| First Author | Coubrough ML | Year | 2006 |
| Journal | Exp Cell Res | Volume | 312 |
| Issue | 19 | Pages | 3880-91 |
| PubMed ID | 17011548 | Mgi Jnum | J:306174 |
| Mgi Id | MGI:6708070 | Doi | 10.1016/j.yexcr.2006.08.023 |
| Citation | Coubrough ML, et al. (2006) Impaired nuclear import of mammalian Dlx4 proteins as a consequence of rapid sequence divergence. Exp Cell Res 312(19):3880-91 |
| abstractText | Dlx genes encode a developmentally important family of transcription factors with a variety of functions and sites of action during vertebrate embryogenesis. The murine Dlx4 gene is an enigmatic member of the family; little is known about the normal developmental function(s) of Dlx4. Here, we show that Dlx4 is expressed in the murine placenta and in a trophoblast cell line where the protein localizes to both the nucleus and cytoplasm. Despite the presence of several leucine/valine-rich motifs that match known nuclear export sequences, cytoplasmic Dlx4 is not due to CRM-1-mediated nuclear export. Rather, nuclear import of Dlx4 is compromised by specific residues that flank the nuclear localization signal. One of these residues represents a novel conserved feature of the Dlx4 protein in placental mammals, and the second represents novel variation within mouse Dlx4 isoforms. Comparison of orthologous protein sequences reveals a particularly high rate of non-synonymous change in the coding regions of mammalian Dlx4 genes. Since impaired nuclear localization is unlikely to enhance the function of a nuclear transcription factor, these data point to reduced selection pressure as the basis for the rapid divergence of the Dlx4 gene within the mammalian clade. |
