title: WISP1 (CCN4) autoregulates its expression and nuclear trafficking of β-catenin during oxidant stress with limited effects upon neuronal autophagy.
abstract: Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4) is a CCN family member more broadly identified with development and tumorigenesis. However, recent studies have shed new light and enthusiasm on WISP1 as a novel target directed against toxic cell degeneration. Here we show WISP1 prevents apoptotic degeneration in primary neurons during oxidant stress through the activation of protein kinase B (Akt1), the post-translational maintenance of β-catenin integrity that is consistent with inhibition of glycogen synthase kinase-3β (GSK-3β), and the subcellular trafficking of β- catenin to foster its translocation to the nucleus. Interestingly, WISP1 autoregulates its expression through the promotion of β-catenin activity and may employ β-catenin to have a limited control over autophagy, but neuronal injury during oxidant stress as a result of autophagy appears portioned to a small population of neurons without significant impact upon overall cell survival. New strategies that target WISP1, its autoregulation, and the pathways responsible for neuronal cell injury may bring forth new insight for the treatment of neurodegenerative disorders.
authors.affiliation: Laboratory of Cellular and Molecular Signaling, Cancer Center, F 1220, New Jersey Health Sciences University, 205 South Orange Avenue, Newark, NJ 07101, USA.
authors.forename: Shaohui
authors.initials: S
authors.lastname: Wang
authors.forename: Zhao Zhong
authors.initials: ZZ
authors.lastname: Chong
authors.forename: Yan Chen
authors.initials: YC
authors.lastname: Shang
authors.forename: Kenneth
authors.initials: K
authors.lastname: Maiese
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D055511:CCN Intercellular Signaling Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006706:Homeostasis / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D016877:Oxidants / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D021381:Protein Transport / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D055511:CCN Intercellular Signaling Proteins; C492066:CCN4 protein, rat; C495268:Ctnnb1 protein, rat; D016877:Oxidants; D011518:Proto-Oncogene Proteins; D051176:beta Catenin