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Teh, C.E., Daley, S.R., Enders, A. and Goodnow, C.C. (2010) T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency. Proceedings of the National Academy Sciences of the USA, 107, 14709-14714. doi:10.1073/pnas.1009209107

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• TITLE: The ATPase activity of molecular chaperone HSP60 is inhibited by immunosuppressant mizoribine

  AUTHORS: Masako Tanabe, Ryuichi Ishida, Fumiko Izuhara, Atsushi Komatsuda, Hideki Wakui, Kenichi Sawada, Michiro Otaka, Nobuhiro Nakamura, Hideaki Itoh

  KEYWORDS: HSP60; GroEL; Mizoribine; Inhibition Mechanisms; Conformational Change

  JOURNAL NAME: American Journal of Molecular Biology, Vol.2 No.2, April 28, 2012

  ABSTRACT: The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory mechanisms of HSP60 by mizoribine have not yet been fully understood. In the present study, we investigated the influence of mizoribine on a folding cycle of HSP60 and co-chaperone HSP10. Our results showed that mizoribine inhibited the folding cycle of HSP60/HSP10. The ATPase activity of HSP60/HSP10 was decreased in the presence of mizoribine and the dissociation of HSP10 from HSP-60 was also decreased by mizoribine. The same functions of GroEL and/or GroES were slightly affected by mizoribine. Based on our findings, we discuss the inhibitory mechanisms of HSP60 by mizoribine.