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PMID: 1448088 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding.

Molecular and cellular biology ·Vol. 12 ·No. 12 ·1992-12-00 ·Pages 5581-92

Shaulian E, Zauberman A, Ginsberg D, Oren M

Abstract

Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized with endogenous cell p53. To determine the relevance of oligomerization for transformation, miniproteins containing C-terminal portions of p53 were generated. These miniproteins, although carrying no point mutation, transformed at least as efficiently as full-length mutant p53. Transforming activity was coupled with the ability to oligomerize with wild-type p53, as well as with the ability to abrogate sequence-specific DNA binding by coexpressed wild-type p53. These findings suggest that p53-mediated transformation may operate through a dominant negative mechanism, involving the generation of DNA binding-incompetent oligomers.

Related Genes
p53
MeSH Terms
Animals Base Sequence Cell Line Cell Transformation, Neoplastic/genetics DNA/metabolism Genes, p53 Molecular Sequence Data Mutation Precipitin Tests Rats Tumor Suppressor Protein p53/genetics,metabolism
Chemicals
Tumor Suppressor Protein p53 DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shaulian E
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Zauberman A
Ginsberg D
Oren M
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76 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.12.5581-5592.1992
Published
1992-12-00
Pages
5581-92
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360497
Subset
IM
Grants
NCI NIH HHS · R01 CA40099 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.12.5581-5592.1992 PMC Full Text View journal details
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