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.
Type de document :
Article dans une revue
PLoS Biology, Public Library of Science, 2009, 7 (6), pp.e1000123. 〈10.1371/journal.pbio.1000123〉
Liste complète des métadonnées

Littérature citée [46 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00707647
Contributeur : Delphine Autard <>
Soumis le : mercredi 13 juin 2012 - 11:22:18
Dernière modification le : jeudi 1 février 2018 - 01:32:43
Document(s) archivé(s) le : vendredi 14 septembre 2012 - 02:26:17

Fichier

journal.pbio.1000123.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Zahra Kadri, Ritsuko Shimizu, Osamu Ohneda, Leila Maouche-Chretien, Sylvie Gisselbrecht, et al.. Direct binding of pRb/E2F-2 to GATA-1 regulates maturation and terminal cell division during erythropoiesis.. PLoS Biology, Public Library of Science, 2009, 7 (6), pp.e1000123. 〈10.1371/journal.pbio.1000123〉. 〈inserm-00707647〉

Partager

Métriques

Consultations de la notice

225

Téléchargements de fichiers

116