TY - JOUR
T1 - Identification of a minimal transforming domain of p53
T2 - Negative dominance through abrogation of sequence-specific DNA binding
AU - Shaulian, Eitan
AU - Zauberman, Arie
AU - Ginsberg, Doron
AU - Oren, Moshe
PY - 1992/12
Y1 - 1992/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026446686&partnerID=8YFLogxK
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C2 - 1448088
AN - SCOPUS:0026446686
SN - 0270-7306
VL - 12
SP - 5581
EP - 5592
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 12
ER -