| First Author | Gopinath SD | Year | 2007 |
| Journal | J Cell Sci | Volume | 120 |
| Issue | Pt 17 | Pages | 3086-98 |
| PubMed ID | 17684061 | Mgi Jnum | J:128373 |
| Mgi Id | MGI:3766867 | Doi | 10.1242/jcs.006619 |
| Citation | Gopinath SD, et al. (2007) The RhoA effector mDiaphanous regulates MyoD expression and cell cycle progression via SRF-dependent and SRF-independent pathways. J Cell Sci 120(Pt 17):3086-98 |
| abstractText | Expression of the key muscle transcription factor MyoD is regulated by RhoA GTPase, which is an important regulator of adhesion-dependent signaling. We show that mDiaphanous (mDia)--an adaptor protein that mediates the effects of RhoA on cell motility and the cytoskeleton--is an upstream regulator of MyoD in C2C12 mouse myoblasts. Knockdown of mDia1 reduced MyoD expression and proliferation via a serum-response factor (SRF)-dependent pathway. Surprisingly, overexpression of a Rho-independent form of mDia1 (mDiaDeltaN3), despite activating SRF, also suppressed MyoD and the cell cycle, suggesting the presence of a second pathway downstream of mDia1. We present evidence that the alternative pathway by which mDia1 regulates MyoD involves T-cell factor (TCF)/lymphoid enhancer factor (LEF) and its co-activator, beta-catenin. TCF activity was suppressed by mDiaDeltaN3 and induced by silencing mDia. mDiaDeltaN3 disrupted the signal-dependent nuclear localization of beta-catenin and suppressed MyoD expression. Co-expression of a degradation-resistant form of beta-catenin with mDiaDeltaN3 restored MyoD expression, suggesting a mechanistic link between the two signaling proteins. We also implicate a region encompassing the FH1 domain of mDia1 in beta-catenin-TCF regulation. Taken together, our results suggest that a balance between two pathways downstream of mDia regulates MyoD expression and cell cycle progression. |
