Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction
- PMID: 10428030
- DOI: 10.1016/s0092-8674(00)81013-2
Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction
Abstract
The erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a-/-5b-/- mice have normal steady-state hematocrit. Here we show that Stat5 is essential for the high erythropoietic rate during fetal development. Stat5a-/-5b-/- embryos are severely anemic; erythroid progenitors are present in low numbers, show higher levels of apoptosis, and are less responsive to Epo. These findings are explained by a crucial role for Stat5 in EpoR's antiapoptotic signaling: it mediates the immediate-early induction of Bcl-X(L) in erythroid cells through direct binding to the Bcl-X promoter.
Similar articles
-
Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts.Blood. 2001 Dec 1;98(12):3261-73. doi: 10.1182/blood.v98.12.3261. Blood. 2001. PMID: 11719363
-
Erythropoietin can induce the expression of bcl-x(L) through Stat5 in erythropoietin-dependent progenitor cell lines.J Biol Chem. 1999 Aug 6;274(32):22165-9. doi: 10.1074/jbc.274.32.22165. J Biol Chem. 1999. PMID: 10428780
-
A novel mechanism of cooperation between c-Kit and erythropoietin receptor. Stem cell factor induces the expression of Stat5 and erythropoietin receptor, resulting in efficient proliferation and survival by erythropoietin.J Biol Chem. 2001 Jan 12;276(2):1099-106. doi: 10.1074/jbc.M007442200. J Biol Chem. 2001. PMID: 11042182
-
Physiology and function of the erythropoietin receptor.Curr Opin Hematol. 1998 May;5(3):171-6. doi: 10.1097/00062752-199805000-00004. Curr Opin Hematol. 1998. PMID: 9664155 Review.
-
A unique role for Stat5 in recovery from acute anemia.J Clin Invest. 2006 Mar;116(3):626-8. doi: 10.1172/JCI27988. J Clin Invest. 2006. PMID: 16511596 Free PMC article. Review.
Cited by
-
Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular mechanisms of action of a novel BCR-JAK2 tyrosine-kinase.PLoS One. 2012;7(2):e32451. doi: 10.1371/journal.pone.0032451. Epub 2012 Feb 27. PLoS One. 2012. PMID: 22384256 Free PMC article.
-
STAT transcription factors in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention.Leukemia. 2014 Feb;28(2):248-57. doi: 10.1038/leu.2013.192. Epub 2013 Jun 25. Leukemia. 2014. PMID: 23797472 Review.
-
Essential role of GATA-4 in cell survival and drug-induced cardiotoxicity.Proc Natl Acad Sci U S A. 2004 May 4;101(18):6975-80. doi: 10.1073/pnas.0401833101. Epub 2004 Apr 20. Proc Natl Acad Sci U S A. 2004. PMID: 15100413 Free PMC article.
-
Feedback regulation of p38 activity via ATF2 is essential for survival of embryonic liver cells.Genes Dev. 2007 Aug 15;21(16):2069-82. doi: 10.1101/gad.430207. Genes Dev. 2007. PMID: 17699753 Free PMC article.
-
The signaling domain of the erythropoietin receptor rescues prolactin receptor-mutant mammary epithelium.Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14241-5. doi: 10.1073/pnas.222549599. Epub 2002 Oct 15. Proc Natl Acad Sci U S A. 2002. PMID: 12381781 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous