Kaoru Yamamoto

Publications (2)10.75 Total impact

• Source

  Available from: Ramachandran Prakasam

  Article: Heat shock factor 2 is required for maintaining proteostasis against febrile-range thermal stress and polyglutamine aggregation.

  Toyohide Shinkawa, Ke Tan, Mitsuaki Fujimoto, Naoki Hayashida, Kaoru Yamamoto, Eiichi Takaki, Ryosuke Takii, Ramachandran Prakasam, Sachiye Inouye, Valerie Mezger, Akira Nakai
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  ABSTRACT: Heat shock response is characterized by the induction of heat shock proteins (HSPs), which facilitate protein folding, and non-HSP proteins with diverse functions, including protein degradation, and is regulated by heat shock factors (HSFs). HSF1 is a master regulator of HSP expression during heat shock in mammals, as is HSF3 in avians. HSF2 plays roles in development of the brain and reproductive organs. However, the fundamental roles of HSF2 in vertebrate cells have not been identified. Here we find that vertebrate HSF2 is activated during heat shock in the physiological range. HSF2 deficiency reduces threshold for chicken HSF3 or mouse HSF1 activation, resulting in increased HSP expression during mild heat shock. HSF2-null cells are more sensitive to sustained mild heat shock than wild-type cells, associated with the accumulation of ubiquitylated misfolded proteins. Furthermore, loss of HSF2 function increases the accumulation of aggregated polyglutamine protein and shortens the lifespan of R6/2 Huntington's disease mice, partly through αB-crystallin expression. These results identify HSF2 as a major regulator of proteostasis capacity against febrile-range thermal stress and suggest that HSF2 could be a promising therapeutic target for protein-misfolding diseases.
  Molecular biology of the cell 08/2011; 22(19):3571-83. · 5.98 Impact Factor
• Article: Heat shock transcription factor 1 is required for maintenance of ciliary beating in mice.

  Eiichi Takaki, Mitsuaki Fujimoto, Takashi Nakahari, Shigenobu Yonemura, Yoshihiko Miyata, Naoki Hayashida, Kaoru Yamamoto, Richard B Vallee, Tsuyoshi Mikuriya, Kazuma Sugahara, Hiroshi Yamashita, Sachiye Inouye, Akira Nakai
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  ABSTRACT: Heat shock transcription factors (HSFs) maintain protein homeostasis through regulating expression of heat shock proteins, especially in stressed conditions. In addition, HSFs are involved in cellular differentiation and development by regulating development-related genes, as well as heat shock genes. Here, we showed chronic sinusitis and mild hydrocephalus in postnatal HSF1-null mice, which are associated with impaired mucociliary clearance and cerebrospinal flow, respectively. Analysis of ciliary beating revealed that the amplitude of the beating was significantly reduced, and ciliary beat frequencies were lower in the respiratory epithelium, ependymal cells, oviduct, and trachea of HSF1-null mice than those of wild-type mice. Cilia possess a common axonema structure composed of microtubules of alpha- and beta-tubulin. We found a marked reduction in alpha- and ciliary betaiv-tubulin in the HSF1-null cilia, which is developmentally associated with reduced Hsp90 expression in HSF1-null mice. Treatment of the respiratory epithelium with geldanamycin resulted in rapid reduction of ciliary beating in a dose-dependent manner. Furthermore, Hsp90 was physically associated with ciliary betaiv-tubulin, and Hsp90 stabilizes tubulin polymerization in vitro. These results indicate that HSF1 is required to maintain ciliary beating in postnatal mice, probably by regulating constitutive expression of Hsp90 that is important for tubulin polymerization.
  Journal of Biological Chemistry 01/2008; 282(51):37285-92. · 4.77 Impact Factor