| First Author | Morita T | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 437 |
| Issue | 3 | Pages | 331-5 |
| PubMed ID | 23811404 | Mgi Jnum | J:205323 |
| Mgi Id | MGI:5544560 | Doi | 10.1016/j.bbrc.2013.06.069 |
| Citation | Morita T, et al. (2013) G-actin sequestering protein thymosin-beta4 regulates the activity of myocardin-related transcription factor. Biochem Biophys Res Commun 437(3):331-5 |
| abstractText | Myocardin-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). MRTFs contain three copies of the RPEL motif at their N-terminus, and they bind to monomeric globular actin (G-actin). Previous studies illustrate that G-actin binding inhibits MRTF activity by preventing the MRTFs nuclear accumulation. In the living cells, the majority of G-actin is sequestered by G-actin binding proteins that prevent spontaneous actin polymerization. Here, we demonstrate that the most abundant G-actin sequestering protein thymosin-beta4 (Tbeta4) was involved in the regulation of subcellular localization and activity of MRTF-A. Tbeta4 competed with MRTF-A for G-actin binding; thus, interfering with G-actin-MRTF-A complex formation. Tbeta4 overexpression induced the MRTF-A nuclear accumulation and activation of MRTF-SRF signaling. The activation rate of MRTF-A by the Tbeta4 mutant L17A, whose affinity for G-actin is very low, was lower than that by wild-type Tbeta4. In contrast, the beta-actin mutant 3DA, which has a lower affinity for Tbeta4, more effectively suppressed MRTF-A activity than wild-type beta-actin. Furthermore, ectopic Tbeta4 increased the endogenous expression of SRF-dependent actin cytoskeletal genes. Thus, Tbeta4 is an important MRTF regulator that controls the G-actin-MRTFs interaction. |
