Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response

Chen Zhao, Akinori Hashiguchi, Kensuke Kondoh, Wenlin Du, Jun Ichi Hata, Taketo Yamada

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)200-214
Number of pages15
JournalExperimental Cell Research
Volume275
Issue number2
DOIs
Publication statusPublished - 2002

Fingerprint

Heat-Shock Response
Heat-Shock Proteins
Cell Cycle
HSP90 Heat-Shock Proteins
Growth
Cell Cycle Checkpoints
Cyclin D3
Cyclin A
NIH 3T3 Cells
Molecular Chaperones
Eukaryota
Signal Transduction
Homeostasis
Messenger RNA
heat shock transcription factor
Proteins

Keywords

  • Cell cycle
  • Cyclin
  • Heat shock protein
  • Heat shock response
  • HSF1
  • HSP90

ASJC Scopus subject areas

  • Cell Biology

Cite this

Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response. / Zhao, Chen; Hashiguchi, Akinori; Kondoh, Kensuke; Du, Wenlin; Hata, Jun Ichi; Yamada, Taketo.

In: Experimental Cell Research, Vol. 275, No. 2, 2002, p. 200-214.

Research output: Contribution to journalArticle

Zhao, Chen ; Hashiguchi, Akinori ; Kondoh, Kensuke ; Du, Wenlin ; Hata, Jun Ichi ; Yamada, Taketo. / Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response. In: Experimental Cell Research. 2002 ; Vol. 275, No. 2. pp. 200-214.
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