Direct binding of pRb/E2F-2 to GATA-1 regulates maturation and terminal cell division during erythropoiesis
| Autor: | Philippe Leboulch, Masayuki Yamamoto, Osamu Ohneda, Ritsuko Shimizu, Leila Maouche-Chretien, Sylvie Gisselbrecht, Zahra Kadri, Paul-Henri Romeo, Stany Chrétien |
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| Přispěvatelé: | Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université Paris-Saclay, Thérapie génique et contrôle de l'expansion cellulaire (UMR E007), Université Paris-Saclay - Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université Paris-Sud - Paris 11 (UP11), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Department of Molecular and Developmental Biology, University of Tsukuba, Genetics Division, Brigham and Women's Hospital [Boston], This work was supported by ARC and INSERM (SG, P-HR, LM-C, SC), National Institutes of Health grant to PL, the Fondation LeJeune and the Fondation de France (ZK), a Contrat d'Interface International from INSERM (SC), and ERATO-JST and MEXT (RS, OO, MY)., Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Tsukuba = University of Tsukuba, Autard, Delphine |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH : Molecular Sequence Data
Cell division MESH : Transcription Factors Cellular differentiation MESH : NIH 3T3 Cells Amino Acid Motifs Cell Biology/Cell Growth and Division MESH: Amino Acid Sequence Biochemistry Retinoblastoma Protein MESH: Amino Acid Motifs Mice 0302 clinical medicine E2F2 Transcription Factor MESH: E2F2 Transcription Factor MESH : Cell Proliferation MESH: Animals Erythropoiesis GATA1 Transcription Factor Biology (General) Nuclear protein MESH: GATA1 Transcription Factor 0303 health sciences biology General Neuroscience MESH : Amino Acid Sequence Retinoblastoma protein Nuclear Proteins MESH : Protein Binding MESH: Transcription Factors MESH : Cell Division MESH : E2F2 Transcription Factor 3. Good health Cell biology 030220 oncology & carcinogenesis MESH: Cell Division Cell Biology/Nuclear Structure and Function biological phenomena cell phenomena and immunity General Agricultural and Biological Sciences Cell Division Research Article Protein Binding MESH : Amino Acid Motifs QH301-705.5 Cell Biology/Developmental Molecular Mechanisms Molecular Sequence Data General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Erythroid Cells MESH : Erythropoiesis MESH: Cell Proliferation MESH : Mice [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Protein Binding Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Amino Acid Sequence E2F MESH: Mice Molecular Biology Transcription factor MESH : Erythroid Cells Cell Proliferation 030304 developmental biology MESH: Molecular Sequence Data MESH: Humans General Immunology and Microbiology Cell growth MESH: Erythropoiesis MESH : Humans MESH : Nuclear Proteins MESH: Retinoblastoma Protein MESH: Erythroid Cells Molecular biology MESH : GATA1 Transcription Factor NIH 3T3 Cells biology.protein MESH : Animals MESH: Nuclear Proteins MESH : Retinoblastoma Protein MESH: NIH 3T3 Cells Transcription Factors |
| Zdroj: | PLoS Biology PLoS Biology, Public Library of Science, 2009, 7 (6), pp.e1000123. 〈10.1371/journal.pbio.1000123〉 PLoS Biology, Vol 7, Iss 6, p e1000123 (2009) PLoS Biology, Public Library of Science, 2009, 7 (6), pp.e1000123. ⟨10.1371/journal.pbio.1000123⟩ PLoS Biology, 2009, 7 (6), pp.e1000123. ⟨10.1371/journal.pbio.1000123⟩ |
| ISSN: | 1544-9173 1545-7885 |
| DOI: | 10.1371/journal.pbio.1000123〉 |
| Popis: | Cell differentiation is often coupled with cell cycle arrest. Here, we show that direct binding of the erythroid transcription factor GATA-1 to the retinoblastoma protein and the pRb/E2F transcription factor complex is critical for red blood cell formation. 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. Author Summary Red blood cell production, or erythropoiesis, proceeds by a tight coupling of proliferation and differentiation. The earliest erythroid progenitor identifiable possesses remnant stem cell characteristics as it both self-renews and differentiates. Each progenitor gives rise to more than 10,000 cells, including secondary progenitors. Yet, during the next stage of differentiation, much of this renewal capability is lost, and terminal erythroid differentiation progresses in a stepwise manner through several stages separated by a single mitosis. The transcription factor GATA-1 is essential for erythroid differentiation because it induces the expression of all the known erythroid-specific genes. Here, we show that GATA-1 directly interacts with proteins that are central to the process of cell division: the retinoblastoma protein pRb and the transcription factor E2F. Specifically, E2F becomes inactivate after engaging in a GATA-1/pRb/E2F tricomplex. Another erythroid transcription factor, termed FOG-1, is able to displace pRb/E2F from this complex in vitro upon binding to GATA-1. We hypothesize that the liberated pRb/E2F can then be the target of subsequent regulation to ultimately release free E2F, which triggers cell division. The physiological role of this new pathway is evidenced by transgenic mouse experiments with GATA-1 mutants unable to bind pRb/E2F, which result in embryonic lethality by anemia. |
| Databáze: | OpenAIRE |
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