title: Identification of a novel protein kinase Cδ-Smac complex that dissociates during paclitaxel-induced cell death.
abstract: Protein kinase C (PKC) δ is a regulator of apoptosis with both pro- and anti-apoptotic effects. The mechanistic basis for the discrepant effects is not completely understood. Here we show that Smac interacts with PKCδ. The interaction depends on the N-terminus of Smac and is disrupted upon treatment with paclitaxel. This is associated with release of Smac into the cytosol. Activation of PKCδ rescues the interaction during paclitaxel exposure and suppresses the paclitaxel-mediated cell death. However, under these conditions the complex is mainly found in the cytosol suggesting that cytosolic Smac can be bound by PKCδ when PKC is activated. The data unravel a previously unrecognized interaction and suggest that PKCδ by associating with Smac may prevent its apoptotic effects.
authors.affiliation: Lund University, Center for Molecular Pathology, Skåne University Hospital, Malmö, Sweden.
authors.forename: Katarzyna Chmielarska
authors.initials: KC
authors.lastname: Masoumi
authors.forename: Louise
authors.initials: L
authors.lastname: Cornmark
authors.forename: Gry Kalstad
authors.initials: GK
authors.lastname: Lønne
authors.forename: Ulf
authors.initials: U
authors.lastname: Hellman
authors.forename: Christer
authors.initials: C
authors.lastname: Larsson
mesh_terms: D017209:Apoptosis; D003600:Cytosol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology*; D051745:Protein Kinase C-delta / Q000737:chemistry* / Q000378:metabolism
chemical_list: D009842:Oligopeptides; C532637:SMAC peptide; D051745:Protein Kinase C-delta; D017239:Paclitaxel