Journal
GENES & DEVELOPMENT
Volume 22, Issue 4, Pages 463-475Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1627208
Keywords
Rb; cell cycle; cell differentiation; crythropoiesis; hematopoiesis; mitochondrial biogenesis
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
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Regulation of the cell cycle is intimately linked to erythroid differentiation, yet how these processes are coupled is not well understood. To gain insight into this coordinate regulation, we examined the role that the retinoblastoma protein (Rb), a central regulator of the cell cycle, plays in erythropoiesis. We found that Rb serves a cell-intrinsic role and its absence causes ineffective erythropoiesis, with a differentiation block at the transition from early to late erythroblasts. Unexpectedly, in addition to a failure to properly exit the cell cycle, mitochondrial biogenesis fails to be up-regulated concomitantly, contributing to this differentiation block. The link between erythropoiesis and mitochondrial function was validated by inhibition of mitochondrial biogenesis. Erythropoiesis in the absence of Rb resembles the human myelodysplastic syndromes, where defects in cell cycle regulation and mitochondrial function frequently occur. Our work demonstrates how these seemingly disparate pathways play a role in coordinately regulating cellular differentiation.
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