17923680

pubmed:Citation

24

By assessing the contribution of deregulated E2F activity to erythroid defects in Rb null mice, we have identified E2f-2 as being upregulated in end-stage red cells, where we show it is the major pRb-associated E2f and the predominant E2f detected at key target gene promoters. Consistent with its expression pattern, E2f-2 loss restored terminal erythroid maturation to Rb null red cells, including the ability to undergo enucleation. Deletion of E2f-2 also extended the life span of Rb null mice despite persistent defects in placental development, indicating that deregulated E2f-2 activity in differentiating erythroblasts contributes to the premature lethality of Rb null mice. We show that the aberrant entry of Rb null erythroblasts into S phase at times in differentiation when wild-type erythroblasts are exiting the cell cycle is inhibited by E2f-2 deletion. E2f-2 loss induced cell cycle arrest in both wild-type and Rb null erythroblasts and was associated with increased DNA double-strand breaks. These results implicate deregulated E2f-2 in the cell cycle defects observed in Rb null erythroblasts and reveal a novel role for E2f-2 during terminal red blood cell differentiation. The identification of a tissue-restricted role for E2f-2 in erythropoiesis highlights the nonredundant nature of E2f transcription factor activities in cell growth and differentiation.

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http://linkedlifedata.com/resource/pubmed/journal/8109087

http://linkedlifedata.com/resource/pubmed/chemical/E2F2 Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein

Dec

pubmed-author:DirlamAlexandraA, pubmed-author:MacleodKay FKF, pubmed-author:SpikeBenjamin TBT

27

Y

2009-11-18

2007

Ben May Department for Cancer Research, Gordon Center for Integrative Sciences, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.