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PMID: 8756655 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

A mutant p53 that discriminates between p53-responsive genes cannot induce apoptosis.

Molecular and cellular biology ·Vol. 16 ·No. 9 ·1996-09-00 ·Pages 4961-71

Friedlander P, Haupt Y, Prives C, Oren M

Abstract

Human wild-type (wt) p53 can induce apoptosis in transiently transfected H1299 cells maintained at 37 degrees C, whereas tumor-derived mutant forms of p53 (with the mutation Ala-143, His-175, or Trp-248) fail to do so. At 37 degrees C, p53 with a mutation to Ala at amino acid 143 (p53Ala143) was transcriptionally inactive. However, at 32 degrees C, p53Ala143 strongly activated transcription from several physiologically relevant p53-responsive promoters, to extents similar or greater than that of wt p53. Unexpectedly, p53Ala143 was defective in inducing apoptosis in H1299 cells at 32 degrees C. Concomitantly with the loss of apoptotic activity, p53Ala143 was found to be deficient in its ability to activate transcription from the p53-responsive portions of the Bax and insulin-like growth factor-binding protein 3 gene promoters. It is proposed that there may exist distinct classes of p53-responsive promoters, whose ability to be activated by p53 can be regulated differentially. Such differential regulation may have functional consequences for the effects of p53 on cell fate.

MeSH Terms
Apoptosis/genetics Base Sequence Binding Sites Cell Line Genes, Reporter Genes, p53 Humans Molecular Sequence Data Neoplasm Proteins/genetics,physiology Point Mutation Proto-Oncogene Proteins/physiology Proto-Oncogene Proteins c-bcl-2 Recombinant Fusion Proteins/biosynthesis,genetics Regulatory Sequences, Nucleic Acid Transcription, Genetic Tumor Suppressor Protein p53/physiology bcl-2-Associated X Protein
Chemicals
BAX protein, human Neoplasm Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Recombinant Fusion Proteins Tumor Suppressor Protein p53 bcl-2-Associated X Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Friedlander P
Department of Biological Sciences, Columbia University, New York 10027, USA.
Haupt Y
Prives C
Oren M
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.9.4961
Published
1996-09-00
Pages
4961-71
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231498
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.16.9.4961 PMC Full Text View journal details
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