title: Arp5 is a key regulator of myocardin in smooth muscle cells.
abstract: Myocardin (Myocd) and Myocd-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). RPEL motifs are monomeric globular actin (G-actin) binding elements that regulate MRTF localization and activity. However, the function of the RPEL motif in Myocd is largely unknown because of its low affinity for G-actin. Here, we demonstrated that the Myocd RPEL motif bound to actin-related protein 5 (Arp5) instead of conventional actin, resulting in a significant suppression of Myocd activity. In addition, Arp5 bound to a DNA binding domain of SRF via its C-terminal sequence and prevented the association of the Myocd-SRF complex with the promoter regions of smooth muscle genes. Well-differentiated smooth muscle cells mainly expressed a specific splicing variant of arp5; therefore, the protein level of Arp5 was markedly reduced by partial messenger RNA decay and translational suppression. In dedifferentiated smooth muscle cells, Arp5 knockdown restored the differentiated phenotype via Myocd activation. Thus, Arp5 is a key regulator of Myocd activity.
authors.affiliation: Department of Neuroscience, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Morita
authors.forename: Ken'ichiro
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D010641:Phenotype; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D016415:Sequence Alignment; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D000091308:Angiopoietin-Like Protein 6; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin; C477601:ANGPTL6 protein, human