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Regulation of NF-κB RelA Phosphorylation and Transcriptional Activity by p21 and Protein Kinase Cζ in Primary Endothelial Cells
Open accessAbstract
The activity of the transcription factor NF-kappaB is thought to be regulated mainly through cytoplasmic retention by IkappaB molecules. Here we present evidence of a second mechanism of regulation acting on NF-kappaB after release from IkappaB. In endothelial cells this mechanism involves phosphorylation of the RelA subunit of NF-kappaB through a pathway involving activation of protein kinase Czeta (PKCzeta) and p21(ras). We show that transcriptional activity of RelA is dependent on phosphorylation of the N-terminal Rel homology domain but not the C-terminal transactivation domain. Inhibition of phosphorylation by dominant negative mutants of PKCzeta or p21(ras) results in loss of RelA transcriptional activity without interfering with DNA binding. Raf/MEK, small GTPases, phosphatidylinositol 3-kinase, and stress-activated protein kinase pathways are not involved in this mechanism of regulation.
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Cites
A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., & Karin, M. (1997) · Nature · doi:10.1038/41493 · Cited by 2,125
Cited by
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Missing Pieces in the NF-κB Puzzle
Ghosh, S., & Karin, M. (2002) · Cell · doi:10.1016/s0092-8674(02)00703-1 · Cited by 3,638
Tumor necrosis factor signaling
Wajant, H., Pfizenmaier, K., & Scheurich, P. (2003) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401189 · Cited by 2,359
LPS induction of gene expression in human monocytes
Guha, M., & Mackman, N. (2001) · Cellular Signalling · doi:10.1016/s0898-6568(00)00149-2 · Cited by 2,304
Mechanisms of Cell Protection by Heme Oxygenase-1
Gozzelino, R., Jeney, V., & Soares, M. P. (2010) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105600 · Cited by 1,241
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Metadata
- Authors
- Anrather, J., Csizmadia, V., Soares, M. P., & Winkler, H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 274
- Issue
- 19
- Pages
- 13594-13603
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2087047553
- Cited by
- 184
- References
- 1
- FWCI
- 7.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Regulation of NF-κB RelA Phosphorylation and Transcriptional Activity by p21 and Protein Kinase Cζ in Primary Endothelial Cells. https://app.cochat.ai/papers/10.1074/jbc.274.19.13594
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- Anrather, J., Csizmadia, V., Soares, M. P., & Winkler, H. (1999). Regulation of NF-κB RelA Phosphorylation and Transcriptional Activity by p21 and Protein Kinase Cζ in Primary Endothelial Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.19.13594
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
