α-Catenin is an inhibitor of transcription.
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.
Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Rebecca L
RL
Daugherty
Leonid
L
Serebryannyy
Alex
A
Yemelyanov
Annette S
AS
Flozak
Hui-Jun
HJ
Yu
Steven T
ST
Kosak
Primal
P
deLanerolle
Cara J
CJ
Gottardi
D045744:Cell Line, Tumor; D006801:Humans; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000502:physiology*; D051178:alpha Catenin / Q000502:physiology*
D051178:alpha Catenin
alpha-catenin; beta-catenin