α-Catulin, a Rho signalling component, can regulate NF-κB through binding to IKK-β, and confers resistance to apoptosis

Abstract

Rho GTPases regulate diverse cellular functions including adhesion, cytokinesis and motility, as well as the activity of the transcription factors NF-jB, serum response factor and C/EBP. a-Catulin, an a-catenin-related protein that shares structural similarities with cytoskeletal linker proteins, facilitates Rho signalling by serving as a scaffold for the Rho-specific guanine nucleotide exchange factor Lbc. We report here that a-catulin also interacts with a key component of the NF-jB signalling pathway, namely the IjB kinase (IKK)-b. In co-immunoprecipitations, a-catulin can bind IKK-b and Lbc. Ectopic expression of a-catulin augmented NF-jB activity, promoted cell migration and increased resistance to apoptosis, whereas knockdown experiments showed the opposite effects. Together, these features suggest that a-catulin has tumorigenic potential.

α-Dystrobrevin-1 recruits α-catulin to the α 1D -adrenergic receptor/dystrophin-associated protein complex signalosome

“…For example, α-catulin has been shown to directly bind and modulate the enzymatic activity of LbcRho guanine exchange factor (GEF), IkB kinase, and Ras (23)(24)(25). More recently, siRNA screens performed in Caenorhabditis elegans suggest that α-catulin facilitates proper localization and function of the BK channel SLO-1 (21, 37), and it is likely that α-DB1 recruits α-catulin to the BK channel, considering the high sequence homology in α-DB1 C-terminal domains across species (Fig.…”

“…What is the functional purpose of α-catulin in the α 1D -AR/DAPC signalosome? Previous studies indicate that α-catulin may facilitate intracellular signaling mechanisms by scaffolding essential downstream effectors in close proximity to one another (23)(24)(25). To determine whether α-catulin performs a similar function in the α 1D -AR/Gαq/11 signaling pathway, we examined the effects of overexpressing or knocking down α-catulin on α 1D -AR signaling.…”

α-Catulin Drives Metastasis by Activating ILK and Driving an αvβ3 Integrin Signaling Axis

“…The Rho family has been shown to play important roles in focal adhesion formation and in the organization of the actin cytoskeleton (8). a-Catulin may also play a role in cancer because it can directly interact with inhibitor of IkB kinase (IKK)-b and activate NFkB signaling, which promotes cancer cell migration and resistance to apoptosis (9). We recently reported that a-catulin is upregulated in both cancer cell lines and oral squamous cell carcinomas, and knocking down a-catulin induces cellular senescence (10).…”

α-Catulin knockdown induces senescence in cancer cells

“…The a-CATULIN/CTNNAL1 gene localizes to chromosome 9q31-32 (Zhang et al, 1998;Park et al, 2002), a frequent site of allelic loss and a tumor suppressor marker that has been reported in many human cancers (Schultz et al, 1995;Miura et al, 1996), which implies that a-catulin may be a tumor suppressor. However, other studies (Park et al, 2002;Wiesner et al, 2008) report that a-catulin has tumorigenic potential because it binds directly to IKK-b and Lbc, a Rho-specific guanine nucleotide exchange factor, which promotes cell migration and increases resistance to apoptosis. The literature contains little evidence of the clinical significance and function of a-catulin in cancer progression.…”