Yeast ornithine decarboxylase and antizyme form a 1:1 complex in vitro: purification and characterization of the inhibitory complex |
| |
Authors: | Chattopadhyay Manas K Fernandez Cristina Sharma Deepak McPhie Peter Masison Daniel C |
| |
Institution: | aSchool of Biological Sciences, University of Ulsan, Ulsan, Republic of Korea;bDepartment of Internal Medicines, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan, Republic of Korea;cDepartment of Surgery, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan, Republic of Korea;dBiomedical Research Center, Ulsan University Hospital and School of Medicine, University of Ulsan, Ulsan, Republic of Korea |
| |
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 PKCδ in vivo. |
| |
Keywords: | Apoptosis Dominant-negative Etoposide Kinase activity PKCδ Splice variant |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|