ArticleThe Journal of biological chemistry2010
Phosphorylation of p50 NF-kappaB at a single serine residue by DNA-dependent protein kinase is critical for VCAM-1 expression upon TNF treatment.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 51 citations in OpenAlex.
- BNIP3L/BNIP3-Mediated Mitophagy Contributes to the Maintenance of Ovarian Cancer Stem Cells.Journal of cellular and molecular medicine · 2025Article
- Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: proteomics insights into Immunomodulation.Scientific reports · 2025Article
- Exosomal non-coding RNAs: key regulators of inflammation-related cardiovascular disorders.European journal of medical research · 2025Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- NFκB signalling in colorectal cancer: Examining the central dogma of IKKα and IKKβ signalling.Heliyon · 2024Review
- Unconventional activation of PRKDC by TNF-α: deciphering its crucial role in Th1-mediated inflammation beyond DNA repair as part of the DNA-PK complex.Journal of inflammation (London, England) · 2024Article
- DNA-dependent protein kinase catalytic subunit binds to the transactivation domain 1 of NF-κB p65.Biochemistry and biophysics reports · 2023Article
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- Ethanol extract ofPharmaceutical biology · 2021Article
- Proteome dynamics at broken replication forks reveal a distinct ATM-directed repair response suppressing DNA double-strand break ubiquitination.Molecular cell · 2021Article
- DNA-PK: gatekeeper for IKKγ/NEMO nucleocytoplasmic shuttling in genotoxic stress-induced NF-kappaB activation.Cellular and molecular life sciences : CMLS · 2020Article
- The regulation of sequence specific NF-κB DNA binding and transcription by IKKβ phosphorylation of NF-κB p50 at serine 80.Nucleic acids research · 2019Article
- Genome reading by the NF-κB transcription factors.Nucleic acids research · 2019Review
- Pleiotropic Impact of DNA-PK in Cancer and Implications for Therapeutic Strategies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Mechanistic link between DNA damage sensing, repairing and signaling factors and immune signaling.Advances in protein chemistry and structural biology · 2019Review
- The role of DNA-PK in aging and energy metabolism.The FEBS journal · 2018Review
- DNA damage, metabolism and aging in pro-inflammatory T cells: Rheumatoid arthritis as a model system.Experimental gerontology · 2018Review
- Long Non-Coding RNAs in Vascular Inflammation.Frontiers in cardiovascular medicine · 2018Article
- Engagement of Components of DNA-Break Repair Complex and NFκB in Hsp70A1A Transcription Upregulation by Heat Shock.PloS one · 2017Article
- Defects in the Fanconi Anemia Pathway in Head and Neck Cancer Cells Stimulate Tumor Cell Invasion through DNA-PK and Rac1 Signaling.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
The DNA binding activity of NF-κB is critical for VCAM-1 expression during inflammation. DNA-dependent protein kinase (DNA-PK) is thought to be involved in NF-κB activation. Here we show that DNA-PK is required for VCAM-1 expression in response to TNF. The phosphorylation and subsequent degradation of I-κBα as well as the serine 536 phosphorylation and nuclear translocation of p65 NF-κB were insufficient for VCAM-1 expression in response to TNF. The requirement for p50 NF-κB in TNF-induced VCAM-1 expression may be associated with its interaction with and phosphorylation by DNA-PK, which appears to be dominant over the requirement for p65 NF-κB activation. p50 NF-κB binding to its consensus sequence increased its susceptibility to phosphorylation by DNA-PK. Additionally, DNA-PK activity appeared to increase the association between p50/p50 and p50/p65 NF-κB dimers upon binding to DNA and after binding of p50 NF-κB to the VCAM-1 promoter. Analyses of the p50 NF-κB protein sequence revealed that both serine 20 and serine 227 at the amino terminus of the protein are putative sites for phosphorylation by DNA-PK. Mutation of serine 20 completely eliminated phosphorylation of p50 NF-κB by DNA-PK, suggesting that serine 20 is the only site in p50 NF-κB for phosphorylation by DNA-PK. Re-establishing wild-type p50 NF-κB, but not its serine 20/alanine mutant, in p50 NF-κB(-/-) fibroblasts reversed VCAM-1 expression after TNF treatment, demonstrating the importance of the serine 20 phosphorylation site in the induction of VCAM-1 expression. Together, these results elucidate a novel mechanism for the involvement of DNA-PK in the positive regulation of p50 NF-κB to drive VCAM-1 expression.
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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.