| First Author | Pawłowski R | Year | 2010 |
| Journal | EMBO J | Volume | 29 |
| Issue | 20 | Pages | 3448-58 |
| PubMed ID | 20818336 | Mgi Jnum | J:165431 |
| Mgi Id | MGI:4837297 | Doi | 10.1038/emboj.2010.216 |
| Citation | Pawlowski R, et al. (2010) An actin-regulated importin alpha/beta-dependent extended bipartite NLS directs nuclear import of MRTF-A. EMBO J 29(20):3448-58 |
| abstractText | Myocardin-related transcription factors (MRTFs) are actin-regulated transcriptional coactivators, which bind G-actin through their N-terminal RPEL domains. In response to signal-induced actin polymerisation and concomitant G-actin depletion, MRTFs accumulate in the nucleus and activate target gene transcription through their partner protein SRF. Nuclear accumulation of MRTFs in response to signal is inhibited by increased G-actin level. Here, we study the mechanism by which MRTF-A enters the nucleus. We show that MRTF-A contains an unusually long bipartite nuclear localisation signal (NLS), comprising two basic elements separated by 30 residues, embedded within the RPEL domain. Using siRNA-mediated protein depletion in vivo, and nuclear import assays in vitro, we show that the MRTF-A extended bipartite NLS uses the importin (Imp)alpha/beta-dependent import pathway, and that import is inhibited by G-actin. Interaction of the NLS with the Impalpha-Impbeta heterodimer requires both NLS basic elements, and is dependent on the Impalpha major and minor binding pockets. Binding of the Impalpha-Impbeta heterodimer to the intact MRTF-A RPEL domain occurs competitively with G-actin. Thus, MRTF-A contains an actin-sensitive nuclear import signal. |
