title: Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation.
abstract: 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.
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea and.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea and.
authors.forename: Seon Sook
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Molecular and Cellular Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746, Republic of Korea.
authors.forename: Seul
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746, Republic of Korea.
authors.forename: Kwan-Hyuck
authors.initials: KH
authors.lastname: Baek
authors.affiliation: Department of Molecular Bioscience, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea and. Electronic address: suryeonseo@kangwon.ac.kr.
authors.forename: Su Ryeon
authors.initials: SR
authors.lastname: Seo
mesh_terms: D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D011485:Protein Binding; D051381:Rats; D020218:Response Elements; D015398:Signal Transduction
chemical_list: C495402:Adcyap1 protein, mouse; D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D008156:Luciferases
keywords: DSCR1; PACAP; PKA; RCAN1; cAMP response element-binding protein (CREB); differentiation; neuron; neuropeptide