c‐Jun Expression, activation and function in neural cell death, inflammation and repair

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Abstract
Up‐regulation of c‐Jun is a common event in the developing, adult as well as in injured nervous system that serves as a model of transcriptional control of brain function. Functional studies employingin vivostrategies using gene deletion, targeted expression of dominant negative isoforms and pharmacological inhibitors all suggest a three pronged role of c‐Jun action, exercising control over neural cell death and degeneration, in gliosis and inflammation as well as in plasticity and repair.In vitro, structural and molecular studies reveal several non‐overlapping activation cascades via N‐terminal c‐Jun phosphorylation at serine 63 and 73 (Ser63, Ser73), and threonine 91 and 93 (Thr91, Thr93) residues, the dephosphorylation at Thr239, the p300‐mediated lysine acetylation of the near C‐terminal region (Lys268, Lys271, Lys 273), as well as the Jun‐independent activities of the Jun N‐terminal family of serine/threonine kinases, that regulate the different and disparate cellular responses. A better understanding of these non‐overlapping rolesin vivocould considerably increase the potential of pharmacological agents to improve neurological outcome following trauma, neonatal encephalopathy and stroke, as well as in neurodegenerative disease.