ArticleProceedings of the National Academy of Sciences of the United States of America2013
Dissection of TBK1 signaling via phosphoproteomics in lung cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 122 citations in OpenAlex.
- Endogenous inhibitors of PP2A activate oncogenic and DNA damage response kinases in glioblastoma.Cancer letters · 2026Article
- Selective degradation of TBK1 uncovers mechanistic insights into blocking ccRCC progression.Cell chemical biology · 2026Article
- Proteolytic profiling of human plasma reveals an immunoactive complement C3 fragment.The EMBO journal · 2025Article
- PHLDA2 in cancer: From molecular mechanisms to therapeutic opportunities.The Journal of pharmacology and experimental therapeutics · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Kinome profiling reveals pathogenic variant specific protein signalling networks in MEN2 children with Medullary Thyroid Cancer.NPJ precision oncology · 2025Article
- Basic biology and roles of CEBPD in cardiovascular disease.Cell death discovery · 2025Review
- TBK1 inhibitor amlexanox exerts anti-cancer effects against endometrial cancer by regulating AKT/NF-κB signaling.International journal of biological sciences · 2025Article
- Phosphorylation regulates the chromatin remodeler SMARCAD1 in nucleosome binding, ATP hydrolysis, and histone exchange.The Journal of biological chemistry · 2024Article
- Targeting TANK-binding kinase 1 attenuates painful diabetic neuropathy via inhibiting microglia pyroptosis.Cell communication and signaling : CCS · 2024Article
- CAMKV Kinase Signaling Is a Novel Therapeutic Avenue with Prognostic Relevance in Neuroblastoma.bioRxiv : the preprint server for biology · 2024Article
- NAK-associated protein 1/NAP1 activates TBK1 to ensure accurate mitosis and cytokinesis.The Journal of cell biology · 2024Article
- TBK1 is paradoxical in tumor development: a focus on the pathway mediating IFN-I expression.Frontiers in immunology · 2024Review
- The Role of cGAS-STING Signalling in Metabolic Diseases: from Signalling Networks to Targeted Intervention.International journal of biological sciences · 2024Review
- Role of TBK1 Inhibition in Targeted Therapy of Cancer.Mini reviews in medicinal chemistry · 2024Review
- Endothelial deletion of TBK1 contributes to BRB dysfunction via CXCR4 phosphorylation suppression.Cell death discovery · 2022Article
- The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target.Biomedicines · 2022Review
- Frustration analysis of TBK1 missense mutations reported in ALS/FTD and cancer patients.3 Biotech · 2022Article
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- E3 Ubiquitin Ligase Regulators of Notch Receptor Endocytosis: From Flies to Humans.Biomolecules · 2022Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
TANK-binding kinase 1 (TBK1) has emerged as a novel therapeutic target for unspecified subset of lung cancers. TBK1 reportedly mediates prosurvival signaling by activating NF-κB and AKT. However, we observed that TBK1 knockdown also decreased viability of cells expressing constitutively active NF-κB and interferon regulatory factor 3. Basal phospho-AKT level was not reduced after TBK1 knockdown in TBK1-sensitive lung cancer cells, implicating that TBK1 mediates unknown survival mechanisms. To gain better insight into TBK1 survival signaling, we searched for altered phosphoproteins using mass spectrometry following RNAi-mediated TBK1 knockdown. In total, we identified 2,080 phosphoproteins (4,621 peptides), of which 385 proteins (477 peptides) were affected after TBK1 knockdown. A view of the altered network identified a central role of Polo-like kinase 1 (PLK1) and known PLK1 targets. We found that TBK1 directly phosphorylated PLK1 in vitro. TBK1 phosphorylation was induced at mitosis, and loss of TBK1 impaired mitotic phosphorylation of PLK1 in TBK1-sensitive lung cancer cells. Furthermore, lung cancer cell sensitivity to TBK1 was highly correlated with sensitivity to pharmacological PLK inhibition. We additionally found that TBK1 knockdown decreased metadherin phosphorylation at Ser-568. Metadherin was associated with poor outcome in lung cancer, and loss of metadherin caused growth inhibition and apoptosis in TBK1-sensitive lung cancer cells. These results collectively revealed TBK1 as a mitosis regulator through activation of PLK1 and also suggested metadherin as a putative TBK1 downstream effector involved in lung cancer cell survival.
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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.