ArticleThe Journal of biological chemistry2011
Regulated binding of importin-α to protein kinase Cδ in response to apoptotic signals facilitates nuclear import.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Protein Kinase C-delta (PKCδ) in Neurodegeneration and Cerebral Ischemia: Molecular Mechanisms and Therapeutic Implications.Cell biochemistry and biophysics · 2026Review
- Modelling the Full-Length Inactive PKC-δ Structure to Explore Regulatory Accessibility and Selective Targeting Opportunities.Pharmaceuticals (Basel, Switzerland) · 2025Article
- PKCδ Regulates DNA Damage and Cell Death through a SIRT6/Nrf2-dependent Antioxidant Response.Molecular cancer research : MCR · 2025Article
- PKCδ Regulates Chromatin Remodeling and DNA Repair through SIRT6.Molecular cancer research : MCR · 2024Article
- An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- A Multimodel Study of the Role of Novel PKC Isoforms in the DNA Integrity Checkpoint.International journal of molecular sciences · 2023Article
- Extended-synaptotagmin 1 engages in unconventional protein secretion mediated via SEC22BProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Extracellular PKCδ signals to epidermal growth factor receptor for tumor proliferation in liver cancer cells.Cancer science · 2022Article
- Polyglutamine Expansion in Huntingtin and Mechanism of DNA Damage Repair Defects in Huntington's Disease.Frontiers in cellular neuroscience · 2022Review
- Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Review
- 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
- 12-Deoxyphorbol Esters Induce Growth Arrest and Apoptosis in Human Lung Cancer A549 Cells Via Activation of PKC-δ/PKD/ERK Signaling Pathway.International journal of molecular sciences · 2020Article
- Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy.Cancers · 2019Review
- EGF receptor and PKCδ kinase activate DNA damage-induced pro-survival and pro-apoptotic signaling via biphasic activation of ERK and MSK1 kinases.The Journal of biological chemistry · 2019Article
- Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease.Biochemical pharmacology · 2018Review
- Tyrosine Kinase Inhibitors Protect the Salivary Gland from Radiation Damage by Inhibiting Activation of Protein Kinase C-δ.Molecular cancer therapeutics · 2017Article
- Co-dependency of PKCδ and K-Ras: inverse association with cytotoxic drug sensitivity in KRAS mutant lung cancer.Oncogene · 2017Article
- Protein Kinase C as Regulator of Vascular Smooth Muscle Function and Potential Target in Vascular Disorders.Advances in pharmacology (San Diego, Calif.) · 2017Review
- Multifunctional roles of PKCδ: Opportunities for targeted therapy in human disease.Pharmacology & therapeutics · 2016Review
- Molecular characterization of protein kinase C delta (PKCδ)-Smac interactions.BMC biochemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
PKCδ translocates into the nucleus in response to apoptotic agents and functions as a potent cell death signal. Cytoplasmic retention of PKCδ and its transport into the nucleus are essential for cell homeostasis, but how these processes are regulated is poorly understood. We show that PKCδ resides in the cytoplasm in a conformation that precludes binding of importin-α. A structural model of PKCδ in the inactive state suggests that the nuclear localization sequence (NLS) is prevented from binding to importin-α through intramolecular contacts between the C2 and catalytic domains. We have previously shown that PKCδ is phosphorylated on specific tyrosine residues in response to apoptotic agents. Here, we show that phosphorylation of PKCδ at Tyr-64 and Tyr-155 results in a conformational change that allows exposure of the NLS and binding of importin-α. In addition, Hsp90 binds to PKCδ with similar kinetics as importin-α and is required for the interaction of importin-α with the NLS. Finally, we elucidate a role for a conserved PPxxP motif, which overlaps the NLS, in nuclear exclusion of PKCδ. Mutagenesis of the conserved prolines to alanines enhanced importin-α binding to PKCδ and induced its nuclear import in resting cells. Thus, the PPxxP motif is important for maintaining a conformation that facilitates cytosplasmic retention of PKCδ. Taken together, this study establishes a novel mechanism that retains PKCδ in the cytoplasm of resting cells and regulates its nuclear import in response to apoptotic stimuli.
Indexed as
Identifiers
What OpenQuestion holds
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.