Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling

S. Tsukamoto, T. Mizuta, M. Fujimoto, S. Ohte, K. Osawa, A. Miyamoto, K. Yoneyama, E. Murata, A. Machiya, E. Jimi, S. Kokabu, T. Katagiri

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37 Citations (Scopus)

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.

Original languageEnglish
Article number7596
JournalScientific reports
Volume4
DOIs
Publication statusPublished - Dec 23 2014
Externally publishedYes

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Bone Morphogenetic Proteins
Type I Bone Morphogenetic Protein Receptors
Phosphotransferases
DNA
Phosphorylation
Genes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Tsukamoto, S., Mizuta, T., Fujimoto, M., Ohte, S., Osawa, K., Miyamoto, A., ... Katagiri, T. (2014). Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling. Scientific reports, 4, [7596]. https://doi.org/10.1038/srep07596

Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling. / Tsukamoto, S.; Mizuta, T.; Fujimoto, M.; Ohte, S.; Osawa, K.; Miyamoto, A.; Yoneyama, K.; Murata, E.; Machiya, A.; Jimi, E.; Kokabu, S.; Katagiri, T.

In: Scientific reports, Vol. 4, 7596, 23.12.2014.

Research output: Contribution to journalArticle

Tsukamoto, S, Mizuta, T, Fujimoto, M, Ohte, S, Osawa, K, Miyamoto, A, Yoneyama, K, Murata, E, Machiya, A, Jimi, E, Kokabu, S & Katagiri, T 2014, 'Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling', Scientific reports, vol. 4, 7596. https://doi.org/10.1038/srep07596
Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A et al. Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling. Scientific reports. 2014 Dec 23;4. 7596. https://doi.org/10.1038/srep07596
Tsukamoto, S. ; Mizuta, T. ; Fujimoto, M. ; Ohte, S. ; Osawa, K. ; Miyamoto, A. ; Yoneyama, K. ; Murata, E. ; Machiya, A. ; Jimi, E. ; Kokabu, S. ; Katagiri, T. / Smad9 is a new type of transcriptional regulator in bone morphogenetic protein signaling. In: Scientific reports. 2014 ; Vol. 4.
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