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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.

SUBMITTER: Marquez-Lona EM

PROVIDER: S-EPMC3259220 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other

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Nucleolar stress characterized by downregulation of nucleophosmin: a novel cause of neuronal degeneration.

Marquez-Lona Esther Magdalena EM Tan Zhiqun Z Schreiber Steven S SS

Biochemical and biophysical research communications 20111207 1

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 excitotoxic ...[more]

PMID: 22166220

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