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PMID: 8134338 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sequence-specific transcriptional activation is essential for growth suppression by p53.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 6 ·1994-03-15 ·Pages 1998-2002

Pietenpol JA, Tokino T, Thiagalingam S, el-Deiry WS, Kinzler KW, Vogelstein B

Abstract

Although several biochemical features of p53 have been described, their relationship to tumor suppression remains uncertain. We have compared the ability of p53-derived proteins to act as sequence-specific transcriptional (SST) activators with their ability to suppress tumor cell growth, using an improved growth-suppression assay. Both naturally occurring and in vitro derived mutations that abrogated the SST activity of p53 lost the ability to suppress tumor cell growth. Additionally, the N- and C-terminal ends of p53 were shown to be functionally replaceable with foreign transactivation and dimerization domains, respectively, with concordant preservation of both SST and tumor-suppressive properties. Only the central region of p53, conferring specific DNA binding, was required to suppress growth by such hybrid proteins. The SST activity of p53 thus appeared to be essential for the protein to function as a tumor suppressor.

MeSH Terms
Base Sequence Cell Division/genetics,physiology Cloning, Molecular DNA DNA-Binding Proteins Fungal Proteins/genetics,metabolism Herpes Simplex Virus Protein Vmw65/genetics,metabolism Humans Molecular Sequence Data Mutation Protein Conformation Protein Kinases/genetics,metabolism Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Trans-Activators/genetics,metabolism Transcription, Genetic Transcriptional Activation Tumor Cells, Cultured Tumor Suppressor Protein p53/chemistry,genetics,physiology
Chemicals
DNA-Binding Proteins Fungal Proteins Herpes Simplex Virus Protein Vmw65 Saccharomyces cerevisiae Proteins Trans-Activators Tumor Suppressor Protein p53 DNA Protein Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pietenpol J A
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Tokino T
Thiagalingam S
el-Deiry W S
Kinzler K W
Vogelstein B
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32 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.6.1998
Published
1994-03-15
Pages
1998-2002
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43296
Subset
IM
Grants
NCI NIH HHS · CA09071 · United States
NCI NIH HHS · CA09243 · United States
NCI NIH HHS · CA43400 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.6.1998 PMC Full Text View journal details
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