CAMP-responsive element

Biosynthesis. CRE is derived from a precursor of 196 amino acids (84,85). This gene contains one copy of CRE, which is flanked by double basic amino acids. The amino acid sequence of the CRE precursor suggests that it may arise from proteins related to POMC and neurophysins (31). The CRE precursor contains a cAMP responsive element which aHows stimulation of mRNA synthesis when intraceHular levels of cAMP are increased (86). 

The cAMP responsive element binding factor (CREB) is also activated by phosphorylation. Depending on the stimuli, CREB is the target of a cAMP dependent protein kinase or of kinases called MAPKs, RSK, and CamKIV. As in AP-1, CREB carries a basic leucine zipper motif (bZDP), which mediates homo dimerization of CREB when bound to the CRE. 

Shaw-Lutchman TZ, Barrot M, Wallace T, et al Regional and cellular mapping of cAMP response element-mediated transcription during naltrexone-precipitated morphine withdrawal. J Neurosci 22 3663-3672, 2002 Shreeram SS, McDonald T, Dennison S Psychosisafterultrarapidopiatedetoxification (letter). Am J Psychiatry 158 970, 2001... 

Adenovirus transcription factor (ATF) is a protein activated by the adenovirus protein E2a and has turned out to be CREB (cAMP-responsive, element-binding protein) Jun is named for avian sarcoma virus 17 (I am told that junana is 17 in Japanese). 

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. 

Thome J., Sakain N., Shin K. et al. (2000). cAMP response element-mediated gene transcription in upregulated by chronic antidepressant. J. Neurosci. 20, 4030-6. 

Newton, S.S., Thome, J., Wallace, T.L. et al. Inhibition of cAMP response element-binding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect. J. Neurosci. 22 10883, 2002. 

This list is not intended to be comprehensive but to indicate the wide array of neuronal proteins regulated by phosphorylation. Some of the proteins are specific to neurons but most are present in many cell types in addition to neurons and are included because their multiple functions in the nervous system include the regulation of neuron-specific phenomena. Not included are the many phosphoproteins present in diverse tissues, including brain, that play a role in generalized cellular processes, such as intermediary metabolism, and that do not appear to play a role in neuron-specific phenomena. NMDA, N-methyl-D-aspartate CREB, cAMP response element-binding proteins STAT, signal-transducing activators of transcription ... 

Cyclic AMP controls phosphorylation of the cAMP response element binding protein 466... 

The cAMP response element binding protein is a member of a family containing interacting proteins 467... 

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.)... 

Perazzona B, Isabel G, Preat T and Davis R. L. The role of cAMP response element-binding protein in Drosophila long-term memory. /. Neurosci. 24 8823-8828, 2004. 

Balschun, D., Wolfer D. P, Gass, P. etal. Does cAMP response element-binding protein have a pivotal role in hippocampal... 

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. 

CRE cAMP responsive element GABA y-aminobutyric acid... 

CBP CREB (cAMP-response element binding protein)-binding protein... 

---