ArticleThe EMBO journal2002
Nuclear import of PKCdelta is required for apoptosis: identification of a novel nuclear import sequence.
Article in The EMBO journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed.
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Genome-wide profiling identifies the genetic dependencies of cell death following EGFR inhibition.The Journal of biological chemistry · 2026Article
- The C2 Domain of PKC‑δ as a Dominant-Negative Modulator of Breast Cancer Cell Survival and Chemosensitivity.ACS omega · 2025Article
- PKCδ Regulates DNA Damage and Cell Death through a SIRT6/Nrf2-dependent Antioxidant Response.Molecular cancer research : MCR · 2025Article
- Mitochondrial stress disassembles nuclear architecture through proteolytic activation of PKCδ and Lamin B1 phosphorylation in neuronal cells: implications for pathogenesis of age-related neurodegenerative diseases.Frontiers in cellular neuroscience · 2025Article
- Human NTHL1 expression and subcellular distribution determines cisplatin sensitivity in human lung epithelial and non-small cell lung cancer cells.NAR cancer · 2024Article
- PKCδ Regulates Chromatin Remodeling and DNA Repair through SIRT6.Molecular cancer research : MCR · 2024Article
- Into the fold: advances in understanding aPKC membrane dynamics.The Biochemical journal · 2023Article
- A Multimodel Study of the Role of Novel PKC Isoforms in the DNA Integrity Checkpoint.International journal of molecular sciences · 2023Article
- Dual Regulation of Spine-Specific and Synapse-to-Nucleus Signaling by PKCδ during Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Role of alternatively spliced, pro-survival Protein Kinase C delta VIII (PKCδVIII) in ovarian cancer.FASEB bioAdvances · 2022Article
- Article
- Multiple subcellular localizations and functions of protein kinase Cδ in liver cancer.World journal of gastroenterology · 2022Review
- When PIPFrontiers in cell and developmental biology · 2022Review
- Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Review
- Extracellular Histones Bind Vascular Glycosaminoglycans and Inhibit the Anti-Inflammatory Function of Antithrombin.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021Article
- Article
- Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions.Journal of clinical medicine · 2020Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
We have shown previously that protein kinase Cdelta (PKCdelta) is required for mitochondrial-dependent apoptosis. Here we show that PKCdelta is imported into the nucleus of etoposide-treated cells, that nuclear import is required for apoptosis and that it is mediated by a nuclear localization signal (NLS) in the C-terminus of PKCdelta. Mutation of the caspase cleavage site of PKCdelta inhibits nuclear accumulation in apoptotic cells, indicating that caspase cleavage facilitates this process. Expression of the PKCdelta catalytic fragment (CFdelta) in transfected cells results in nuclear localization and apoptosis. We show that the PKCdelta NLS is required for nuclear import of both full-length PKCdelta and CFdelta, and drives nuclear localization of a multimeric green fluorescent protein. Mutations within the NLS of CFdelta prevent nuclear accumulation and block apoptosis. Conversely, nuclear expression of a kinase-negative catalytic fragment (KN-CFdelta) protects cells from etoposide-induced apoptosis. Mutation of the NLS blocks the ability of KN-CFdelta to protect against etoposide-induced apoptosis. These results indicate that PKCdelta regulates an essential nuclear event(s) that is required for initiation of the apoptotic pathway.
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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.