| First Author | Daugherty RL | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 14 | Pages | 5260-5 |
| PubMed ID | 24706864 | Mgi Jnum | J:208618 |
| Mgi Id | MGI:5563837 | Doi | 10.1073/pnas.1308663111 |
| Citation | Daugherty RL, et al. (2014) alpha-Catenin is an inhibitor of transcription. Proc Natl Acad Sci U S A 111(14):5260-5 |
| abstractText | alpha-Catenin (alpha-cat) is an actin-binding protein required for cell-cell cohesion. Although this adhesive function for alpha-cat is well appreciated, cells contain a substantial amount of nonjunctional alpha-cat that may be used for other functions. We show that alpha-cat is a nuclear protein that can interact with beta-catenin (beta-cat) and T-cell factor (TCF) and that the nuclear accumulation of alpha-cat depends on beta-cat. Using overexpression, knockdown, and chromatin immunoprecipitation approaches, we show that alpha-cat attenuates Wnt/beta-cat-responsive genes in a manner that is downstream of beta-cat/TCF loading on promoters. Both beta-cat- and actin-binding domains of alpha-cat are required to inhibit Wnt signaling. A nuclear-targeted form of alpha-cat induces the formation of nuclear filamentous actin, whereas cells lacking alpha-cat show altered nuclear actin properties. Formation of nuclear actin filaments correlates with reduced RNA synthesis and altered chromatin organization. Conversely, nuclear extracts made from cells lacking alpha-cat show enhanced general transcription in vitro, an activity that can be partially rescued by restoring the C-terminal actin-binding region of alpha-cat. These data demonstrate that alpha-cat may limit gene expression by affecting nuclear actin organization. |
