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The BH3-only protein Puma plays an essential role in cytokine deprivation-induced apoptosis of mast cells
Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
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2007 (English)In: Blood, ISSN 0006-4971, Vol. 110, no 9, 3209-3217 p.Article in journal (Refereed) Published
Abstract [en]

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. © 2007 by The American Society of Hematology.

Place, publisher, year, edition, pages
2007. Vol. 110, no 9, 3209-3217 p.
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Medical and Health Sciences
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URN: urn:nbn:se:liu:diva-39823DOI: 10.1182/blood-2007-02-073957Local ID: 51399OAI: oai:DiVA.org:liu-39823DiVA: diva2:260672
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2011-01-11

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Engström, MariaJönsson, Jan-Ingvar

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