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

被引：92

作者：

Fukuda, Masatoshi ^{[1
,2
]}

Yoshizawa, Tatsuya ^{[1
]}

Karim, Md Fazlul ^{[1
]}

Sobuz, Shihab U. ^{[1
]}

Korogi, Wataru ^{[1
,2
]}

Kobayasi, Daiki ^{[3
]}

Okanishi, Hiroki ^{[3
]}

Tasaki, Masayoshi ^{[4
,5
]}

Ono, Katsuhiko ^{[6
]}

Sawa, Tomohiro ^{[6
]}

Sato, Yoshifumi ^{[1
]}

Chirifu, Mami ^{[7
]}

Masuda, Takeshi ^{[8
]}

Nakamura, Teruya ^{[7
]}

Tanoue, Hironori ^{[9
]}

Nakashima, Kazuhisa ^{[10
]}

Kobashigawa, Yoshihiro ^{[11
]}

Morioka, Hiroshi ^{[11
]}

Bober, Eva ^{[12
]}

Ohtsuki, Sumio ^{[8
]}

Yamagata, Yuriko ^{[7
]}

Ando, Yukio ^{[5
,13
]}

Oike, Yuichi ^{[9
,13
]}

Araki, Norie ^{[3
]}

Takeda, Shu ^{[14
]}

Mizuta, Hiroshi ^{[2
]}

Yamagata, Kazuya ^{[1
,13
]}

机构：

[1] Kumamoto Univ, Fac Life Sci, Dept Med Biochem, Kumamoto 8608556, Japan

[2] Kumamoto Univ, Fac Life Sci, Dept Orthopaed Surg, Kumamoto 8608556, Japan

[3] Kumamoto Univ, Fac Life Sci, Dept Tumor Genet & Biol, Kumamoto 8608556, Japan

[4] Kumamoto Univ, Fac Life Sci, Dept Morphol & Physiol Sci, Kumamoto 8608556, Japan

[5] Kumamoto Univ, Fac Life Sci, Dept Neurol, Kumamoto 8608556, Japan

[6] Kumamoto Univ, Fac Life Sci, Dept Microbiol, Kumamoto 8608556, Japan

[7] Kumamoto Univ, Fac Life Sci, Dept Struct Biol, Kumamoto 8608556, Japan

[8] Kumamoto Univ, Fac Life Sci, Dept Pharmaceut Microbiol, Kumamoto 8608556, Japan

[9] Kumamoto Univ, Fac Life Sci, Dept Mol Genet, Kumamoto 8608556, Japan

[10] Tsurumi Univ, Dept Pharmacol, Sch Dent Med, Yokohama, Kanagawa 2308501, Japan

[11] Kumamoto Univ, Fac Life Sci, Dept Analyt & Biophys Chem, Kumamoto 8608556, Japan

[12] Max Planck Inst Heart & Lung Res, Dept Cardiac Dev & Remodeling, Ludwigstr 43, D-61231 Bad Nauheim, Germany

[13] Kumamoto Univ, Fac Life Sci, Ctr Metab Regulat Hlth Aging, Kumamoto 8608556, Japan

[14] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Tokyo 1138519, Japan

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

TRANSCRIPTION FACTOR OSTERIX; OSTEOBLAST DIFFERENTIATION; OSTEOGENIC ACTIVITY; BETA-CATENIN; STEM-CELLS; METABOLISM; INHIBITION; SIRTUINS; DEACETYLATION; ACTIVATION;

D O I：

10.1038/s41467-018-05187-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：14

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[1]

PIASxβ is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts [J].