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In this study, the effects of UPS dysfunction on cell cycle events in neuronal differentiated PC12 cells were analysed using a specific inhibitor of proteasome, lactacystin. Lactacystin induced apoptosis, G<jats:sub>2<\/jats:sub>\/M cell cycle arrest and sustained the phosphorylation of the pRB (retinoblastoma protein), the key molecular process of G<jats:sub>1<\/jats:sub>\/S transition, in neuronal PC12 cells. Furthermore, inhibition of cell cycle progression protected against lactacystin\u2010induced cell apoptosis. Finally, we determined that lactacystin activated the ERK signalling pathway. Inhibition of ERK1\/2 activation by MEK\u20101 inhibitor PD98059 decreased cell cycle aberrant and prevented apoptosis induced by lactacystin. These results indicate that aberrant cell cycle events contribute to apoptotic death induced by UPS dysfunction.<\/jats:p>","DOI":"10.1042\/cbi20090079","type":"journal-article","created":{"date-parts":[[2010,7,28]],"date-time":"2010-07-28T09:19:17Z","timestamp":1280308757000},"page":"1181-1187","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cell cycle events mediate lactacystin\u2010induced apoptotic death of neuronal PC12 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