| First Author | Sono T | Year | 2018 |
| Journal | J Bone Miner Metab | Volume | 36 |
| Issue | 4 | Pages | 410-419 |
| PubMed ID | 28770354 | Mgi Jnum | J:317562 |
| Mgi Id | MGI:6856244 | Doi | 10.1007/s00774-017-0855-2 |
| Citation | Sono T, et al. (2018) THRAP3 interacts with and inhibits the transcriptional activity of SOX9 during chondrogenesis. J Bone Miner Metab 36(4):410-419 |
| abstractText | 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. |
