371/journal.pbio.1000123
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
How cell proliferation subsides as cells terminally differentiate remains largely enigmatic, although this phenomenon is central to the existence of multicellular organisms. Here, we show that GATA-1, the master transcription factor of erythropoiesis, forms a tricomplex with the retinoblastoma protein (pRb) and E2F-2. This interaction requires a LXCXE motif that is evolutionary conserved among GATA-1 orthologs yet absent from the other GATA family members. GATA-1/pRb/E2F-2 complex formation stalls cell proliferation and steers erythroid precursors towards terminal differentiation. This process can be disrupted in vitro by FOG-1, which displaces pRb/E2F-2 from GATA-1. A GATA-1 mutant unable to bind pRb fails to inhibit cell proliferation and results in mouse embryonic lethality by anemia. These findings clarify the previously suspected cell-autonomous role of pRb during erythropoiesis and may provide a unifying molecular mechanism for several mouse phenotypes and human diseases associated with GATA-1 mutations.
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页数:15
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共 47 条
  • [1] Coregulation of GATA factors by the Friend of GATA (FOG) family of multitype zinc finger proteins
    Cantor, AB
    Orkin, SH
    [J]. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2005, 16 (01) : 117 - 128
  • [2] GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis
    Chang, AN
    Cantor, AB
    Fujiwara, Y
    Lodish, MB
    Droho, S
    Crispino, JD
    Orkin, SH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (14) : 9237 - 9242
  • [3] ALTERNATIVE TRANSCRIPTION AND SPLICING OF THE HUMAN PORPHOBILINOGEN DEAMINASE GENE RESULT EITHER IN TISSUE-SPECIFIC OR IN HOUSEKEEPING EXPRESSION
    CHRETIEN, S
    DUBART, A
    BEAUPAIN, D
    RAICH, N
    GRANDCHAMP, B
    ROSA, J
    GOOSSENS, M
    ROMEO, PH
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (01) : 6 - 10
  • [4] Cell-intrinsic requirement for pRb in erythropoiesis
    Clark, AJ
    Doyle, KM
    Humbert, PO
    [J]. BLOOD, 2004, 104 (05) : 1324 - 1326
  • [5] REQUIREMENT FOR A FUNCTIONAL RB-1 GENE IN MURINE DEVELOPMENT
    CLARKE, AR
    MAANDAG, ER
    VANROON, M
    VANDERLUGT, NMT
    VANDERVALK, M
    HOOPER, ML
    BERNS, A
    RIELE, HT
    [J]. NATURE, 1992, 359 (6393) : 328 - 330
  • [6] GATA1 in normal and malignant hematopoiesis
    Crispino, JD
    [J]. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2005, 16 (01) : 137 - 147
  • [7] Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation:: The GATA-1:FOG complex
    Crispino, JD
    Lodish, MB
    MacKay, JP
    Orkin, SH
    [J]. MOLECULAR CELL, 1999, 3 (02) : 219 - 228
  • [8] Deregulated E2f-2 underlies cell cycle and maturation defects in retinoblastoma null erythroblasts
    Dirlam, Alexandra
    Spike, Benjamin T.
    Macleod, Kay F.
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (24) : 8713 - 8728
  • [9] A GATA-1-regulated microRNA locus essential for erythropoiesis
    Dore, Louis C.
    Amigo, Julio D.
    dos Santos, Camila O.
    Zhang, Zhe
    Gai, Xiaowu
    Tobias, John W.
    Yu, Duonan
    Klein, Alyssa M.
    Dorman, Christine
    Wu, Weisheng
    Hardison, Ross C.
    Paw, Barry H.
    Weiss, Mitchell J.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (09) : 3333 - 3338
  • [10] Constitutive expression of GATA-1 interferes with the cell-cycle regulation
    Dubart, A
    Romeo, PH
    Vainchenker, W
    Dumenil, D
    [J]. BLOOD, 1996, 87 (09) : 3711 - 3721