TY - JOUR
T1 - α-Catenin is an inhibitor of transcription
AU - Daugherty, Rebecca L.
AU - Serebryannyy, Leonid
AU - Yemelyanov, Alex
AU - Flozak, Annette S.
AU - Yu, Hui Jun
AU - Kosak, Steven T.
AU - De Lanerolle, Primal
AU - Gottardi, Cara J.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Alpha-catenin
KW - Beta-catenin
UR - http://www.scopus.com/inward/record.url?scp=84898034117&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898034117&partnerID=8YFLogxK
U2 - 10.1073/pnas.1308663111
DO - 10.1073/pnas.1308663111
M3 - Article
C2 - 24706864
AN - SCOPUS:84898034117
SN - 0027-8424
VL - 111
SP - 5260
EP - 5265
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 14
ER -