| PUMA, a potent killer with or without p53. | |
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MedLine Citation:
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PMID: 19641508 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J Yu; L Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Oncogene Volume: 27 Suppl 1 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2009-07-30 Completed Date: 2009-09-21 Revised Date: 2013-03-08 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: S71-83 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 CA121105-01A1/CA/NCI NIH HHS; R01 CA121105-02/CA/NCI NIH HHS; R01 CA121105-03/CA/NCI NIH HHS; R01 CA129829-01A1/CA/NCI NIH HHS; R01 CA129829-02/CA/NCI NIH HHS; R01 CA129829-05/CA/NCI NIH HHS; U01 DK085570-01/DK/NIDDK NIH HHS; U19-A1068021//PHS HHS |
| Chemical | |
Reg. No./Substance:
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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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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