title: Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling.
abstract: Smad1, Smad5 and Smad9 (also known as Smad8) are activated by phosphorylation by bone morphogenetic protein (BMP)-bound type I receptor kinases. We examined the role of Smad1, Smad5, and Smad9 by creating constitutively active forms (Smad(DVD)). Transcriptional activity of Smad9(DVD) was lower than that of Smad1(DVD) or Smad5(DVD), even though all three Smad(DVD)s associated with Smad4 and bound to the target DNA. The linker region of Smad9 was sufficient to reduce transcriptional activity. Smad9 expression was increased by the activation of BMP signaling, similar to that of inhibitory Smads (I-Smads), and Smad9 reduced BMP activity. In contrast to I-Smads, however, Smad9 did not inhibit the type I receptor kinase and suppressed the constitutively active Smad1(DVD). Smad9 formed complexes with Smad1 and bound to DNA but suppressed the transcription of the target gene. Taken together, our findings suggest that Smad9 is a new type of transcriptional regulator in BMP signaling.
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tsukamoto
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizuta
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ohte
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Osawa
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Miyamoto
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoneyama
authors.affiliation: School of Medical Technology and Health, Faculty of Health and Medical Care, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Murata
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Machiya
authors.affiliation: Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu-shi, Fukuoka 803-8580, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Jimi
authors.affiliation: 1] Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan [2] Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kokabu
authors.affiliation: Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Katagiri
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism*; D051904:Smad8 Protein / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051904:Smad8 Protein; C491621:Smad9 protein, mouse