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PMID: 8415687 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Modulation of cell proliferation and gene expression by a p53-estrogen receptor hybrid protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 20 ·1993-10-15 ·Pages 9252-6

Roemer K, Friedmann T

Abstract

We report that p53her, a chimeric protein consisting of the complete human wild-type p53 and the human estrogen receptor hormone-binding domain, strongly suppresses proliferation and induces characteristic morphological changes in Saos-2 human osteosarcoma cells when induced by 17 beta-estradiol. In contrast, p53her constitutively transactivates a p53-responsive promoter in transfection assays, so that transactivation is not regulated by estradiol. However, coexpression of p53her and oncoprotein MDM-2, which associates with and presumably inactivates p53, results in suppression of p53her-mediated transactivation in the absence, but not the presence, of estradiol. Similarly, p53her induces expression of an endogenous MDM-2 transcript only in the presence of estradiol. These results suggest a correlation between the growth suppressor function of p53her and release of a transactivation block mediated by MDM-2.

MeSH Terms
Amino Acid Sequence Base Sequence Cell Division Estradiol/pharmacology Gene Expression Regulation/drug effects Humans In Vitro Techniques Molecular Sequence Data Receptors, Estrogen/metabolism Recombinant Fusion Proteins/metabolism Tamoxifen/pharmacology Transcription Factors/metabolism Transcription, Genetic Tumor Cells, Cultured Tumor Suppressor Protein p53/metabolism
Chemicals
Receptors, Estrogen Recombinant Fusion Proteins Transcription Factors Tumor Suppressor Protein p53 Tamoxifen Estradiol
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Roemer K
Center for Molecular Genetics, University of California, San Diego, La Jolla 92093-0634.
Friedmann T
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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.90.20.9252
Published
1993-10-15
Pages
9252-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47545
Subset
IM
Grants
NCI NIH HHS · CA58317 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.20.9252 PMC Full Text View journal details
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