Document Detail


PUMA, a potent killer with or without p53.
MedLine Citation:
PMID:  19641508     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PUMA (p53 upregulated modulator of apoptosis) is a Bcl-2 homology 3 (BH3)-only Bcl-2 family member and a critical mediator of p53-dependent and -independent apoptosis induced by a wide variety of stimuli, including genotoxic stress, deregulated oncogene expression, toxins, altered redox status, growth factor/cytokine withdrawal and infection. It serves as a proximal signaling molecule whose expression is regulated by transcription factors in response to these stimuli. PUMA transduces death signals primarily to the mitochondria, where it acts indirectly on the Bcl-2 family members Bax and/or Bak by relieving the inhibition imposed by antiapoptotic members. It directly binds and antagonizes all known antiapoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. PUMA ablation or inhibition leads to apoptosis deficiency underlying increased risks for cancer development and therapeutic resistance. Although elevated PUMA expression elicits profound chemo- and radiosensitization in cancer cells, inhibition of PUMA expression may be useful for curbing excessive cell death associated with tissue injury and degenerative diseases. Therefore, PUMA is a general sensor of cell death stimuli and a promising drug target for cancer therapy and tissue damage.
Authors:
J Yu; L Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Oncogene     Volume:  27 Suppl 1     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2009-07-30     Completed Date:  2009-09-21     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  S71-83     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis / physiology
Apoptosis Regulatory Proteins / genetics,  physiology*
Conserved Sequence
DNA Damage
Drug Resistance, Neoplasm / physiology
Gene Expression Regulation
Humans
Infection / metabolism
Mice
Mitochondria / metabolism
Molecular Sequence Data
Neoplasms / pathology,  therapy
Oxidative Stress
Proto-Oncogene Proteins / genetics,  physiology*
Proto-Oncogene Proteins c-bcl-2 / physiology
Radiation Tolerance / physiology
Sequence Alignment
Sequence Homology, Amino Acid
Stress, Physiological / physiology
Transcription Factors / physiology
Tumor Suppressor Protein p53 / physiology
Tumor Suppressor Proteins / genetics,  physiology
Grant Support
ID/Acronym/Agency:
CA129829/CA/NCI NIH HHS; P50CA097190/CA/NCI NIH HHS; R01 CA106348/CA/NCI NIH HHS; R01 CA106348-01/CA/NCI NIH HHS; R01 CA106348-02/CA/NCI NIH HHS; R01 CA106348-03/CA/NCI NIH HHS; R01 CA106348-04/CA/NCI NIH HHS; R01 CA106348-05/CA/NCI NIH HHS; R01 CA121105/CA/NCI NIH HHS; R01 CA121105-01A1/CA/NCI NIH HHS; R01 CA121105-02/CA/NCI NIH HHS; R01 CA121105-03/CA/NCI NIH HHS; R01 CA129829/CA/NCI NIH HHS; R01 CA129829-01A1/CA/NCI NIH HHS; R01 CA129829-02/CA/NCI NIH HHS; U01 DK085570/DK/NIDDK NIH HHS; U01 DK085570-01/DK/NIDDK NIH HHS; U19-A1068021//PHS HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BBC3 protein, human; 0/PUMA protein, mouse; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins
Comments/Corrections

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