title: Importance of dimer formation of myocardin family members in the regulation of their nuclear export.
abstract: Myocardin (Mycd) family members function as a transcriptional cofactor for serum response factor (SRF). Dimer formation is necessary to exhibit their function, and the coiled-coil domain (CC) plays a critical role in their dimerization. We have recently revealed a detailed molecular mechanism for their Crm1 (exportin1)-mediated nuclear export. Here, we found other unique significances of the dimerization of Mycd family members. Introduction of mutations in the CC of myocardin-related transcription factor A (MRTF-A) and truncated Mycd resulted in significant decreases in their cytoplasmic localization and increases in their nuclear localization. In accordance with such subcellular localization changes, their binding to Crm1 were reduced. These results indicate that the dimerization of Mycd family members is necessary for their Crm1-mediated nuclear export. We have recently found that the N-terminal region of Mycd consisting of 128 amino acids (Mycd N128) self-associates to Mycd via the central basic domain (CB), resulting in masking the Crm1-binding site. Such self-association of MRTF-A would be unlikely. In this study, we also revealed that the dimerization of Mycd was also necessary for this self-association. Wild-type Mycd activated SRF-mediated transcription more potently than Mycd lacking the Mycd N128 (Mycd ΔN128) did. These results suggest two possible functions of the Mycd N128: 1) stabilization of Mycd dimer to enhance SRF-mediated transcription and 2) positive regulation of the transactivation ability of Mycd. These findings provide a new insight into the functional regulation of Mycd family members.
authors.affiliation: Department of Neuroscience, Osaka University Graduate School of Medicine, Japan. khayashi@nbiochem.med.osaka-u.ac.jp
authors.forename: Ken'ichiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Morita
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism; D028884:Karyopherins / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D055503:Protein Multimerization / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D000097606:Exportin 1 Protein; D000099251:Myocardin
chemical_list: D004268:DNA-Binding Proteins; D028884:Karyopherins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D026362:Serum Response Factor; D015534:Trans-Activators; D000097606:Exportin 1 Protein; D000099251:Myocardin