Details

Autor(en) / Beteiligte

• Daugherty, Rebecca L.
• Serebryannyy, Leonid
• Yemelyanov, Alex
• Flozak, Annette S.
• Yu, Hui-Jun
• Kosak, Steven T.
• deLanerolle, Primal
• Gottardi, Cara J.

Titel

α-Catenin is an inhibitor of transcription

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2014-04, Vol.111 (14), p.5260-5265

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• α-Catenin (α-cat) is an actin-binding protein required for cell–cell cohesion. Although this adhesive function for α-cat is well appreciated, cells contain a substantial amount of nonjunctional α-cat that may be used for other functions. We show that α-cat is a nuclear protein that can interact with β-catenin (β-cat) and T-cell factor (TCF) and that the nuclear accumulation of α-cat depends on β-cat. Using overexpression, knockdown, and chromatin immunoprecipitation approaches, we show that α-cat attenuates Wnt/β-cat–responsive genes in a manner that is downstream of β-cat/TCF loading on promoters. Both β-cat– and actin-binding domains of α-cat are required to inhibit Wnt signaling. A nuclear-targeted form of α-cat induces the formation of nuclear filamentous actin, whereas cells lacking α-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 α-cat show enhanced general transcription in vitro, an activity that can be partially rescued by restoring the C-terminal actin-binding region of α-cat. These data demonstrate that α-cat may limit gene expression by affecting nuclear actin organization.