Article
- The EMBO Journal (2004) 23, 4319 - 4329
- doi:10.1038/sj.emboj.7600432
Published online: 30 September 2004
Subject Categories:
The Rb tumor suppressor is required for stress erythropoiesis
Benjamin T Spike1,2, Alexandra Dirlam1,3, Benjamin C Dibling1, James Marvin4, Bart O Williams5, Tyler Jacks6,7 and Kay F Macleod1,2,3
- The Ben May Institute for Cancer Research, The University of Chicago, Chicago, IL, USA
- The Committee on Cancer Biology, University of Chicago, Chicago, IL, USA
- The Committee on Immunology, University of Chicago, Chicago, IL, USA
- The Flow Cytometry Laboratory, University of Chicago, Chicago, IL, USA
- Van Andel Research Institute, Grand Rapids, MI, USA
- The Department of Biology & Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
- The Howard Hughes Medical Institutes, Chevy Chase, MD, USA
Correspondence to:
Kay F Macleod, The Ben May Institute for Cancer Research, The University of Chicago, The Knapp Medical Research Building, R118, 924 East 57th Street, Chicago, IL 60637, USA. Tel.: +1 773 834 8309; Fax: +1 773 702 3701; E-mail: kmacleod@huggins.bsd.uchicago.edu
Received 29 March 2004; Accepted 9 September 2004
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.
Keywords:
- cell cycle,
- enucleation,
- erythropoiesis,
- homeostasis,
- pRb
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