The BH3-only protein Puma plays an essential role in cytokine deprivation–induced apoptosis of mast cells
In: Blood, Jg. 110 (2007-11-01), S. 3209-3217
Online
unknown
Zugriff:
Mast cells play critical roles in the regulation of inflammation. One characteristic feature of mast cells is their relatively long lifespan in vivo. Members of the Bcl-2 protein family are regulators of cell survival and apoptosis, where the BH3-only proteins are critical proapoptotic proteins. In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid, and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue–like mast cells (CTLMCs). We demonstrate that Puma is critical for the induction of mast-cell death following cytokine deprivation and treatment with the DNA-damaging agent etoposide in MLMCs and CTLMCs. Using p53−/− mast cells, we found that cytokine deprivation–induced apoptosis, in contrast to that elicited by etoposide, is p53-independent. Interestingly, mast cells deficient in FOXO3a, previously proposed as a transcription factor for Puma induction in response to growth factor deprivation, were markedly resistant to cytokine withdrawal compared with wild-type cells. Moreover, overexpression of phosphorylation-deficient, constitutively active FOXO3a caused an up-regulation of Puma. In conclusion, our data demonstrate a pivotal role for Puma in the regulation of cytokine deprivation–induced mast-cell apoptosis and suggest a plausible role for Puma in the regulation of mast cell numbers in vivo.
Titel: |
The BH3-only protein Puma plays an essential role in cytokine deprivation–induced apoptosis of mast cells
|
---|---|
Autor/in / Beteiligte Person: | Motoyama, Noboru ; Villunger, Andreas ; Strasser, Andreas ; Engström, Maria ; Ekoff, Maria ; Nilsson, Gunnar ; Kaufmann, Thomas ; Jönsson, Jan-Ingvar |
Link: | |
Zeitschrift: | Blood, Jg. 110 (2007-11-01), S. 3209-3217 |
Veröffentlichung: | American Society of Hematology, 2007 |
Medientyp: | unknown |
ISSN: | 1528-0020 (print) ; 0006-4971 (print) |
DOI: | 10.1182/blood-2007-02-073957 |
Schlagwort: |
|
Sonstiges: |
|