title: PKCδ promotes etoposide-induced cell death by phosphorylating Hsp27 in HeLa cells.
abstract: We investigated the regulation of Hsp27 phosphorylation by protein kinase C δ (PKCδ) during etoposide-induced apoptosis. The phosphorylation of Hsp27 at Ser78 was temporally correlated with the proteolytic activation of PKCδ during apoptosis. Hsp27 phosphorylation was dependent on the activity of PKCδ since treatment with rottlerin, a chemical inhibitor of PKCδ, or overexpression of a PKCδ dominant negative mutant abolished the phosphorylation. In addition, recombinant PKCδ phosphorylated Hsp27 at Ser78 in vitro. Moreover, caspase-3 was specifically activated following Hsp27 phosphorylation at Ser78. Pull-down assays using a phosphomimetic Hsp27 mutant revealed that binding between Hsp27 and cytochrome c was abolished by the phosphorylation. These results suggest that Hsp27 dissociates from cytochrome c following PKCδ-mediated phosphorylation at Ser78, which allows formation of the apoptosome and stimulates apoptotic progression.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Joon-Seok
authors.initials: JS
authors.lastname: Choi
authors.forename: Jeong-In
authors.initials: JI
authors.lastname: Oh
authors.forename: Miae
authors.initials: M
authors.lastname: Na
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Joo
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051745:Protein Kinase C-delta / Q000378:metabolism*; D059748:Proteolysis; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; D011994:Recombinant Proteins; D012694:Serine; D005047:Etoposide; D045304:Cytochromes c; D051745:Protein Kinase C-delta; D053148:Caspase 3