期刊论文详细信息
Biomolecules
Redox-Regulated Pathway of Tyrosine Phosphorylation Underlies NF-κB Induction by an Atypical Pathway Independent of the 26S Proteasome
Sarah Cullen2  Subramaniam Ponnappan1  Usha Ponnappan2 
[1] Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; E-Mail:;Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; E-Mail:
关键词: IκBα;    NF-κB;    proteasome;    phosphotyrosine;    pervanadate;    oxidative stress;    hypoxia/reoxygenation;   
DOI  :  10.3390/biom5010095
来源: mdpi
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【 摘 要 】

Alternative redox stimuli such as pervanadate or hypoxia/reoxygenation, induce transcription factor NF-κB by phospho-tyrosine-dependent and proteasome-independent mechanisms. While considerable attention has been paid to the absence of proteasomal regulation of tyrosine phosphorylated IκBα, there is a paucity of information regarding proteasomal regulation of signaling events distinct from tyrosine phosphorylation of IκBα. To delineate roles for the ubiquitin-proteasome pathway in the phospho-tyrosine dependent mechanism of NF-κB induction, we employed the proteasome inhibitor, Aclacinomycin, and the phosphotyrosine phosphatase inhibitor, pervanadate (PV). Results from these studies demonstrate that phospho-IκBα (Tyr-42) is not subject to proteasomal degradation in a murine stromal epithelial cell line, confirming results previously reported. Correspondingly, proteasome inhibition had no discernable effect on the key signaling intermediaries, Src and ERK1/2, involved in the phospho-tyrosine mechanisms regulating PV-mediated activation of NF-κB. Consistent with previous reports, a significant redox imbalance leading to the activation of tyrosine kinases, as occurs with pervanadate, is required for the induction of NF-κB. Strikingly, our studies demonstrate that proteasome inhibition can potentiate oxidative stress associated with PV-stimulation without impacting kinase activation, however, other cellular implications for this increase in intracellular oxidation remain to be fully delineated.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.

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