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 cel l populations in the brain, we have characterized Rel activation in as trocytes. A RelA homodimer is uniquely activated in cytokine-stimulate d astrocytes. Cytokine-dependent phosphorylation of the RelA inhibitor MAD-3 occurred on discrete peptides prior to its dissociation from Re lA. A transient hyperphosphorylation of RelA was also induced. Antioxi dant treatment inhibited both RelA activation and phosphorylation of t he RelA(.)MAD-3 complex, These results demonstrate that cytokine-depen dent activation of the RelA homodimer involves phosphorylation of both RelA and its associated inhibitor. The sole activation of a RelA homo dimer suggests that cytokines will activate a unique set of Rel-regula ted genes in astrocytes.