title: Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1.
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 degrees C for 20 min) resulted in inhibition of H(2)O(2)-induced activation of apoptosis signal-regulating kinase 1 (ASK1). Overexpression of Hsp72 also inhibited H(2)O(2)-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 homo-oligomerization of ASK1 and ASK1-dependent apoptosis. Hsp72 antisense oligonucleotides prevented the inhibitory effects of mild heat shock on H(2)O(2)-induced ASK1 activation and apoptosis. These observations suggest that Hsp72 functions as an endogenous inhibitor of ASK1.
authors.affiliation: National Creative Research Initiative Center for Cell Death. Graduate School of Biotechnology, Korea University, Seoul 136-701, South Korea.
authors.forename: Hee-Sae
authors.initials: HS
authors.lastname: Park
authors.forename: Ssang-Goo
authors.initials: SG
authors.lastname: Cho
authors.forename: Chang Kyun
authors.initials: CK
authors.lastname: Kim
authors.forename: Hyun Sub
authors.initials: HS
authors.lastname: Hwang
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Noh
authors.forename: Mi-Sung
authors.initials: MS
authors.lastname: Kim
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Huh
authors.forename: Myung Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Kanghyun
authors.initials: K
authors.lastname: Ryoo
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Kang
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
authors.forename: Young-Gyu
authors.initials: YG
authors.lastname: Ko
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Eui-Ju
authors.initials: EJ
authors.lastname: Choi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004789:Enzyme Activation; D017930:Genes, Reporter; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D016877:Oxidants; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; C482858:MAP3K5 protein, human; C482859:Map3k5 protein, mouse