title: Nucleolar stress characterized by downregulation of nucleophosmin: a novel cause of neuronal degeneration.
abstract: Nucleophosmin (NPM) is a multifunctional nucleolar protein that has been linked with nucleolar stress. In non-neuronal cell lines, NPM may enhance or inhibit the activity of tumor suppressor p53, a major apoptotic protein. The relationship between NPM and p53 in the central nervous system (CNS) remains unknown. Here, we assessed the role of NPM in the CNS using a model of seizure-induced neurodegeneration. We show that NPM overexpression is neuroprotective against kainic acid-induced excitotoxicity, and that downregulation of NPM is pro-apoptotic in a p53-independent manner. These results suggest a key role for NPM in promoting neuronal survival and a novel mechanism of neuronal degeneration triggered by nucleolar stress.
authors.affiliation: Department of Neurology, University of California, Irvine School of Medicine, Irvine, CA 92697-4275, United States.
authors.forename: Esther Magdalena
authors.initials: EM
authors.lastname: Marquez-Lona
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Tan
authors.forename: Steven S
authors.initials: SS
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism*; D002470:Cell Survival; D015536:Down-Regulation; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin