Pituitary adenylate cyclase-activating polypeptide (PACAP) targets Down syndrome candidate region 1 (DSCR1/RCAN1) to control neuronal differentiation [Cell Biology]

July 8th, 2015 by Lee, E. H., Kim, S. S., Lee, S., Baek, K.-H., Seo, S. R.

The pituitary adenylate cyclase-activating peptide (PACAP) is a neurotrophic peptide involved in a wide range of nervous system functions, including development, differentiation, survival, and various aspects of learning and memory. Here, we report that PACAP induces the expression of the regulator of calcineurin 1 (RCAN1, also known as DSCR1), which is abnormally expressed in the brains of Down syndrome (DS) patients. Increased RCAN1 expression is accompanied by activation of the PKA-CREB pathways. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis demonstrate the presence of a functional cAMP response element (CRE) 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 for RCAN1, a DS-related gene, as a novel target for the control of neurotrophic function of PACAP.
  • Posted in Journal of Biological Chemistry, Publications
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