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Direct binding of pRb/E2F-2 to GATA-1 regulates maturation and terminal cell division during erythropoiesis.
oleh: Zahra Kadri, Ritsuko Shimizu, Osamu Ohneda, Leila Maouche-Chretien, Sylvie Gisselbrecht, Masayuki Yamamoto, Paul-Henri Romeo, Philippe Leboulch, Stany Chretien
Format: | Article |
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Diterbitkan: | Public Library of Science (PLoS) 2009-06-01 |
Deskripsi
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.