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Differences in the Nuclear Export Mechanism between Myocardin and Myocardin-related Transcription Factor A
Authors:Ken'ichiro Hayashi  Tsuyoshi Morita
Affiliation:From the Department of Neuroscience (D13), Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
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.
Keywords:Cell Biology   Nuclear Transport   Protein/Protein Interactions   Smooth Muscle   Transcription Coactivators   CRM1   G-actin   MRTF-A/B   Myocardin   Serum Response Factor
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