CAMP responsive element binding protein CREB

Nibuya M., Nestlr E. J., Duman R. S. (1996). Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J. Neurosci. 16, 2365-72. 

FIGURE 26-8 Immunohistochemical localization of cAMP response element-binding protein (CREB) in rat hippocampal neurons. Using a polyclonal antibody which recognizes both CREB and phospho-CREB protein, it is apparent that CREB protein is enriched in the nucleus of pyramidal cells of the CA1 region of the hippocampus. Scale bar is 30 pm. (Courtesy of Dr Stephen Ginsberg, Department of Pathology, University of Pennsylvania.)... 

Antidepressant treatment has, in recent studies, been shown to upregulate the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) cascade and expression of BDNF [59]. This upregulation of CREB and BDNF raises the possibility that antidepressant treatment could oppose the cell death pathway, possibly via increased expression of the oncogene Bcl-2. Studies are necessary to determine if antidepressant treatment increases Bcl-2 expression. Increased expression of Bcl-2 in brain and cultured cells, and inhibition of apoptosis of cultured cerebellar granule neurons have been reported with lithium treatment [57]. Mice lacking the BDNF TrkB receptor fail to show behavioral and neurogenic responses to antidepressants. 

Lu Q, Hutchins AE, Doyle CM, Lundblad JR, Kwok RP (2003) Acetylation of CAMP-responsive element-binding protein (CREB) by CREB-binding protein enhances (REB-dependent Transcription. J Biol Chem. 278(18) 15727-15734... 

Chen A-H, Shirayama Y, Shin K-H, Neve RL, Duman RS (2001a) Expression of the cAMP response element binding protein (CREB) in hippocampus produces antidepressant effect. Biol Psychiatry 49 753-762... 

Lee B., Butcher G. Q., Hoyt K. R., Impey S., and Obrietan K. (2005a). Activity-dependent neuroprotection and cAMP response element-binding protein (CREB) kinase coupling, stimulus intensity, and temporal regulation of CREB phosphorylation at serine 133. J. Neurosci. 25 1137-1148. 

Stimulation of (3-ARs leads to activation of Gs protein, resulting in a subsequent increase in cAMP. This increase in cAMP induces stimulation of PKA and phosphorylation of the transcription factor cAMP responsive element binding protein (CREB). After this phosphorylation, CREB binds to the cAMP-responsive element in the promoter of many genes (Tan et al., 2007). 

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