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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2002-11-12
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pubmed:abstractText |
It has become increasingly evident that nitric oxide exerts its effects, in part, by S-nitrosylation of cysteine residues. We tested in vitro whether nitric oxide may indirectly control p53 by S-nitrosylation and inactivation of the p53 negative regulator, Hdm2. Treatment of Hdm2 with a nitric oxide donor inhibits Hdm2-p53 binding, a critical step in Hdm2 regulation of p53. The presence of excess amounts of cysteine or dithiothreitol blocks this inhibition of binding. Moreover, nitric oxide inhibition of Hdm2-p53 binding was found to be reversible. Sulfhydryl sensitivity and reversibility are consistent with nitrosylation. Finally, we have identified a critical cysteine residue that nitric oxide modifies to disrupt Hdm2-p53 binding. This cysteine is proximal to the Hdm2-p53 binding interface and is conserved across species from zebrafish to humans. Mutation of this residue from a cysteine to an alanine does not interfere with binding but rather eliminates the sensitivity of Hdm2 to nitric oxide inactivation.
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pubmed:grant |
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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/1-hydroxy-2-oxo-3,3-bis(2-aminoethyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Dithiothreitol,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/MDM2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Triazenes,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0006-2960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13570-4
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12427017-Amino Acid Sequence,
pubmed-meshheading:12427017-Binding Sites,
pubmed-meshheading:12427017-Cysteine,
pubmed-meshheading:12427017-Dithiothreitol,
pubmed-meshheading:12427017-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:12427017-Glutathione,
pubmed-meshheading:12427017-Glutathione Transferase,
pubmed-meshheading:12427017-Humans,
pubmed-meshheading:12427017-Molecular Sequence Data,
pubmed-meshheading:12427017-Mutagenesis, Site-Directed,
pubmed-meshheading:12427017-Mutation,
pubmed-meshheading:12427017-Neoplasm Proteins,
pubmed-meshheading:12427017-Nuclear Proteins,
pubmed-meshheading:12427017-Protein Binding,
pubmed-meshheading:12427017-Protein Conformation,
pubmed-meshheading:12427017-Proto-Oncogene Proteins,
pubmed-meshheading:12427017-Proto-Oncogene Proteins c-mdm2,
pubmed-meshheading:12427017-Recombinant Fusion Proteins,
pubmed-meshheading:12427017-Sequence Homology, Amino Acid,
pubmed-meshheading:12427017-Triazenes,
pubmed-meshheading:12427017-Tumor Suppressor Protein p53
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pubmed:year |
2002
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pubmed:articleTitle |
Nitric oxide-mediated inhibition of Hdm2-p53 binding.
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pubmed:affiliation |
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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