PMID- 17634411
OWN - NLM
STAT- MEDLINE
DCOM- 20071213
LR  - 20220129
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 110
IP  - 9
DP  - 2007 Nov 1
TI  - The BH3-only protein Puma plays an essential role in cytokine deprivation induced 
      apoptosis of mast cells.
PG  - 3209-17
AB  - 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.
FAU - Ekoff, Maria
AU  - Ekoff M
AD  - Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska 
      Institutet, SE-171 76 Stockholm, Sweden.
FAU - Kaufmann, Thomas
AU  - Kaufmann T
FAU - Engstrom, Maria
AU  - Engstrom M
FAU - Motoyama, Noboru
AU  - Motoyama N
FAU - Villunger, Andreas
AU  - Villunger A
FAU - Jonsson, Jan-Ingvar
AU  - Jonsson JI
FAU - Strasser, Andreas
AU  - Strasser A
FAU - Nilsson, Gunnar
AU  - Nilsson G
LA  - eng
GR  - R01 CA080188/CA/NCI NIH HHS/United States
GR  - Y 212/FWF_/Austrian Science Fund FWF/Austria
GR  - CA 43540/CA/NCI NIH HHS/United States
GR  - CA 80188/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070718
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Bcl2l11 protein, mouse)
RN  - 0 (Cytokines)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (FoxO3 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (PUMA protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 6PLQ3CP4P3 (Etoposide)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Apoptosis/drug effects/*genetics
MH  - Apoptosis Regulatory Proteins/genetics
MH  - Bcl-2-Like Protein 11
MH  - Cell Survival/genetics
MH  - Cells, Cultured
MH  - Clone Cells/cytology/metabolism
MH  - Cytokines/*deficiency
MH  - Etoposide/pharmacology
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors/physiology
MH  - Gene Expression Regulation
MH  - Genes, p53/physiology
MH  - Mast Cells/*cytology/metabolism
MH  - Membrane Proteins/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Protein Structure, Tertiary/physiology
MH  - Proto-Oncogene Proteins/genetics
MH  - Tumor Suppressor Proteins/genetics/metabolism/*physiology
PMC - PMC2200922
EDAT- 2007/07/20 09:00
MHDA- 2007/12/14 09:00
PMCR- 2008/11/01
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2007/12/14 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
PHST- 2008/11/01 00:00 [pmc-release]
AID - S0006-4971(20)42317-1 [pii]
AID - 2007/073957 [pii]
AID - 10.1182/blood-2007-02-073957 [doi]
PST - ppublish
SO  - Blood. 2007 Nov 1;110(9):3209-17. doi: 10.1182/blood-2007-02-073957. Epub 2007 
      Jul 18.