ArticleThe Journal of biological chemistry2006
The protein kinase C delta catalytic fragment targets Mcl-1 for degradation to trigger apoptosis.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 55 citations in OpenAlex.
- 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
- A specific small-molecule inhibitor of protein kinase CδI activity improves metabolic dysfunction in human adipocytes from obese individuals.The Journal of biological chemistry · 2019Article
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
- Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in neurons.Cell death and differentiation · 2013Article
- Article
- Deletion of protein kinase Cδ in mice modulates stability of inflammatory genes and protects against cytokine-stimulated beta cell death in vitro and in vivo.Diabetologia · 2011Article
- A molecular signature of proteinuria in glomerulonephritis.PloS one · 2010Article
- Vitamin A metabolite, all-trans-retinoic acid, mediates alternative splicing of protein kinase C deltaVIII (PKCdeltaVIII) isoform via splicing factor SC35.The Journal of biological chemistry · 2010Article
- PKC-delta and -eta, MEKK-1, MEK-6, MEK-3, and p38-delta are essential mediators of the response of normal human epidermal keratinocytes to differentiating agents.The Journal of investigative dermatology · 2010Article
- Loss of protein kinase C delta gene expression in human squamous cell carcinomas: a laser capture microdissection study.The American journal of pathology · 2010Article
- Role of calpain-9 and PKC-delta in the apoptotic mechanism of lumen formation in CEACAM1 transfected breast epithelial cells.Experimental cell research · 2010Article
- The protein kinase Cdelta catalytic fragment is critical for maintenance of the G2/M DNA damage checkpoint.The Journal of biological chemistry · 2010Article
- Role for PKC δ in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells.Journal of signal transduction · 2010Article
- Caspases and kinases in a death grip.Cell · 2009Review
- Protein kinase Cdelta stimulates proteasome-dependent degradation of C/EBPalpha during apoptosis induction of leukemic cells.PloS one · 2009Article
- Cracking the BAFF code.Nature reviews. Immunology · 2009Review
- Mcl-1 functions as major epidermal survival protein required for proper keratinocyte differentiation.The Journal of investigative dermatology · 2009Article
- Protein kinase C isoforms: Multi-functional regulators of cell life and death.Frontiers in bioscience (Landmark edition) · 2009Review
- Novel roles for protein kinase Cdelta-dependent signaling pathways in acute hypoxic stress-induced autophagy.The Journal of biological chemistry · 2008Article
- Akt-mediated eminent expression of c-FLIP and Mcl-1 confers acquired resistance to TRAIL-induced cytotoxicity to lung cancer cells.Molecular cancer therapeutics · 2008Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Proteolytic cleavage and subsequent activation of protein kinase C (PKC) delta is required for apoptosis induced by a variety of genotoxic agent, including UV radiation. In addition, overexpression of the constitutively active PKCdelta catalytic fragment (PKCdelta-cat) is sufficient to trigger Bax activation, cytochrome c release, and apoptosis. While PKCdelta is a key apoptotic effector, the downstream target(s) responsible for the mitochondrial apoptotic cascade are not known. We found that expression of the active PKCdelta-cat in HaCaT cells triggers a reduction in the anti-apoptotic protein Mcl-1, similar to UV radiation. The down-regulation of Mcl-1 induced by PKCdelta-cat was not at the mRNA level but was due to decreased protein half-life. Overexpression of Mcl-1 protected HaCaT cells from both UV and PKCdelta-cat-induced apoptosis and blocked the release of cytochrome c from the mitochondria, indicating that Mcl-1 down-regulation was required for apoptosis signaling. Indeed, down-regulation of Mcl-1 with siRNA slightly increased the basal apoptotic rate of HaCaT cells and dramatically sensitized them to UV or PKCdelta-cat-induced apoptosis. HaCaT cells with down-regulated Mcl-1 had higher activated Bax protein, as measured by Bax cross-linking, indicating that Mcl-1 down-regulation is sufficient for Bax activation. Finally, recombinant PKCdelta could phosphorylate Mcl-1 in vitro, identifying Mcl-1 as a direct target for PKCdelta. Overall our results identify Mcl-1 as an important target for PKCdelta-cat that can mediate its pro-apoptotic effects on mitochondria to amplify the apoptotic signaling induced by a wide range of apoptotic stimuli.
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Registered trials
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.