Heat shock protein Hsp72 is a negative regulator of apoptosis signal-regulating kinase 1

Hee Sae Park, Ssang Goo Cho, Chang Kyun Kim, Hyun Sub Hwang, Kyung Tae Noh, Mi Sung Kim, Sung Ho Huh, Myung Jin Kim, Kanghyun Ryoo, Eun Kyung Kim, Woo Jin Kang, Jae Seon Lee, Jeong Sun Seo, Young Gyu Ko, Sunghoon Kim, Eui Ju Choi

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134 Citations (Scopus)

Abstract

Heat shock protein 72 (Hsp72) is thought to protect cells against cellular stress. The protective role of Hsp72 was investigated by determining the effect of this protein on the stress-activated protein kinase signaling pathways. Prior exposure of NIH 3T3 cells to mild heat shock (43°C for 20 min) resulted in inhibition of H2O2-induced activation of apoptosis signal-regulating kinase 1 (ASK1). Overexpression of Hsp72 also inhibited H2O2-induced activation of ASK1 as well as that of downstream kinases in the p38 mitogen-activated protein kinase (MAPK) signaling cascade. Recombinant Hsp72 bound directly to ASK1 and inhibited ASK1 activity in vitro. Furthermore, coimmunoprecipitation analysis revealed a physical interaction between endogenous Hsp72 and ASK1 in NIH 3T3 cells exposed to mild heat shock. Hsp72 blocked both the homooligomerization of ASK1 and ASK1-dependent apoptosis. Hsp72 antisense oligonucleotides prevented the inhibitory effects of mild heat shock on H2O2-induced ASKI activation and apoptosis. These observations suggest that Hsp72 functions as an endogenous inhibitor of ASK1.

Original languageEnglish
Pages (from-to)7721-7730
Number of pages10
JournalMolecular and cellular biology
Volume22
Issue number22
DOIs
Publication statusPublished - 2002 Nov 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Park, H. S., Cho, S. G., Kim, C. K., Hwang, H. S., Noh, K. T., Kim, M. S., Huh, S. H., Kim, M. J., Ryoo, K., Kim, E. K., Kang, W. J., Lee, J. S., Seo, J. S., Ko, Y. G., Kim, S., & Choi, E. J. (2002). Heat shock protein Hsp72 is a negative regulator of apoptosis signal-regulating kinase 1. Molecular and cellular biology, 22(22), 7721-7730. https://doi.org/10.1128/MCB.22.22.7721-7730.2002