title: HSP25 inhibits protein kinase C delta-mediated cell death through direct interaction.
abstract: Heat shock protein 25 (HSP25) interferes negatively with apoptosis through several pathways that involve its direct interaction with cytochrome c or Akt. Here we show that HSP25 inhibits protein kinase C (PKC) delta-mediated cell death through direct interaction. HSP25 binds to kinase-active PKCdelta to inhibit its kinase activity and translocation to the membrane, which results in reduced cell death. Deletion constructs of HSP25 and PKCdelta identified amino acids 90-103 of HSP25 and the C-terminal V5 region of PKCdelta as binding sites. In addition, the interaction between HSP25 and PKCdelta induced HSP25 phosphorylation at Ser-15 and Ser-86, and these phosphorylations permitted HSP25 release from PKCdelta. Based on these observations, we propose that after PKCdelta activation, HSP25 binds to the exposed V5 region of PKCdelta. This novel function of HSP25 accounts for its cytoprotective properties via the inhibition of PKCdelta and the enhancement of HSP25 phosphorylation.
authors.affiliation: Laboratory of Radiation Effect and Laboratory of Experimental Radiation Therapeutics, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Dae-Hoon
authors.initials: DH
authors.lastname: Lee
authors.forename: Chul-Koo
authors.initials: CK
authors.lastname: Cho
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Bae
authors.forename: Gil-Ja
authors.initials: GJ
authors.lastname: Jhon
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Soh
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051745:Protein Kinase C-delta
chemical_list: D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C497259:Prkcd protein, mouse; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta