| Autor: |
Rosas M; Department of Pulmonary Diseases H02.128, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands., Birkenkamp KU, Lammers JW, Koenderman L, Coffer PJ |
| Jazyk: |
angličtina |
| Zdroj: |
FEBS letters [FEBS Lett] 2005 Jan 03; Vol. 579 (1), pp. 191-8. |
| DOI: |
10.1016/j.febslet.2004.11.074 |
| Abstrakt: |
Phosphatidylinositol 3-kinase (PI3K) and its effector protein kinase B (PKB/c-akt) have been implicated as critical mediators of cytokine-induced survival signals. In this study, we have utilized an IL-5 dependent hematopoietic cell line (TF-1) to investigate the signaling events involved in cytokine-dependent erythroblast survival. We demonstrate that IL-5 rescues TF-1 cells from apoptosis through a PI3K/PKB-dependent signaling pathway. Cytokine-withdrawal leads to activation of the Forkhead transcription factor FOXO3a and subsequent expression of the pro-apoptotic Bcl-2 family member Bim. Bim is itself sufficient to induce apoptosis in these cells. Importantly, activation of an inducible active FOXO3a mutant is alone sufficient for upregulation of Bim expression and induction of apoptosis. These data define a mechanism by which survival factors inhibit the default apoptotic pathway and can regulate TF-1 erythroblast survival. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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