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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
39
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pubmed:dateCreated |
2004-9-20
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pubmed:abstractText |
The promyelocytic leukemia gene (PML) encodes a growth/tumor suppressor protein that is essential for the induction of apoptosis in response to various apoptotic signals. The mechanism by which PML plays a role in the regulation of cell death is still unknown. In the current study, we demonstrate that PML negatively regulated the SAPK2/p38 signaling pathway by sequestering p38 from its upstream kinases, MKK3, MKK4, and MKK6, whereas PML did not affect the SAPK1/c-Jun NH(2)-terminal kinase pathway. PML associated with p38 both in vitro and in vivo and the carboxyl terminus of PML mediated the interaction. In contrast to other studies of PML and PML-nuclear bodies (NB), our study shows that the formation of PML-NBs was not required for PML to suppress p38 activity because PML was still able to bind and inhibit p38 activity under the conditions in which PML-NBs were disrupted. In addition, we show that the promotion of Fas-induced cell death by PML correlated with the extent of p38 inhibition by PML, suggesting that PML might regulate apoptosis through manipulating SAPK2/p38 pathways. Our findings define a novel function of PML as a negative regulator of p38 kinase and provide further understanding on the mechanism of how PML induces multiple pathways of apoptosis.
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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/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PML protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203580,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:AhnJin-HyunJH,
pubmed-author:AhnKwangseogK,
pubmed-author:ChoKwangminK,
pubmed-author:ChoSunglimS,
pubmed-author:ChoiEui-JuEJ,
pubmed-author:JinBong-SukBS,
pubmed-author:KimYoungkyunY,
pubmed-author:LeeSeong-OkSO,
pubmed-author:LeeSungwookS,
pubmed-author:LeeSunrayS,
pubmed-author:ParkBoyounB,
pubmed-author:ShinJinwookJ
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pubmed:copyrightInfo |
Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
40994-1003
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15273249-Antigens, CD95,
pubmed-meshheading:15273249-Apoptosis,
pubmed-meshheading:15273249-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:15273249-Cell Death,
pubmed-meshheading:15273249-Cell Line,
pubmed-meshheading:15273249-Cell Nucleus,
pubmed-meshheading:15273249-Dose-Response Relationship, Drug,
pubmed-meshheading:15273249-Enzyme Inhibitors,
pubmed-meshheading:15273249-Flow Cytometry,
pubmed-meshheading:15273249-Gene Expression Regulation,
pubmed-meshheading:15273249-Glutathione Transferase,
pubmed-meshheading:15273249-HeLa Cells,
pubmed-meshheading:15273249-Humans,
pubmed-meshheading:15273249-Imidazoles,
pubmed-meshheading:15273249-MAP Kinase Kinase 3,
pubmed-meshheading:15273249-MAP Kinase Kinase 6,
pubmed-meshheading:15273249-Microscopy, Fluorescence,
pubmed-meshheading:15273249-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:15273249-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15273249-Neoplasm Proteins,
pubmed-meshheading:15273249-Nuclear Proteins,
pubmed-meshheading:15273249-Phosphorylation,
pubmed-meshheading:15273249-Plasmids,
pubmed-meshheading:15273249-Protein Binding,
pubmed-meshheading:15273249-Protein Structure, Tertiary,
pubmed-meshheading:15273249-Protein-Tyrosine Kinases,
pubmed-meshheading:15273249-Pyridines,
pubmed-meshheading:15273249-Signal Transduction,
pubmed-meshheading:15273249-Transcription Factors,
pubmed-meshheading:15273249-Transfection,
pubmed-meshheading:15273249-Tumor Suppressor Proteins,
pubmed-meshheading:15273249-Ultraviolet Rays,
pubmed-meshheading:15273249-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
Promyelocytic leukemia is a direct inhibitor of SAPK2/p38 mitogen-activated protein kinase.
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pubmed:affiliation |
College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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