Heat shock protein 25 or inducible heat shock protein 70 activates heat shock factor 1: Dephosphorylation on serine 307 through inhibition of ERK1/2 phosphorylation

Haeng Ran Seo, Da Yeon Chung, Yoon Jin Lee, Dae Hoon Lee, Jong Il Kim, Sangwoo Bae, Hee Yong Chung, Su Jae Lee, Dooil Jeoung, Yun Sil Lee

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33 Scopus citations

Abstract

The expression of heat shock proteins (HSPs) is known to be increased via activation of heat shock factor 1 (HSF1), and excess expression of HSPs exerts feedback inhibition of HSF1. However, the molecular mechanism to modulate such relationships between HSPs and HSF1 is not clear. In the present study, we show that stable transfection of either Hsp25 or inducible Hsp70 (Hsp70i) increased expression of endogenous HSPs such as HSP25 and HSP70i through HSF1 activation. However, these phenomena were abolished when the dominant negative Hsf1 mutant was transfected to HSP25 or HSP70i overexpressed cells. Moreover, the increased HSF1 activity by either HSP25 or HSP70i was found to result from dephosphorylation of HSF1 on serine 307 that increased the stability of HSF1. Either HSP25 or HSP70i inhibited ERK1/2 phosphorylation because of increased MKP1 phosphorylation by direct interaction of these HSPs with MKP1. Treatment of HOS and NCI-H358 cells, which showed high expressions of endogenous HSF1, with small interfering RNA (siRNA) of either HSP27 (siHSP27) or HSP70i (siHSP70i) inhibited both HSP27 and HSP70i proteins; this was because of increased ERK1/2 phosphorylation and serine phosphorylation of HSF1. The results, therefore, suggested that when the HSF1 protein level was high in cancer cells, excess expression of HSP27 or HSP70i strongly facilitates the expression of HSP proteins through HSF1 activation, resulting in severe radio- or chemoresistance.

Original languageEnglish
Pages (from-to)17220-17227
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number25
DOIs
StatePublished - 23 Jun 2006

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