CREB phosphorylation promotes nerve cell survival

The cyclic AMP-responsive element binding protein (CREB) is a posttranslati onally activated transcription factor that has been implicated in numerous brain functions including cell survival. In this study we investigated whet her CREB overexpression using transient transfection of a pAAV/CMV-CREB pla smid altered neuronal cells' susceptibility to apoptosis. We found that ele vated CREB protein inhibited apoptosis induced by okadaic acid. At least pa rt: of this effect is critically dependent on prolonged Ser(133) phosphoryl ation, as a directed mutation at this site decreased CREB-induced protectio n. These results suggest that CREB is a survival factor for neuronal cells and that treatments aimed at augmenting CREB phosphorylation in the brain m ay be neuroprotective.