Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response.
The 90-kDa heat shock protein, HSP90, is an abundant molecular chaperone which functions in cellular homeostasis in prokaryotes and eukaryotes. It is well known that HSP90 plays a critical and indispensable role in regulating cell growth through modulations of various signal transduction pathways, but its roles in cell cycle control are not so well known. We transferred human HSP90 (wild-type or mutated types) expression vectors into NIH-3T3 cells in order to study certain functions of HSP90 in the cell cycle and cell growth under physiological conditions. We found that the exogenous expression of HSP90 (wild-type) induced a decrease in cell growth via retardation of the G1/S transition. The inhibition of cell growth was caused by reduced expressions of cyclin D3 and cyclin A mRNA and protein. On the other hand, no stable transfectants with the three types of mutated HSP90 were obtained. Unexpectedly, exogenous HSP90 expression impaired the heat shock response by inhibiting both heat shock transcription factor 1(HSF1) activation and transportation of HSF1 into the nucleus. The HSF1 function was disrupted by the direct association between HSF1 and exogenous HSP90, which was present as a monomer. These results reveal important roles of HSP90 in cell cycle control and in the stress response of nontransformed cells.
Zhao
Chen
C
Department of Pathology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Hashiguchi
Akinori
A
Kondoh
Kensuke
K
Du
Wenlin
W
Hata
Jun-ichi
J
Yamada
Taketo
T
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D006801:Humans; D007700:Kinetics; D051379:Mice; D014157:Transcription Factors; D014162:Transfection
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors