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The BH3-only protei...
The BH3-only protein Puma plays an essential role in cytokine deprivation-induced apoptosis of mast cells
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- Ekoff, Maria (author)
- Karolinska Institutet
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Kaufmann, Thomas (author)
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- Engström, Maria, 1973- (author)
- Linköpings universitet,Hälsouniversitetet,Avdelningen för medicinsk cellbiologi
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Motoyama, Noboru (author)
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Villunger, Andreas (author)
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- Jönsson, Jan-Ingvar, 1961- (author)
- Linköpings universitet,Hälsouniversitetet,Avdelningen för medicinsk cellbiologi
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Strasser, Andreas (author)
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- Nilsson, Gunnar (author)
- Karolinska Institutet
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(creator_code:org_t)
- American Society of Hematology, 2007
- 2007
- English.
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:9, s. 3209-3217
- Related links:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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