Elucidating the role of nucleolus in neuronal cell death pathways: Assessing the neuroprotective role of Nucleophosmin protein (NPM).

摘要

Nucleophosmin (NPM) is a regulatory protein that is located in the nucleolus and has a widespread role in modulating cell cycle progression. In non-neuronal cell lines, NPM has been linked to the regulation of the tumor suppressor protein p53, by both enhancing and inhibiting its activity. Although the exact mechanisms for this diametrically opposite regulation are not known, transcriptional activation of p53 by NPM, along with a parallel increase in cytoplasmic NPM levels, have been shown to trigger cell death. Whether NPM also interacts with p53 in neuronal models, possess a substantial role in cell cycle regulation or can provide protective effects to damage cells remains elusive. Here, we assessed the neuroprotective role of NPM in neurodegenerative models by its over expression and down regulation using seizure-induced model. We show by molecular biology techniques that NPM over expression suggests a neuroprotective effect after kainic acid induced cellular insult, and that the down-regulation of NPM is pro-apoptotic in a p53-independent manner. These results indicate a key role for NPM in neuronal survival mechanisms.