title: PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation.
abstract: Glial cells missing Drosophila homolog a (GCMa) is a member of the GCM transcription factor family and plays critical roles in trophoblast differentiation and placental functions. It is well established that the cyclic AMP (cAMP)-dependent pathway induces the expression and transcriptional activity of GCMa by regulating post-translational modifications of GCMa, which results in enhancement of trophoblast differentiation. We previously observed that phorbol 12-myristate 13-acetate (PMA) stimulates phosphorylation of GCMa on serines 328, 378 and 383 through the protein kinase C (PKC)- and mitogen-activated protein kinase kinase (MEK)/extracellular signalregulated kinase (ERK)-dependent pathway, which decreases the protein stability of GCMa. Here we report that PMA increases the ubiquitination level of GCMa, dependent on the phosphorylation of GCMa on serines 328, 378 and 383. We found that this phosphorylation also stimulates the transcriptional activity of GCMa. Our data indicate that the PMA-induced PKC- and MEK/ERKdependent pathway enhances the degradation as well as the transcriptional activity of GCMa. We also examined the impact of this signaling pathway on trophoblasts and the results suggest that the PKC- and MEK/ERK-dependent pathway is involved in the regulation of trophoblast differentiation.
authors.affiliation: College of Pharmacy, Kinjo Gakuin University, Nagoya, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yasui
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miyazawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kitade
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamada
mesh_terms: D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D012694:Serine / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014327:Trophoblasts / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; C491089:GCM1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D012694:Serine; C016658:phorbolol myristate acetate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate