title: CD9 regulates transcription factor GCM1 and ERVWE1 expression through the cAMP/protein kinase A signaling pathway.
abstract: ERVWE1 (SYNCYTIN-1), a membrane protein originating from the envelope gene of human endogenous retrovirus-W (HERV-W), mediates the fusion of mononucleated cytotrophoblasts into multinucleated syncytiotrophoblast. Though ERVWE1 has been characterized since its discovery, regulatory mechanisms associated with ERVWE1 expression have not been firmly established. We hypothesized that membrane protein CD9, involved in cell-cell fusion of fertilization and myogenesis, could be involved in the regulation of ERVWE1 gene expression. In this study, regulatory mechanisms of ERVWE1 expression were studied using human choriocarcinoma BeWo cells. Forskolin is an activator of adenylate cyclase, which increased CD9 and ERVWE1 expression. The increase in CD9 expression was inhibited by a protein kinase A (PKA) inhibitor, Rp-cAMPS. These results indicate that CD9 expression is regulated by the cAMP/PKA signaling pathway. Overexpression of CD9 increased expression levels of ERVWE1 as well as GCM1 (hGCMa), which is a transcription factor known to activate ERVWE1 gene transcription. However, high ERVWE1 expression induced by CD9 overexpression did not result in the increase in chorionic gonadotropin, beta polypeptide production. Moreover, CD9-induced increase in ERVWE1 and GCM1 expressions were inhibited by Rp-cAMPS. These results suggest that CD9 increases GCM1 expression via the cAMP/PKA signaling pathway, resulting in the increase in ERVWE1 expression.
authors.affiliation: Laboratory of Animal Breeding, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-8657 Tokyo, Japan.
authors.forename: Yoshikage
authors.initials: Y
authors.lastname: Muroi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakurai
authors.forename: Akira
authors.initials: A
authors.lastname: Hanashi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kubota
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nagaoka
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Imakawa
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011257:Pregnancy Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D060245:Tetraspanin 29 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
chemical_list: C554869:CD9 protein, human; D004268:DNA-Binding Proteins; C491089:GCM1 protein, human; D015686:Gene Products, env; D009687:Nuclear Proteins; D011257:Pregnancy Proteins; D060245:Tetraspanin 29; D014157:Transcription Factors; C405335:syncytin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases