title: A novel mouse PKCδ splice variant, PKCδIX, inhibits etoposide-induced apoptosis.
abstract: Protein kinase C (PKC) δ plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKCδ generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKCδ isoform named PKCδIX (Genebank Accession No. HQ840432). PKCδIX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKCδ. PKCδIX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKCδIX provided a possibility that this PKCδ isozyme functions as a novel dominant-negative form for PKCδ due to its lack of the ATP-binding domain that is required for the kinase activity of PKCδ. Indeed, overexpression of PKCδIX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKCδIX protein could competitively inhibit the kinase activity of PKCδ. We conclude that PKCδIX can function as a natural dominant-negative inhibitor of PKCδin vivo.
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea.
authors.forename: Jung D
authors.initials: JD
authors.lastname: Kim
authors.forename: Kwang W
authors.initials: KW
authors.lastname: Seo
authors.forename: Eun A
authors.initials: EA
authors.lastname: Lee
authors.forename: Nguyen N
authors.initials: NN
authors.lastname: Quang
authors.forename: Hong R
authors.initials: HR
authors.lastname: Cho
authors.forename: Byungsuk
authors.initials: B
authors.lastname: Kwon
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites; D020134:Catalytic Domain; D002467:Cell Nucleus / Q000201:enzymology; D005047:Etoposide / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D019913:Nuclear Localization Signals; D005047:Etoposide; D000255:Adenosine Triphosphate; D051745:Protein Kinase C-delta