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PMID: 8590809 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

A role for Hsp90 in retinoid receptor signal transduction.

Molecular biology of the cell ·Vol. 6 ·No. 12 ·1995-12-00 ·Pages 1833-42

Holley SJ, Yamamoto KR

Abstract

The ubiquitous heat shock protein Hsp90 appears to participate directly in the function of a broad range of cellular signal transduction components, including steroid hormone receptors; however, an evolutionarily related subclass of intracellular receptors, exemplified by the retinoid receptors RAR and RXR, had been inferred from biochemical studies to function independently of Hsp90. To examine this issue genetically, we measured mammalian and avian retinoid receptor activity in a Saccharomyces cerevisiae strain in which the expression of the yeast Hsp90 homologue could be conditionally repressed approximately 20-fold relative to wild type. We tested transcriptional activation by RAR or RXR-RAR, from two types of retinoic acid response elements, triggered by three different agonist ligands. In every condition, we found that activation was severely compromised under conditions of low Hsp90 expression. We showed that the defect was in signal transduction rather than transcription activation per se, and that high affinity hormone binding was abolished in extracts of cells producing low levels of Hsp90. We suggest that Hsp90 may function in at least one step of signal transduction by all members of the intracellular receptor superfamily.

MeSH Terms
Animals Base Sequence Chickens Cloning, Molecular Desoxycorticosterone/pharmacology Genotype HSP90 Heat-Shock Proteins/biosynthesis,physiology Humans Mammals Molecular Sequence Data Mutagenesis, Insertional Oligodeoxyribonucleotides Plasmids Promoter Regions, Genetic Receptors, Retinoic Acid/biosynthesis,physiology Recombinant Proteins/biosynthesis,metabolism Retinoid X Receptors Saccharomyces cerevisiae/physiology Signal Transduction Transcription Factors/biosynthesis,physiology Transcriptional Activation Tretinoin/pharmacology beta-Galactosidase/analysis,biosynthesis
Chemicals
HSP90 Heat-Shock Proteins Oligodeoxyribonucleotides Receptors, Retinoic Acid Recombinant Proteins Retinoid X Receptors Transcription Factors Desoxycorticosterone Tretinoin beta-Galactosidase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Holley S J
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA.
Yamamoto K R
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.6.12.1833
Published
1995-12-00
Pages
1833-42
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC301336
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.6.12.1833 PMC Full Text View journal details
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