Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of Regulator of Calcineurin 1 (RCAN1/DSCR1/Adapt78) is known to inhibit the calcineurin-NFAT dependent signaling pathway. In this report, we find that activation of adenylate cyclase by forskolin increases the expression of RCAN1 through the increase of the protein's half-life. The ability of forskolin to increase the accumulation of RCAN1 protein is significantly inhibited with protein kinase A inhibitors such as KT5720 and H-89. Furthermore, forskolin targets the central and C-terminal region of RCAN1 and enhances the inhibitory effect of RCAN1 on the calcineurin-mediated activation of NFAT. Our findings provide the first evidence that the accumulation of the RCAN1 protein by cAMP acts as an important regulatory mechanism in the control of the calcineurin-dependent cellular pathway.
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PMID:Activation of adenylate cyclase by forskolin increases the protein stability of RCAN1 (DSCR1 or Adapt78). 1975 21

Pituitary adenylate cyclase-activating peptide (PACAP) is a neurotrophic peptide involved in a wide range of nervous functions, including development, differentiation, and survival, and various aspects of learning and memory. Here we report that PACAP induces the expression of regulator of calcineurin 1 (RCAN1, also known as DSCR1), which is abnormally expressed in the brains of Down syndrome patients. Increased RCAN1 expression is accompanied by activation of the PKA-cAMP response element-binding protein pathways. EMSA and ChIP analyses demonstrate the presence of a functional cAMP response element in the RCAN1 promoter. Moreover, we show that PACAP-dependent neuronal differentiation is significantly disturbed by improper RCAN1 expression. Our data provide the first evidence of RCAN1, a Down syndrome-related gene, as a novel target for control of the neurotrophic function of PACAP.
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PMID:Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation. 2615 40