title: Differences in the nuclear export mechanism between myocardin and myocardin-related transcription factor A.
abstract: Myocardin (Mycd), a key factor in smooth muscle cell differentiation, is constitutively located in the nucleus, whereas myocardin-related transcription factors A and B (MRTF-A/B) reside mostly in the cytoplasm and translocate to the nucleus in a Rho-dependent manner. Here, we investigated the nuclear export of Mycd family members. They possess two leucine-rich sequences: L1 in the N terminus and L2 in the Gln-rich domain. Although L2 (but not L1) served as a CRM1-binding site for Mycd, CRM1-mediated nuclear export did not affect its subcellular localization. Serum response factor (SRF) competitively inhibited Mycd/CRM1 interaction. Furthermore, such interaction was autonomously inhibited. The N terminus of Mycd bound intramolecularly to Mycd, resulting in masking L2. In contrast, the CRM1-binding affinity of MRTF-A was much higher than that of Mycd because both L1 and L2 of MRTF-A served as functional CRM1-binding sites, and the autoinhibition observed in the Mycd/CRM1 interaction was absent in the MRTF-A/CRM1 interaction. Additionally, because the SRF-binding affinity of MRTF-A was lower than that of Mycd, the inhibitory effect of SRF on the MRTF-A/CRM1 interaction was weak. Thus, MRTF-A is much more likely to be exported from the nucleus. These differences could be the reason for the distinct subcellular localization of Mycd and MRTF-A.
authors.affiliation: Department of Neuroscience (D13), Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, 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: D000199:Actins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D028884:Karyopherins / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000097606:Exportin 1 Protein; D000099251:Myocardin
chemical_list: D000199:Actins; D028884:Karyopherins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000097606:Exportin 1 Protein; D000099251:Myocardin; C557977:myocardin-related transcription factor-A, rat; C569168:myocardin-related transcription factor-B, rat