Loading...
Please wait, while we are loading the content...
Similar Documents
Smad7 Protein Interacts with Receptor-regulated Smads (R-Smads) to Inhibit Transforming Growth Factor-β (TGF-β)/Smad Signaling
| Content Provider | Scilit |
|---|---|
| Author | Yan, Xiaohua Liao, Hongwei Cheng, Minzhang Shi, Xiaojing Lin, Xia Feng, Xin-Hua Chen, Ye-Guang |
| Copyright Year | 2016 |
| Description | Journal: Journal of Biological Chemistry TGF-β is a pleiotropic cytokine that regulates a wide range of cellular actions and pathophysiological processes. TGF-β signaling is spatiotemporally fine-tuned. As a key negative regulator of TGF-β signaling, Smad7 exerts its inhibitory effects by blocking receptor activity, inducing receptor degradation or interfering with Smad-DNA binding. However, the functions and the molecular mechanisms underlying the actions of Smad7 in TGF-β signaling are still not fully understood. In this study we report a novel mechanism whereby Smad7 antagonizes TGF-β signaling at the Smad level. Smad7 oligomerized with R-Smad proteins upon TGF-β signaling and directly inhibited R-Smad activity, as assessed by Gal4-luciferase reporter assays. Mechanistically, Smad7 competes with Smad4 to associate with R-Smads and recruits the E3 ubiquitin ligase NEDD4L to activated R-Smads, leading to their polyubiquitination and proteasomal degradation. Similar to the R-Smad-Smad4 oligomerization, the interaction between R-Smads and Smad7 is mediated by their mad homology 2 (MH2) domains. A positive-charged basic region including the L3/β8 loop-strand module and adjacent amino acids in the MH2 domain of Smad7 is essential for the interaction. These results shed new light on the regulation of TGF-β signaling by Smad7. |
| Related Links | http://www.jbc.org/content/291/1/382.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697173/pdf http://www.jbc.org/article/S0021925820362657/pdf |
| Ending Page | 392 |
| Page Count | 11 |
| Starting Page | 382 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m115.694281 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 1 |
| Volume Number | 291 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2016-01-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Smad Transcription Factor Cell Signaling Protein Degradation Protein-protein Interaction Signaling Regulation Transforming Growth Factor Beta (tgf-b) Ubiquitylation (ubiquitination) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
