Tumor necrosis factor-alpha-dependent activation of a RelA homodimer in astrocytes. Increased phosphorylation of RelA and MAD-3 precede activation of RelA.
Rel proteins are important intracellular mediators of cytokine-induced signal transduction. To understand how cytokines affect different cell populations in the brain, we have characterized Rel activation in astrocytes. A RelA homodimer is uniquely activated in cytokine-stimulated astrocytes. Cytokine-dependent phosphorylation of the RelA inhibitor MAD-3 occurred on discrete peptides prior to its dissociation from RelA. A transient hyperphosphorylation of RelA was also induced. Antioxidant treatment inhibited both RelA activation and phosphorylation of the RelA.MAD-3 complex. These results demonstrate that cytokine-dependent activation of the RelA homodimer involves phosphorylation of both RelA and its associated inhibitor. The sole activation of a RelA homodimer suggests that cytokines will activate a unique set of Rel-regulated genes in astrocytes.
Biochemistry Department, University of Missouri, Columbia 65212.
J A
JA
Diehl
W
W
Tong
G
G
Sun
M
M
Hannink
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006868:Hydrolysis; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha