Investigation of cell function from the point of view of the regulatory mechanism for cellular localization of myocardin family members

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Myocardin (Mycd), a key factor for the smooth muscle cell differentiation, is constitutively located in the nucleus, whereas myocardin-related transcription factors A and B (MRTF-A/B), mostly reside in the cytoplasm and translocate to the nucleus in response to a signaling-induced decrease in G-actin. MRTF-A/B play a critical role in induction of epithelial-mesenchymal transition (EMT). Here, we investigated the regulatory mechanism for subcellular localization of Mycd family members and their related cell functions. Our studies revealed the following findings. 1) Regulatory mechanism of Crm1-mediated nuclear export of Mycd family members: critical differences in the regulation between Mycd and MRTF-A/B. 2) Inhibitory mechanism of CCG-1423 (a novel inhibitor of EMT) for the nuclear import of MRTF-A/B. 3) Activation of MRTF-A nuclear import by thymosin beta 4. 4) Novel function of Mycd RPEL motifs: actinrelated protein 5-mediated inhibition of Mycd function.