title: Smad8/9 Is Regulated Through the BMP Pathway.
abstract: Members of the transforming growth factor-β (TGF-β) family function through Smad-dependent and Smad-independent pathways. The Smad-dependent pathway is stimulated through the phosphorylation of receptor-regulated Smad (R-Smad) and inhibited through the dephosphorylation of R-Smad or the gene induction of inhibitory Smad (I-Smad). Little information is available on the regulation of R-Smad gene expression. BMP4 potentiated the up-regulation of Smad8/9 expression in C2C12, H9c2, 3T3-L1, HepG2, B16, and primary fibroblasts. BMP4-induced Smad8/9 expression was cycloheximide-insensitive and LDN-193189-sensitive, suggesting a direct event mediated through BMP type I receptors. BMP4 transcriptionally stimulated the Smad8/9 gene, and BMP-responsive elements (BREs) spanning nt -121 to nt -44 are involved in the up-regulation of Smad8/9 expression in response to BMP4. Phosphorylated Smad1/5/8/9 specifically bound to the BREs of Smad8/9 gene. The present study reveals that Smad8/9 is a unique R-Smad regulated through the BMP pathway at the mRNA level. J. Cell. Biochem. 117: 1788-1796, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratory of Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara, 252-5201, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Katakawa
authors.affiliation: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Funaba
authors.affiliation: Laboratory of Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara, 252-5201, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Murakami
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D051904:Smad8 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C525809:BMP4 protein, human; C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C107514:SMAD9 protein, human; D051904:Smad8 Protein; C491621:Smad9 protein, mouse
keywords: BMP; SMAD8/9; TRANSCRIPTION