| First Author | Quinn ZA | Year | 2001 |
| Journal | Nucleic Acids Res | Volume | 29 |
| Issue | 3 | Pages | 732-42 |
| PubMed ID | 11160896 | Mgi Jnum | J:172903 |
| Mgi Id | MGI:5009194 | Doi | 10.1093/nar/29.3.732 |
| Citation | Quinn ZA, et al. (2001) Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins. Nucleic Acids Res 29(3):732-42 |
| abstractText | An emerging theme in transforming growth factor-ss (TGF-ss) signalling is the association of the Smad proteins with diverse groups of transcriptional regulatory proteins. Several Smad cofactors have been identified to date but the diversity of TGF-ss effects on gene transcription suggests that interactions with other co-regulators must occur. In these studies we addressed the possible interaction of Smad proteins with the myocyte enhancer-binding factor 2 (MEF2) transcriptional regulators. Our studies indicate that Smad2 and 4 (Smad2/4) complexes cooperate with MEF2 regulatory proteins in a GAL4-based one-hybrid reporter gene assay. We have also observed in vivo interactions between Smad2 and MEF2A using co-immunoprecipitation assays. This interaction is confirmed by glutathione S:-transferase pull-down analysis. Immunofluorescence studies in C2C12 myotubes show that Smad2 and MEF2A co-localise in the nucleus of multinuclear myotubes during differentiation. Interestingly, phospho-acceptor site mutations of MEF2 that render it unresponsive to p38 MAP kinase signalling abrogate the cooperativity with the Smads suggesting that p38 MAP Kinase-catalysed phosphorylation of MEF2 is a prerequisite for the Smad-MEF2 interaction. Thus, the association between Smad2 and MEF2A may subserve a physical link between TGF-ss signalling and a diverse array of genes controlled by the MEF2 cis element. |
