PMID- 19444283
OWN - NLM
STAT- MEDLINE
DCOM- 20091103
LR  - 20220316
IS  - 1476-5403 (Electronic)
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 16
IP  - 9
DP  - 2009 Sep
TI  - PUMA is directly activated by NF-kappaB and contributes to TNF-alpha-induced 
      apoptosis.
PG  - 1192-202
LID - 10.1038/cdd.2009.51 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that has an important role 
      in immunity and inflammation by inducing cellular responses such as apoptosis. 
      The transcription factor nuclear factor-kappaB (NF-kappaB) can paradoxically 
      suppress and promote apoptosis in response to TNF-alpha. In this study, we found 
      that p53 upregulated modulator of apoptosis (PUMA), a p53 downstream target and a 
      BH3-only Bcl-2 family member, is directly regulated by NF-kappaB in response to 
      TNF-alpha. TNF-alpha treatment led to increases in PUMA mRNA and protein levels 
      in human colon cancer cells. The induction of PUMA was p53 independent, and 
      mediated by the p65 component of NF-kappaB through a kappaB site in the PUMA 
      promoter. The apoptotic effect of PUMA induction by TNF-alpha was unmasked by 
      depleting the antiapoptotic protein Bcl-X(L). In mice, PUMA was also induced by 
      TNF-alpha in an NF-kappaB-dependent manner. TNF-alpha-induced apoptosis in a 
      variety of tissues and cell types, including small intestinal epithelial cells, 
      hepatocytes, and thymocytes, was markedly reduced in PUMA-deficient mice. 
      Collectively, these results demonstrated that PUMA is a direct target of 
      NF-kappaB and mediates TNF-alpha-induced apoptosis in vitro and in vivo.
FAU - Wang, P
AU  - Wang P
AD  - Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer 
      Institute, Pittsburgh, PA 15213, USA.
FAU - Qiu, W
AU  - Qiu W
FAU - Dudgeon, C
AU  - Dudgeon C
FAU - Liu, H
AU  - Liu H
FAU - Huang, C
AU  - Huang C
FAU - Zambetti, G P
AU  - Zambetti GP
FAU - Yu, J
AU  - Yu J
FAU - Zhang, L
AU  - Zhang L
LA  - eng
GR  - CA121105/CA/NCI NIH HHS/United States
GR  - R01 CA121105/CA/NCI NIH HHS/United States
GR  - R01 CA129829-02/CA/NCI NIH HHS/United States
GR  - U01 DK085570-01/DK/NIDDK NIH HHS/United States
GR  - U01 DK085570/DK/NIDDK NIH HHS/United States
GR  - R01 CA129829/CA/NCI NIH HHS/United States
GR  - R01 CA129829-01A1/CA/NCI NIH HHS/United States
GR  - CA106348/CA/NCI NIH HHS/United States
GR  - R01 CA106348/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 - 20090515
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BBC3 protein, human)
RN  - 0 (BH3 Interacting Domain Death Agonist Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-X Protein)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Apoptosis Regulatory Proteins/genetics/*metabolism
MH  - BH3 Interacting Domain Death Agonist Protein/metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - Mice
MH  - NF-kappa B/*metabolism
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
MH  - bcl-X Protein/metabolism
PMC - PMC2872087
MID - NIHMS195042
EDAT- 2009/05/16 09:00
MHDA- 2009/11/05 06:00
PMCR- 2010/09/01
CRDT- 2009/05/16 09:00
PHST- 2009/05/16 09:00 [entrez]
PHST- 2009/05/16 09:00 [pubmed]
PHST- 2009/11/05 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - cdd200951 [pii]
AID - 10.1038/cdd.2009.51 [doi]
PST - ppublish
SO  - Cell Death Differ. 2009 Sep;16(9):1192-202. doi: 10.1038/cdd.2009.51. Epub 2009 
      May 15.