HSP25 inhibits protein kinase C delta-mediated cell death through direct interaction.
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.
Lee
Yoon-Jin
YJ
Laboratory of Radiation Effect and Laboratory of Experimental Radiation Therapeutics, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Lee
Dae-Hoon
DH
Cho
Chul-Koo
CK
Bae
Sangwoo
S
Jhon
Gil-Ja
GJ
Lee
Su-Jae
SJ
Soh
Jae-Won
JW
Lee
Yun-Sil
YS
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
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