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rdf:type |
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lifeskim:mentions |
umls-concept:C0021666,
umls-concept:C0040649,
umls-concept:C0079419,
umls-concept:C0085180,
umls-concept:C0162493,
umls-concept:C0205263,
umls-concept:C0596988,
umls-concept:C1314792,
umls-concept:C1522492,
umls-concept:C1704241,
umls-concept:C1879547,
umls-concept:C2239176
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pubmed:issue |
33
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pubmed:dateCreated |
2000-9-7
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pubmed:abstractText |
Aflatoxin B1 (AFB1) induced mutation of the p53 gene at codon 249 (p53mt249) is critical during the formation of hepatocellular carcinoma (HCC) following hepatitis B virus (HBV) infection. p53mt249 markedly increases insulin-like growth factor II (IGF-II) transcription largely from promoter 4, accumulating the fetal form of IGF-II. Modulation of the transcription factor binding to IGF-II P4 by wild-type p53 and p53mt249 was identified. Wild-type p53 inhibited binding of transcription factors Sp1 and TBP on the P4 promoter, while p53mt249 enhanced the formation of transcriptional complexes through enhanced DNA-protein (Sp1 or TBP) and protein-protein (Sp1 and TBP) interactions. p53mt249 stimulates transcription factor Sp1 phosphorylation which might be a cause of increased transcription factor binding on the P4 promoter while wild-type p53 does not. Transfection of hepatocytes with p53mt249 impaired induction of apoptosis by the HBV-X protein and TNF-alpha. Therefore, the blocking of apoptosis through enhanced production of IGF-II should provide a favorable opportunity for the selection of transformed hepatocytes. These results explain the molecular basis for the genesis of HCC by p53mt249 which was found to be induced by a potent mutagen, AFB1.
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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/Aflatoxin B1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatitis B Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Mutagens,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TATA-Box Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/hepatitis B virus X protein
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0950-9232
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3717-26
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10949925-Aflatoxin B1,
pubmed-meshheading:10949925-Animals,
pubmed-meshheading:10949925-Apoptosis,
pubmed-meshheading:10949925-Carcinoma, Hepatocellular,
pubmed-meshheading:10949925-Cell Line,
pubmed-meshheading:10949925-Cell Line, Transformed,
pubmed-meshheading:10949925-DNA-Binding Proteins,
pubmed-meshheading:10949925-Drosophila,
pubmed-meshheading:10949925-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:10949925-Gene Expression,
pubmed-meshheading:10949925-Hepatitis B Antigens,
pubmed-meshheading:10949925-Humans,
pubmed-meshheading:10949925-Insulin-Like Growth Factor II,
pubmed-meshheading:10949925-Liver Neoplasms,
pubmed-meshheading:10949925-Mutagenesis,
pubmed-meshheading:10949925-Mutagens,
pubmed-meshheading:10949925-Promoter Regions, Genetic,
pubmed-meshheading:10949925-Sp1 Transcription Factor,
pubmed-meshheading:10949925-TATA-Box Binding Protein,
pubmed-meshheading:10949925-Trans-Activators,
pubmed-meshheading:10949925-Transcription Factors,
pubmed-meshheading:10949925-Transcriptional Activation,
pubmed-meshheading:10949925-Tumor Cells, Cultured,
pubmed-meshheading:10949925-Tumor Necrosis Factor-alpha,
pubmed-meshheading:10949925-Tumor Suppressor Protein p53
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pubmed:year |
2000
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pubmed:articleTitle |
Activation of the insulin-like growth factor II transcription by aflatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma.
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pubmed:affiliation |
Bioscience Research Division, Korea Research Institute of Bioscience and Biotechnology, Yusong, Taejon.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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