| First Author | Kadri Z | Year | 2009 |
| Journal | PLoS Biol | Volume | 7 |
| Issue | 6 | Pages | e1000123 |
| PubMed ID | 19513100 | Mgi Jnum | J:150653 |
| Mgi Id | MGI:3851277 | Doi | 10.1371/journal.pbio.1000123 |
| Citation | Kadri Z, et al. (2009) Direct binding of pRb/E2F-2 to GATA-1 regulates maturation and terminal cell division during erythropoiesis. PLoS Biol 7(6):e1000123 |
| abstractText | 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. |
