Walton M, Woodgate A M, Muravlev A, Xu R, During M J, Dragunow M
Department of Pharmacology, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
J Neurochem. 1999 Nov;73(5):1836-42.
The cyclic AMP-responsive element binding protein (CREB) is a posttranslationally activated transcription factor that has been implicated in numerous brain functions including cell survival. In this study we investigated whether CREB overexpression using transient transfection of a pAAV/CMV-CREB plasmid altered neuronal cells' susceptibility to apoptosis. We found that elevated CREB protein inhibited apoptosis induced by okadaic acid. At least part of this effect is critically dependent on prolonged Ser133 phosphorylation, as a directed mutation at this site decreased CREB-induced protection. These results suggest that CREB is a survival factor for neuronal cells and that treatments aimed at augmenting CREB phosphorylation in the brain may be neuroprotective.
环磷酸腺苷反应元件结合蛋白（CREB）是一种翻译后被激活的转录因子，它与包括细胞存活在内的多种脑功能有关。在本研究中，我们调查了通过瞬时转染pAAV/CMV-CREB质粒来过度表达CREB是否会改变神经元细胞对凋亡的易感性。我们发现，CREB蛋白水平升高可抑制冈田酸诱导的凋亡。这种效应至少部分严重依赖于Ser133位点的持续磷酸化，因为该位点的定向突变会降低CREB诱导的保护作用。这些结果表明，CREB是神经元细胞的存活因子，旨在增强大脑中CREB磷酸化的治疗可能具有神经保护作用。
