title: c-Jun expression, activation and function in neural cell death, inflammation and repair.
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 employing in vivo strategies 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 roles in vivo could considerably increase the potential of pharmacological agents to improve neurological outcome following trauma, neonatal encephalopathy and stroke, as well as in neurodegenerative disease.
authors.affiliation: Department of Obstetrics and Gynaecology, Perinatal Brain Repair Group, EGA Institute of Women's Health, London, UK. g.raivich@ucl.ac.uk
authors.forename: Gennadij
authors.initials: G
authors.lastname: Raivich
mesh_terms: D000818:Animals; D016923:Cell Death; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D012694:Serine; D013912:Threonine
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D013912:Threonine; D012694:Serine