ArticleThe Journal of biological chemistry2013
Protein kinase A regulates MYC protein through transcriptional and post-translational mechanisms in a catalytic subunit isoform-specific manner.
Article in The Journal of biological chemistry, 2013. 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, 37 citations in OpenAlex.
- When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases.International journal of molecular sciences · 2023Review
- Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms.eLife · 2023Article
- A novel network pharmacology approach for leukaemia differentiation therapy using MogrifyOncogene · 2022Article
- Molecular Cross-Talk between Gravity- and Light-Sensing Mechanisms inInternational journal of molecular sciences · 2022Article
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- Application of cAMP-dependent catalytic subunit β (PRKACB) Low Expression in Predicting Worse Overall Survival: A Potential Therapeutic Target for Colorectal Carcinoma.Journal of Cancer · 2020Article
- Zinc Oxide nanoparticles induce oxidative and proteotoxic stress in ovarian cancer cells and trigger apoptosis Independent of p53-mutation status.Applied surface science · 2019Article
- miR-17-92 and miR-106b-25 clusters regulate beta cell mitotic checkpoint and insulin secretion in mice.Diabetologia · 2019Article
- The role of aurora A and polo-like kinases in high-risk lymphomas.Blood advances · 2019Review
- PLK1 Inhibition Targets Myc-Activated Malignant Glioma Cells Irrespective of Mismatch Repair Deficiency-Mediated Acquired Resistance to Temozolomide.Molecular cancer therapeutics · 2018Article
- Activating PRKACB somatic mutation in cortisol-producing adenomas.JCI insight · 2018Article
- USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer cells.Nature communications · 2018Article
- The Emerging Role of Polo-Like Kinase 1 in Epithelial-Mesenchymal Transition and Tumor Metastasis.Cancers · 2017Review
- An in vivo screening system to identify tumorigenic genes.Oncogene · 2017Article
- Quantifying Kinase-Specific Phosphorylation Stoichiometry Using Stable Isotope Labeling In a Reverse In-Gel Kinase Assay.Analytical chemistry · 2016Article
- Fasting and Systemic Insulin Signaling Regulate Phosphorylation of Brain Proteins That Modulate Cell Morphology and Link to Neurological Disorders.The Journal of biological chemistry · 2015Article
- DNAJB1-PRKACA is specific for fibrolamellar carcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015Article
- Cross-talk between PKA-Cβ and p65 mediates synergistic induction of PDE4B by roflumilast and NTHi.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Large-scale label-free comparative proteomics analysis of polo-like kinase 1 inhibition via the small-molecule inhibitor BI 6727 (Volasertib) in BRAF(V600E) mutant melanoma cells.Journal of proteome research · 2014Article
- β-Adrenergic Receptor Signaling in Prostate Cancer.Frontiers in oncology · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
MYC levels are tightly regulated in cells, and deregulation is associated with many cancers. In this report, we describe the existence of a MYC-protein kinase A (PKA)-polo-like kinase 1 (PLK1) signaling loop in cells. We report that sequential MYC phosphorylation by PKA and PLK1 protects MYC from proteasome-mediated degradation. Interestingly, short term pan-PKA inhibition diminishes MYC level, whereas prolonged PKA catalytic subunit α (PKACα) knockdown, but not PKA catalytic subunit β (PKACβ) knockdown, increases MYC. We show that the short term effect of pan-PKA inhibition on MYC is post-translational and the PKACα-specific long term effect on MYC is transcriptional. These data also reveal distinct functional roles among PKA catalytic isoforms in MYC regulation. We attribute this effect to differential phosphorylation selectivity among PKA catalytic subunits, which we demonstrate for multiple substrates. Further, we also show that MYC up-regulates PKACβ, transcriptionally forming a proximate positive feedback loop. These results establish PKA as a regulator of MYC and highlight the distinct biological roles of the different PKA catalytic subunits.
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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.