期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 27, 期 24, 页码 8713-8728出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01118-07
关键词
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资金
- NHLBI NIH HHS [R01 HL080262] Funding Source: Medline
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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