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.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Kadri Z,Shimizu R,Ohneda O,Maouche-Chretien L,Gisselbrecht S,Yamamoto M,Romeo PH,Leboulch P,Chretien S

doi

10.1371/journal.pbio.1000123

subject

Has Abstract

pub_date

2009-06-09 00:00:00

pages

e1000123

issue

6

eissn

1544-9173

issn

1545-7885

journal_volume

7

pub_type

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