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- Title
The Rb tumor suppressor is required for stress erythropoiesis.
- Authors
Spike, Benjamin T; Dirlam, Alexandra; Dibling, Benjamin C; Marvin, James; Williams, Bart O; Jacks, Tyler; Macleod, Kay F
- Abstract
The retinoblastoma tumor suppressor gene plays important roles in cell cycle control, differentiation and survival during development and is functionally inactivated in most human cancers. Early studies using gene targeting in mice suggested a critical role for pRb in erythropoiesis, while more recent experiments have suggested that many of the abnormal embryonic phenotypes in the Rb null mouse result from a defective placenta. To address this controversy and determine whether Rb has cell intrinsic functions in erythropoiesis, we examined the effects of Rb loss on red cell production following acute deletion of pRb in vitro and under different stress conditions in vivo. Under stress conditions, pRb was required to regulate erythroblast expansion and promote red cell enucleation. Acute deletion of Rb in vitro induced erythroid cell cycle and differentiation defects similar to those observed in vivo. These results demonstrate a cell intrinsic role for pRb in stress erythropoiesis and hematopoietic homeostasis that has relevance for human diseases.
- Publication
The EMBO journal, 2004, Vol 23, Issue 21, p4319
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7600432