TY - JOUR
T1 - Direct binding of pRb/E2F-2 to GATA-1 regulates maturation and terminal cell division during erythropoiesis
AU - Kadri, Zahra
AU - Shimizu, Ritsuko
AU - Ohneda, Osamu
AU - Maouche-Chretien, Leila
AU - Gisselbrecht, Sylvie
AU - Yamamoto, Masayuki
AU - Romeo, Paul Henri
AU - Leboulch, Philippe
AU - Chretien, Stany
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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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U2 - 10.1371/journal.pbio.1000123
DO - 10.1371/journal.pbio.1000123
M3 - Article
C2 - 19513100
AN - SCOPUS:67649981723
SN - 1544-9173
VL - 7
JO - PLoS Biology
JF - PLoS Biology
IS - 6
M1 - e1000123
ER -
