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 Gottardi

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 - Jan 1 2014

Fingerprint

Catenins
Cats
Actins
TCF Transcription Factors
Microfilament Proteins
Chromatin Immunoprecipitation
Nuclear Proteins
Cell Extracts
Actin Cytoskeleton

Keywords

  • Alpha-catenin
  • Beta-catenin

ASJC Scopus subject areas

  • General

Cite this

Daugherty, Rebecca L. ; Serebryannyy, Leonid ; Yemelyanov, Alex ; Flozak, Annette S. ; Yu, Hui Jun ; Kosak, Steven T ; De Lanerolle, Primal ; Gottardi, Cara. / α-Catenin is an inhibitor of transcription. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 14. pp. 5260-5265.
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α-Catenin is an inhibitor of transcription. / Daugherty, Rebecca L.; Serebryannyy, Leonid; Yemelyanov, Alex; Flozak, Annette S.; Yu, Hui Jun; Kosak, Steven T; De Lanerolle, Primal; Gottardi, Cara.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 14, 01.01.2014, p. 5260-5265.

Research output: Contribution to journalArticle

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AU - Daugherty, Rebecca L.

AU - Serebryannyy, Leonid

AU - Yemelyanov, Alex

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AU - Yu, Hui Jun

AU - Kosak, Steven T

AU - De Lanerolle, Primal

AU - Gottardi, Cara

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