title: Direct binding of pRb/E2F-2 to GATA-1 regulates maturation and terminal cell division during erythropoiesis.
abstract: 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.
authors.affiliation: CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kadri
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Shimizu
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohneda
authors.forename: Leila
authors.initials: L
authors.lastname: Maouche-Chretien
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gisselbrecht
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Romeo
authors.forename: Philippe
authors.initials: P
authors.lastname: Leboulch
authors.forename: Stany
authors.initials: S
authors.lastname: Chretien
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division; D049109:Cell Proliferation; D050703:E2F2 Transcription Factor / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis; D050982:GATA1 Transcription Factor / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050703:E2F2 Transcription Factor; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C498432:ZFPM1 protein, human