Linked Life Data

8892752

Source:http://linkedlifedata.com/resource/pubmed/id/8892752

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-12-3
pubmed:abstractText
Recently, our laboratory has found a high incidence (77%) of p53 gene mutations in human functional adrenal tumors. Furthermore, the majority of mutant sites were assembled at codons 100, 102, and 249. These mutation sites are not common, and there have been no studies addressing whether or not these mutants points or mutant styles cause the p53 protein to lose function. It has been well known that p53 is a transcription factor. To examine the transcriptional activities of these mutant p53 genes from patients with functional adrenal tumors, we constructed p53 expression plasmids from tumors and paired adjacent normal adrenal gland tissues, using a transient co-transfection assay with a reporter gene in H358 cells. Wild-type p53 from normal adrenal gland tissues specifically trans-activates the expression of a chloramphenicol acetyltransferase (CAT) reporter gene in H358 cells. Three mutant p53 proteins (at codons 100, 102, and 249, respectively) from tumors showed a >90% loss of transcriptional activity. One mutant at codon 68, other than at hot spots, remained at approximately 65% transcriptional activity. An immunoprecipitation assay showed that the mutant proteins of codon 68 and codon 102 could respond to the three monoclonal antibodies (PAbDO-1, PAb1620, and PAb421), indicating that there were no obvious changes in the antigenicity of the proteins. However, the mutant protein of codon 249 could not respond to the carboxy-terminus-specific antibody PAb421 and conformation-specific antibody PAb1620, indicating that there were some obvious changes in the conformation of the mutant proteins. The mutant protein of codon 100 could not be detected by immunoprecipitation assay but could be analyzed by Western blot. In a further study using a DNA-binding assay, it was shown that the loss of transcriptional activity was caused by the loss of DNA-binding ability. These results show that the p53 mutants, derived from functional adrenal tumors, actually lost DNA-binding ability and decreased the transcriptional activity. However, the role of the mutant protein in the tumorigenesis of functional adrenal tumors requires further investigation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1044-5498
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
793-803
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8892752-Adrenal Gland Neoplasms, pubmed-meshheading:8892752-Base Sequence, pubmed-meshheading:8892752-Binding Sites, pubmed-meshheading:8892752-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:8892752-DNA Primers, pubmed-meshheading:8892752-DNA-Binding Proteins, pubmed-meshheading:8892752-Genes, Reporter, pubmed-meshheading:8892752-Genes, p53, pubmed-meshheading:8892752-Humans, pubmed-meshheading:8892752-Introns, pubmed-meshheading:8892752-Plasmids, pubmed-meshheading:8892752-Point Mutation, pubmed-meshheading:8892752-Polymerase Chain Reaction, pubmed-meshheading:8892752-Recombinant Proteins, pubmed-meshheading:8892752-Transcription, Genetic, pubmed-meshheading:8892752-Transcriptional Activation, pubmed-meshheading:8892752-Transfection, pubmed-meshheading:8892752-Tumor Suppressor Protein p53
pubmed:year
1996
pubmed:articleTitle
A significant decrease of the transcriptional activity of p53 mutants deriving from human functional adrenal tumors.
pubmed:affiliation
Department of Clinical Pathology, Kaohsiung Medical College, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't