Cyclic AMP response element—binding

Cyclic-AMP Response Element Binding Protein Cyclic GMP-dependent Protein Kinase Cyclic GMP-regulated Phosphodiesterases Cyclic Guanosine Monophosphate (Cyclic GMP cGMP)... 

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

CREB cyclic AMP response element binding protein... 

Pandey, S.C. The gene transcription factor cyclic AMP-responsive element binding protein role in positive and negative affective states of alcohol addiction. Pharmacol. Ther. 104 47, 2004. 

Habener, J. Cyclic AMP response element binding proteins A cornucopia of transcription factors. Mol. Endocrinol. 4 1087-1094,1990. 

FIGURE 35-6 Examples of apoptotic and antiapoptotic mechanisms that act on or within different subcellular compartments. CBP, Ca2+ binding protein CREB, cyclic AMP response element binding protein HSP, heat shock protein IP3, inositol 1,4,5-trisphosphate ROS, reactive oxygen species. 

An example of specific transcriptional control is cyclic AMP-dependent regulation of genes that have a cyclic AMP response element (CRE) through the action of the transcription factor CREB (cyclic AMP response element binding protein. Figure 12-5). 

BNST, bed nucleus of the stria terminalis CREB, cyclic AMP response element-binding protein CRH, corticotrophin-releasing hormone CS, conditioned stimuH GABA, y-aminobutyric acid GCC, voltage-gated calcium channels NE, norepinephrine NMDA, iST-methyl-D-aspartate PAG, periaqueductal gray. 

OgitaK. and Yoneda Y. (1994). Selective potentiation of DNA binding activities of both activator protein 1 and cyclic AMP response element binding protein through in vivo activation of N-methyl-D-aspartate receptor complex in mouse brain. J. Neurochem. 63 525-534. 

Emami KH, Nguyen C, Ma H, Kim DH, Jeong KW, Eguchi M, Moon RT, Teo JL, Oh SW, Kim HY, Moon SH, Ha JR, Kahn M. A small molecule inhibitor of beta-catenin/cyclic AMP response element-binding protein transcription. Proc. Natl. Acad. Sci. 2004 101 12682-12687. 

Nair A, Vaidya VA. Cyclic AMP response element binding protein and brain-derived neurotrophic factor molecules that modulate our mood J. Biosci. 2007 31 423-434. 

Figure 31.24. Coactivator Structure. The pi60 family of coactivators includes a number of domains that can be recognized at the amino acid sequence level, including a basic helix-loop-helix domain that takes part in DNA binding, a PAS domain that participates in protein-protein interactions, a central domain that contacts the ligandbinding domain of the nuclear hormone receptors, and a domain that interacts with additional coactivators such as p300 and CREB-binding protein (CBP). (CREB stands for cyclic AMP-response element binding protein.) The nuclear hormone receptor interaction domain includes three Leu-X-X-Leu-Leu sequences.

Figure 31.31. Cyclic AMP-Response Element Binding Protein (CREB). Each of two CREB subunits contributes a long a helix. The two helices coil around each other to form a dimeric DNA-binding unit. CREB is phosphorylated on a specific serine residue by protein kinase A.

But how do changes in monoamine transmitter levels produce an eventual elevation of mood Raised neurotransmitter concentrations produce immediate alterations in postsynaptic receptor activation, leading to changes in second messenger (intracellular) systems and to gradual modifications in cellular protein expression. Antidepressants increase a cyclic AMP response-element binding (CREB) protein which in turn is involved in... 

---