α-Catenin is an inhibitor of transcription

Rebecca L. Daugherty*, Leonid Serebryannyy, Alex Yemelyanov, Annette S. Flozak, Hui Jun Yu, Steven T. Kosak, Primal De Lanerolle, Cara J. Gottardi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5260-5265
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number14
DOIs
StatePublished - 2014

Keywords

  • Alpha-catenin
  • Beta-catenin

ASJC Scopus subject areas

  • General

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