Smad7:β-catenin Complex Regulates Myogenic Gene Transcription
| dc.contributor.author | McDermott, John | |
| dc.contributor.author | Tripathi, Soma | |
| dc.contributor.author | Tetsuake, Miyake | |
| dc.date.accessioned | 2020-02-14T20:17:46Z | |
| dc.date.available | 2020-02-14T20:17:46Z | |
| dc.date.issued | 2019 | |
| dc.description.abstract | Recent reports indicate that Smad7 promotes skeletal muscle differentiation and growth. We previously documented a non-canonical role of nuclear Smad7 during myogenesis, independent of its role in TGF-β signaling. Here further characterization of the myogenic function of Smad7 revealed β-catenin as a Smad7 interacting protein. Biochemical analysis identified a Smad7 interaction domain (SID) between aa575 and aa683 of β-catenin. Reporter gene analysis and chromatin immunoprecipitation demonstrated that Smad7 and β-catenin are cooperatively recruited to the extensively characterized ckm promoter proximal region to facilitate its muscle restricted transcriptional activation in myogenic cells. Depletion of endogenous Smad7 and β-catenin in muscle cells reduced ckm promoter activity indicating their role during myogenesis. Deletion of the β-catenin SID substantially reduced the effect of Smad7 on the ckm promoter and exogenous expression of SID abolished β-catenin function, indicating that SID functions as a trans dominant-negative regulator of β-catenin activity. β-catenin interaction with the Mediator kinase complex through its Med12 subunit led us to identify MED13 as an additional Smad7-binding partner. Collectively, these studies document a novel function of a Smad7-MED12/13-β-catenin complex at the ckm locus, indicating a key role of this complex in the program of myogenic gene expression underlying skeletal muscle development and regeneration. | en_US |
| dc.description.sponsorship | York University Libraries | en_US |
| dc.identifier.citation | Tripathi, S., Miyake, T. & McDermott, J.C. Smad7:β-catenin complex regulates myogenic gene transcription. Cell Death Dis 10, 387 (2019). https://doi.org/10.1038/s41419-019-1615-0 | en_US |
| dc.identifier.uri | https://doi.org/10.1038/s41419-019-1615-0 | en_US |
| dc.identifier.uri | https://hdl.handle.net/10315/36992 | |
| dc.language.iso | en | en_US |
| dc.publisher | Springer Nature | en_US |
| dc.rights | Attribution 2.5 Canada | * |
| dc.rights.article | https://www.nature.com/articles/s41419-019-1615-0 | en_US |
| dc.rights.journal | https://www.nature.com/cddis/ | en_US |
| dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ca/ | * |
| dc.title | Smad7:β-catenin Complex Regulates Myogenic Gene Transcription | en_US |
| dc.type | Article | en_US |