@article{23f7ee48ba394513b258dda6e4d0770f,
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 (SmadDVD). Transcriptional activity of Smad9DVD was lower than that of Smad1DVD or Smad5DVD, even though all three SmadDVDs 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 Smad1DVD. 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.",
author = "S. Tsukamoto and T. Mizuta and M. Fujimoto and S. Ohte and K. Osawa and A. Miyamoto and K. Yoneyama and E. Murata and A. Machiya and E. Jimi and S. Kokabu and T. Katagiri",
note = "Funding Information: We thank Seiya Suzuki, Mitsue Fujiwara and Ayaka Mizuguchi for their excellent technical assistance and the members of the Division of Pathophysiology for valuable discussion. We are grateful to Dr. J. A. Langer for kindly providing pcDEF3 and Dr. Michio Shiibashi for statistical analysis. This work was supported in part by the following sources: a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to ST, 25893228; KY, 24592278; TK, 25293326 and 25670658; EJ: 23390424); a Grant-in-Aid from the Support Project for the Formation of a Strategic Center in a Private University from the Ministry of Education, Culture, Sports, Science and Technology of Japan (TK); and the Health and Labor Sciences Research Grants for Research on Measures for Intractable Diseases from the Ministry of Health, Labor, and Welfare of Japan (TK).",
year = "2014",
month = dec,
day = "23",
doi = "10.1038/srep07596",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}