Synergy of activin and ciliary neurotrophic factor signaling pathways in the induction of vasoactive intestinal peptide gene expression

Autor: Jill Conover, R. Lee Pitts, James N. Coulombe, Ksenija Kos, Aviva J. Symes
Rok vydání: 2000
Předmět:
animal structures
Recombinant Fusion Proteins
Vasoactive intestinal peptide
Ciliary neurotrophic factor
Regulatory Sequences
Nucleic Acid
Transfection
Neuroblastoma
Endocrinology
Transforming Growth Factor beta
Gene expression
Tumor Cells
Cultured
Animals
Humans
Inhibins
Ciliary Neurotrophic Factor
Promoter Regions
Genetic
Molecular Biology
Activin type 2 receptors
Neuropeptide Gene
Binding Sites
biology
Drug Synergism
General Medicine
Activins
Neoplasm Proteins
DNA-Binding Proteins
Transcription Factor AP-1
STAT1 Transcription Factor
Gene Expression Regulation
embryonic structures
Mutation
biology.protein
Cancer research
Trans-Activators
Signal transduction
Chickens
hormones
hormone substitutes
and hormone antagonists
ACVR2B
Transforming growth factor
Signal Transduction
Vasoactive Intestinal Peptide
Zdroj: Molecular endocrinology (Baltimore, Md.). 14(3)
ISSN: 0888-8809
Popis: Activin, a member of the transforming growth factor-beta superfamily, can regulate neuropeptide gene expression in the nervous system and in neuroblastoma cells. Among the neuropeptide genes whose expression can be regulated by activin is the gene encoding the neuropeptide vasoactive intestinal peptide (VIP). To investigate the molecular mechanisms by which activin regulates neuronal gene expression, we have examined activin's regulation of VIP gene expression in NBFL neuroblastoma cells. We report here that NBFL cells respond to activin by increasing expression of VIP mRNA. Activin regulates VIP gene transcription in NBFL cells through a 180-bp element in the VIP promoter that was previously characterized to be necessary and sufficient to mediate the induction of VIP by the neuropoietic cytokines and termed the cytokine response element (CyRE). We find that the VIP CyRE is necessary and sufficient to mediate the transcriptional response to activin. In addition, ciliary neurotrophic factor (CNTF), a neuropoietic cytokine, synergizes with activin to increase VIP mRNA expression and transcription through the VIP CyRE. Mutations in either the Stat (signal transducer and activator of transcription) or AP-1 sites within the CyRE that reduce the response to CNTF, also reduce the response to activin. However, mutating both the Stat and AP-1 sites within the wild-type CyRE, while reducing the separate responses to either activin or CNTF, eliminates the synergy between them. These data suggest that activin and CNTF, two factors that appear to signal though distinct pathways, activate VIP gene transcription through a common transcriptional element, the VIP CyRE.
Databáze: OpenAIRE
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