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PMID: 8508031 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

p53 domains: suppression, transformation, and transactivation.

Gene expression ·Vol. 3 ·No. 1 ·1993-00-00 ·Pages 95-107

Reed M, Wang Y, Mayr G, Anderson ME, Schwedes JF, Tegtmeyer P

Abstract

We investigated the suppression, transformation, and transactivation functions of isolated segments of wild-type murine p53. Intact p53, but no segment of p53, inhibited cellular transformation by the activated ras and adenovirus E1A proteins. We conclude that most of p53 is needed for suppression of cellular proliferation. Nevertheless, the transactivating domain of herpesvirus protein VP16 was able to substitute for the N-terminal transactivating domain of p53 in cellular suppression. Thus, unless the interchanged p53 and VP16 acidic segments share additional functions, transactivation is required for suppression by p53. Interestingly, we found that all p53 segments containing amino acids 320-360 enhanced transformation by ras and E1A. This region has been associated with the oligomerization of p53 (Milner et al., 1991; Sturzbecher et al., 1992). Furthermore, no p53 segment lacking amino acids 320-360 transformed cells. Amino acids 320-360, therefore, may account for the major transforming activity of p53. Intact p53 and chimeric VP16-p53 transactivated the CAT gene under control of a p53-specific promoter, while transforming segments of p53 interfered with transactivation by wild-type p53. Our findings argue that transactivation by p53 is required for cellular suppression and that any nontransactivating p53 that retains the capacity to oligomerize with wild-type p53 would have transformation potential.

Related Genes
p53
MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Division/genetics Cell Transformation, Neoplastic Chromosome Mapping DNA/genetics Gene Expression Genes, p53 Mice Molecular Sequence Data Sequence Tagged Sites Suppression, Genetic Transcriptional Activation
Chemicals
DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Reed M
Department of Microbiology, State University of New York, Stony Brook 11794.
Wang Y
Mayr G
Anderson M E
Schwedes J F
Tegtmeyer P
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Article Info
Journal
Gene expression
Abbr.
Gene Expr
ISSN
1052-2166
Published
1993-00-00
Pages
95-107
Language
English
Region
United States
NLM ID
9200651
PMCID
PMC6081624
Subset
IM
Grants
NCI NIH HHS · P01 CA028146 · United States
NCI NIH HHS · CA-18808 · United States
NCI NIH HHS · CA-28146 · United States
External Links
PubMed source PMC Full Text View journal details
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