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

Eitan Shaulian, Arie Zauberman, Doron Ginsberg, Moshe Oren

Research output: Contribution to journalArticlepeer-review

346 Scopus citations

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.

Original languageEnglish
Pages (from-to)5581-5592
Number of pages12
JournalMolecular and Cellular Biology
Volume12
Issue number12
StatePublished - Dec 1992
Externally publishedYes

Funding

FundersFunder number
National Cancer InstituteR01CA040099

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