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SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix

Author

Listed:
  • Masatoshi Fukuda

    (Kumamoto University
    Kumamoto University)

  • Tatsuya Yoshizawa

    (Kumamoto University)

  • Md. Fazlul Karim

    (Kumamoto University)

  • Shihab U. Sobuz

    (Kumamoto University)

  • Wataru Korogi

    (Kumamoto University
    Kumamoto University)

  • Daiki Kobayasi

    (Kumamoto University)

  • Hiroki Okanishi

    (Kumamoto University)

  • Masayoshi Tasaki

    (Kumamoto University
    Kumamoto University)

  • Katsuhiko Ono

    (Kumamoto University)

  • Tomohiro Sawa

    (Kumamoto University)

  • Yoshifumi Sato

    (Kumamoto University)

  • Mami Chirifu

    (Kumamoto University)

  • Takeshi Masuda

    (Kumamoto University)

  • Teruya Nakamura

    (Kumamoto University)

  • Hironori Tanoue

    (Kumamoto University)

  • Kazuhisa Nakashima

    (Tsurumi University School of Dental Medicine)

  • Yoshihiro Kobashigawa

    (Kumamoto University)

  • Hiroshi Morioka

    (Kumamoto University)

  • Eva Bober

    (Max-Planck-Institute for Heart and Lung Research)

  • Sumio Ohtsuki

    (Kumamoto University)

  • Yuriko Yamagata

    (Kumamoto University)

  • Yukio Ando

    (Kumamoto University
    Kumamoto University)

  • Yuichi Oike

    (Kumamoto University
    Kumamoto University)

  • Norie Araki

    (Kumamoto University)

  • Shu Takeda

    (Tokyo Medical and Dental University)

  • Hiroshi Mizuta

    (Kumamoto University)

  • Kazuya Yamagata

    (Kumamoto University
    Kumamoto University)

Abstract

SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.

Suggested Citation

  • Masatoshi Fukuda & Tatsuya Yoshizawa & Md. Fazlul Karim & Shihab U. Sobuz & Wataru Korogi & Daiki Kobayasi & Hiroki Okanishi & Masayoshi Tasaki & Katsuhiko Ono & Tomohiro Sawa & Yoshifumi Sato & Mami , 2018. "SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05187-4
    DOI: 10.1038/s41467-018-05187-4
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