[Role p53 and MAPK signaling integration in the regulation of PC12 cell neural differentiation]

p53 is a transcription factor and then induced by cellular stress regulates ageing, cell cycle arrest and apoptosis. Published data also demonstrated that p53 participates in the regulation of neuronal differentiation. However, the data concerning the mechanisms of neuronal differentiation by p53 is very limited. In the present work we have studied a role and mechanisms of p53 activated by Nutlin-3 in the differentiation of PC12 cells. In our experiments Nutlin-3 stimulated the cell differentiation by significantly increasing of the neuritis upgrowth and upregulation of tyrosine hydroxylase (TH) expression, the catecholamine main rate-limited ferment. We have also analyzed MAPK signaling cascade that tightly participate in the neuronal differentiation. Obtained data demonstrated that activation of p53 by Nutlin-3 injections increased the activity of cRaf and ERK1/2, as well as transcription factor CREB, which is one of the targets for ERK pathway and regulates transcription of TH. Thus, we demonstrated that p53 activation lead to increased differentiation of PC12 cells and this effect is mediated by cRaf/ERK/CREB pathway.