Nucleolar stress characterized by downregulation of nucleophosmin: a novel cause of neuronal degeneration |
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Authors: | Marquez-Lona Esther Magdalena Tan Zhiqun Schreiber Steven S |
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Institution: | Department of Neurology, University of California, Irvine School of Medicine, Irvine, CA 92697-4275, United States. |
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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. |
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