The cyclic AMP response element in the Bcl-2 promoter confers inducibilityby hypoxia in neuronal cells

In neuronal cells, expression of the anti-apoptotic Bcl-2 gene is induced b y hypoxia and produces a protective effect. We show here that this effect i s dependent upon the cyclic AMP response element (CRE) in the Bcl-2 promote r since mutation of this element abolishes the response and the isolated CR E can confer the response on a heterologous promoter. Interestingly however , the CRE in the Bcl-2 promoter does not render the promoter responsive to cyclic AMP and is not essential for its response to nerve growth factor. De spite the lack of cyclic AMP responsiveness, activation of the Bcl-2 promot er via the CRE in response to hypoxia requires the CREB transcription facto r and is associated with the enhanced phosphorylation of CREB on serine 133 and enhanced transcriptional activation by the CREB-binding protein, CBP, in response to hypoxia. This finding establishes the importance of the CRE in the induction of Bcl-2 gene expression by hypoxia, allowing the Bcl-2 pr otein to protect neuronal cells against this damaging stimulus. (C) 2001 El sevier Science BY All rights reserved.