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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5604
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pubmed:dateCreated |
2003-1-10
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pubmed:abstractText |
A small molecule, alpha-(trichloromethyl)-4-pyridineethanol (PETCM), was identified by high-throughput screening as an activator of caspase-3 in extracts of a panel of cancer cells. PETCM was used in combination with biochemical fractionation to identify a pathway that regulates mitochondria-initiated caspase activation. This pathway consists of tumor suppressor putative HLA-DR-associated proteins (PHAP) and oncoprotein prothymosin-alpha (ProT). PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation. PETCM relieved ProT inhibition and allowed apoptosome formation at a physiological concentration of deoxyadenosine triphosphate. Elimination of ProT expression by RNA interference sensitized cells to ultraviolet irradiation-induced apoptosis and negated the requirement of PETCM for caspase activation. Thus, this chemical-biological combinatory approach has revealed the regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2'-deoxyadenosine triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/ANP32A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ANP32B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/APAF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptotic Protease-Activating...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Extracts,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyadenine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thymosin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-(trichloromethyl)-4-pyridineet...,
http://linkedlifedata.com/resource/pubmed/chemical/prothymosin alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1095-9203
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pubmed:author |
pubmed-author:BurnsDaveD,
pubmed-author:DonnellyJenniferJ,
pubmed-author:JiangXuejunX,
pubmed-author:KimHyun-EuiHE,
pubmed-author:KofronJamesJ,
pubmed-author:NgShi-ChungSC,
pubmed-author:RosenbergSaulS,
pubmed-author:ShuHongjunH,
pubmed-author:WangXiaodongX,
pubmed-author:ZhangHaichaoH,
pubmed-author:ZhaoYingmingY
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
299
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
223-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12522243-Amino Acid Sequence,
pubmed-meshheading:12522243-Apoptosis,
pubmed-meshheading:12522243-Apoptotic Protease-Activating Factor 1,
pubmed-meshheading:12522243-Caspase 3,
pubmed-meshheading:12522243-Caspase 9,
pubmed-meshheading:12522243-Caspases,
pubmed-meshheading:12522243-Cell Extracts,
pubmed-meshheading:12522243-Cytochrome c Group,
pubmed-meshheading:12522243-Deoxyadenine Nucleotides,
pubmed-meshheading:12522243-Enzyme Activation,
pubmed-meshheading:12522243-HeLa Cells,
pubmed-meshheading:12522243-Humans,
pubmed-meshheading:12522243-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12522243-Mitochondria,
pubmed-meshheading:12522243-Molecular Sequence Data,
pubmed-meshheading:12522243-Neuropeptides,
pubmed-meshheading:12522243-Nuclear Proteins,
pubmed-meshheading:12522243-Protein Precursors,
pubmed-meshheading:12522243-Proteins,
pubmed-meshheading:12522243-Pyridines,
pubmed-meshheading:12522243-RNA Interference,
pubmed-meshheading:12522243-Recombinant Proteins,
pubmed-meshheading:12522243-Signal Transduction,
pubmed-meshheading:12522243-Thymosin,
pubmed-meshheading:12522243-Tumor Suppressor Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway.
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pubmed:affiliation |
Howard Hughes Medical Institute, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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