ArticleMolecular and cellular biology1999
Protein kinase Cdelta targets mitochondria, alters mitochondrial membrane potential, and induces apoptosis in normal and neoplastic keratinocytes when overexpressed by an adenoviral vector.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 279 citations in OpenAlex.
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Mitochondrial Kinases and the Role of Mitochondrial Protein Phosphorylation in Health and Disease.Life (Basel, Switzerland) · 2021Review
- Article
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- Protein kinase C and cardiac dysfunction: a review.Heart failure reviews · 2017Review
- Dual action of NSC606985 on cell growth and apoptosis mediated through PKCδ in prostatic cancer cells.International journal of oncology · 2017Article
- HSV-1 ICP27 induces apoptosis by promoting Bax translocation to mitochondria through interacting with 14-3-3θ.BMB reports · 2017Article
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
- Regulation of mitochondrial functions by protein phosphorylation and dephosphorylation.Cell & bioscience · 2016Review
- Estrogen potentiates reactive oxygen species (ROS) tolerance to initiate carcinogenesis and promote cancer malignant transformation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- T cell PKCδ kinase inactivation induces lupus-like autoimmunity in mice.Clinical immunology (Orlando, Fla.) · 2015Article
- Protein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle.Journal of cellular and molecular medicine · 2015Article
- Stat3 binds to mtDNA and regulates mitochondrial gene expression in keratinocytes.The Journal of investigative dermatology · 2014Article
- Vitamin C suppresses cell death in MCF-7 human breast cancer cells induced by tamoxifen.Journal of cellular and molecular medicine · 2014Article
- S-nitrosation of mitochondrial connexin 43 regulates mitochondrial function.Basic research in cardiology · 2014Article
- Impaired translocation and activation of mitochondrial Akt1 mitigated mitochondrial oxidative phosphorylation Complex V activity in diabetic myocardium.Journal of molecular and cellular cardiology · 2013Article
- Isozyme-specific interaction of protein kinase Cδ with mitochondria dissected using live cell fluorescence imaging.The Journal of biological chemistry · 2012Article
- The essential role of protein kinase Cδ in diabetes-induced neural tube defects.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2012Article
- Cell signaling through protein kinase C oxidation and activation.International journal of molecular sciences · 2012Review
- Involvement of distinct PKC gene products in T cell functions.Frontiers in immunology · 2012Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Inactivation of protein kinase Cdelta (PKCdelta) is associated with resistance to terminal cell death in epidermal tumor cells, suggesting that activation of PKCdelta in normal epidermis may be a component of a cell death pathway. To test this hypothesis, we constructed an adenovirus vector carrying an epitope-tagged PKCdelta under a cytomegalovirus promoter to overexpress PKCdelta in normal and neoplastic keratinocytes. While PKCdelta overexpression was detected by immunoblotting in keratinocytes, the expression level of other PKC isozymes, including PKCalpha, PKCepsilon, PKCzeta, and PKCeta, did not change. Calcium-independent PKC-specific kinase activity increased after infection of keratinocytes with the PKCdelta adenovirus. Activation of PKCdelta by 12-O-tetradecanoylphorbol-13-acetate (TPA) at a nanomolar concentration was lethal to normal and neoplastic mouse and human keratinocytes overexpressing PKCdelta. Lethality was inhibited by PKC selective inhibitors, GF109203X and Ro-32-0432. TPA-induced cell death was apoptotic as evidenced by morphological criteria, TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay, DNA fragmentation, and increased caspase activity. Subcellular fractionation indicated that PKCdelta translocated to a mitochondrial enriched fraction after TPA activation, and this finding was confirmed by confocal microscopy of cells expressing a transfected PKCdelta-green fluorescent protein fusion protein. Furthermore, activation of PKCdelta in keratinocytes altered mitochondrial membrane potential, as indicated by rhodamine-123 fluorescence. Mitochondrial inhibitors, rotenone and antimycin A, reduced TPA-induced cell death in PKCdelta-overexpressing keratinocytes. These results indicate that PKCdelta can initiate a death pathway in keratinocytes that involves direct interaction with mitochondria and alterations of mitochondrial function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.