ABSTRACT
A variety of pathophysiological situations that affect cells of the vasculature, including endothelial and smooth muscle cells, leads to the expression of genes such as adhesion molecules and chemokines that are dependent on members of the nuclear factor (NF)-kappaB family of transcription factors. The corresponding gene products mediate important biological functions such as immune and inflammatory reactions, smooth muscle cell proliferation, and angiogenesis. The beneficial and usually transient NF-kappaB-dependent gene expression may be exaggerated in pathological situations and results in damage to the vessel wall and impaired vascular cell function. In this review, we will capitalize on the favorable and adverse roles of NF-kappaB in the context of vascular disease, eg, chronic and localized inflammation, arteriosclerosis, and neoangiogenesis.
Subject(s)
Endothelium, Vascular/metabolism , Endothelium, Vascular/physiology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/physiology , NF-kappa B/physiology , Animals , Arteriosclerosis/metabolism , Arteriosclerosis/pathology , Endothelium, Vascular/cytology , Endothelium, Vascular/pathology , Gene Expression Regulation , Humans , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/pathology , NF-kappa B/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Physiologic/geneticsABSTRACT
Rho GTPases regulate diverse cellular functions including adhesion, cytokinesis and motility, as well as the activity of the transcription factors NF-kappaB, serum response factor and C/EBP. alpha-Catulin, an alpha-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 alpha-catulin also interacts with a key component of the NF-kappaB signalling pathway, namely the IkappaB kinase (IKK)-beta. In co-immunoprecipitations, alpha-catulin can bind IKK-beta and Lbc. Ectopic expression of alpha-catulin augmented NF-kappaB activity, promoted cell migration and increased resistance to apoptosis, whereas knockdown experiments showed the opposite effects. Together, these features suggest that alpha-catulin has tumorigenic potential.