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PMID:10652277
| Citation |
Kieslinger, M, Woldman, I, Moriggl, R, Hofmann, J, Marine, JC, Ihle, JN, Beug, H and Decker, T (2000) Antiapoptotic activity of Stat5 required during terminal stages of myeloid differentiation. Genes Dev. 14:232-44 |
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| Abstract |
Stat5 is activated by multiple receptors of hematopoietic cytokines. To study its role during hematopoiesis, we have generated primary chicken myeloblasts expressing different dominant-negative (dn) alleles of Stat5. This caused a striking inability to generate mature cells, due to massive apoptosis during differentiation. Bcl-2 was able to rescue differentiating cells expressing dnStat5 from apoptosis, suggesting that during cytokine-dependent differentiation the main function of the protein is to ensure cell survival. Our findings with dnStat5-expressing chicken myeloblasts were confirmed with primary hematopoietic cells from Stat5a/Stat5b-deficient mice. Bone marrow cells from these animals displayed a strong increase in apoptotic cell death during GM-CSF-dependent functional maturation in vitro. The antiapoptotic protein Bcl-x was induced by GM-CSF and IL-3 in a Stat5-dependent fashion. Ectopic expression of Bcl-x rescued Stat5-deficient bone marrow cells from apoptosis, indicating that Stat5 promotes the survival of myeloid progenitor cells through its ability to induce transcription of the bcl-x gene. Finally, the recruitment of myeloid cells to inflammatory sites was found strongly impeded in Stat5-deficient mice. Taken together, our findings suggest that Stat5 may promote cytokine-dependent survival and proliferation of differentiating myeloid progenitor cells in stress or pathological situations, such as inflammation. |
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| Keywords |
Alleles; Animals; Apoptosis/genetics; Apoptosis/physiology; Bone Marrow Cells/physiology; Cell Differentiation/genetics; Cell Differentiation/physiology; Cell Division/genetics; Cell Division/physiology; Cell Line, Transformed; Cell Survival; Cells, Cultured; Chickens; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/physiology; Hematopoiesis/genetics; Hematopoiesis/physiology; Inflammation/pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Milk Proteins; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/physiology; STAT5 Transcription Factor; Trans-Activators/biosynthesis; Trans-Activators/deficiency; Trans-Activators/physiology; bcl-X Protein |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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