The BH3-only protein Puma plays an essential role in cytokine deprivation-induced apoptosis of mast cells
- Author(s)
- Ekoff, M; Kaufmann, T; Engstrom, M; Motoyama, N; Villunger, A; Jonsson, JI; Strasser, A; Nilsson, G;
- Details
- Publication Year 2007-11-01,Volume 110,Issue #9,Page 3209-3217
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- 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 wildtype 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.
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- FORKHEAD TRANSCRIPTION FACTOR; BCL-2 FAMILY-MEMBER; IGE-RECEPTOR ACTIVATION; DNA-DAMAGE RESPONSE; FC-EPSILON-RI; GASTROINTESTINAL MUCOSA; PROGENITOR CELLS; FACTOR FKHR-L1; KIT-LIGAND; IN-VIVO
- Publisher's Version
- https://doi.org/10.1182/blood-2007-02-073957
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-11-01 12:00:00