THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis

Springer Science and Business Media LLC - Tập 36 - Trang 410-419 - 2017
Takashi Sono1, Haruhiko Akiyama2, Shigenori Miura3, Jian Min Deng4, Chisa Shukunami3,5, Yuji Hiraki3, Yu Tsushima6, Yoshiaki Azuma7, Richard R. Behringer4, Shuichi Matsuda1
1Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
2Department of Orthopaedic Surgery, Gifu University, Gifu, Japan
3Laboratory of Cellular Differentiation, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
4Department of Genetics, University of Texas M. D. Anderson Cancer Center, Houston, USA
5Department of Molecular Biology and Biochemistry, Division of Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
6Pharmacology Research Department, Teijin Pharma Limited, Hino, Japan
7Medical Science Department, Teijin Pharma Limited, Tokyo, Japan

Tóm tắt

Sex-determining region Y (Sry)-box (Sox)9 is required for chondrogenesis as a transcriptional activator of genes related to chondrocyte proliferation, differentiation, and cartilage-specific extracellular matrix. Although there have been studies investigating the Sox9-dependent transcriptional complexes, not all their components have been identified. In the present study, we demonstrated that thyroid hormone receptor-associated protein (THRAP)3 is a component of a SOX9 transcriptional complex by liquid chromatography mass spectrometric analysis of FLAG-tagged Sox9-binding proteins purified from FLAG-HA-tagged Sox9 knock-in mice. Thrap3 knockdown in ATDC5 chondrogenic cells increased the expression of Collagen type II alpha 1 chain (Col2a1) without affecting Sox9 expression. THRAP3 and SOX9 overexpression reduced Col2a1 levels to a greater degree than overexpression of SOX9 alone. The negative regulation of SOX9 transcriptional activity by THRAP3 was mediated by interaction between the proline-, glutamine-, and serine-rich domain of SOX9 and the innominate domain of THRAP3. These results indicate that THRAP3 negatively regulates SOX9 transcriptional activity as a cofactor of a SOX9 transcriptional complex during chondrogenesis.

Tài liệu tham khảo

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