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?-Catenin is an inhibitor of transcription.


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

SUBMITTER: Daugherty RL 

PROVIDER: S-EPMC3986139 | BioStudies | 2014-01-01T00:00:00Z

REPOSITORIES: biostudies

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