Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90

Ishida, Ryuichi; Takaoka, Yuka; Yamamoto, Soh; Miyazaki, Toshio; Otaka, Michiro; Watanabe, Sumio; Komatsuda, Atushi; Wakui, Hideki; Sawada, Ken-ichi; Kubota, Hiroshi; Itoh, Hideaki

doi:10.1016/j.febslet.2008.10.029

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Volume 582, Issue 28 , Pages 3879-3883, 26 November 2008

Cisplatin differently affects amino terminal and carboxyl terminal domains of HSP90

Edited by Gianni Cesareni

Ryuichi Ishida
- Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan
Yuka Takaoka
- Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan
Soh Yamamoto
- Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan
Toshio Miyazaki
- Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan
Michiro Otaka
- Department of Gastroenterology, Juntendo University School of Medicine, 113-8421, Japan
Sumio Watanabe
- Department of Gastroenterology, Juntendo University School of Medicine, 113-8421, Japan
Atushi Komatsuda
- Department of Internal Medicine, Akita University School of Medicine, Akita 010-8543, Japan
Hideki Wakui
- Department of Internal Medicine, Akita University School of Medicine, Akita 010-8543, Japan
Ken-ichi Sawada
- Department of Internal Medicine, Akita University School of Medicine, Akita 010-8543, Japan
Hiroshi Kubota
- Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan
Hideaki Itoh
- Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegata Gakuen Town, Akita 010-8502, Japan
- Corresponding author. Fax: +81 889 3041.

Received 9 September 2008; received in revised form 13 October 2008; accepted 14 October 2008. published online 24 October 2008.

Abstract

The 90-kDa heat shock protein (HSP90) is a molecular chaperone that assists in the folding and assembly of proteins in the cytosol. We previously demonstrated that the antineoplastic reagent, cisplatin, inhibits the aggregation prevention activity of mammalian HSP90. We now show that cisplatin binds both the amino terminal and carboxyl terminal domains of the human HSP90 and differently affects these two domains. Cisplatin blocks the aggregation prevention activity of HSP90C, but not HSP90N. In contrast, cisplatin induces a conformational change in HSP90N, but not HSP90C. These results indicate that cisplatin modulates the HSP90 activities through two different mechanisms using the two distinct binding sites of the HSP90 molecule.

Keywords: HSP90, Molecular chaperone, Cisplatin, Aggregation prevention, Conformational change