Disease relevance of SVIL

• Consequently, semiquantitative analyses proved that the level of mRNA for SVIL and VEGF were significantly higher in P. gingivalis-LPS-stimulated neutrophils than in other bacterial (E. coli, Actinobacillus actinomycetemcomitans, Prevotella intermedia) LPS- or synthetic lipid A-stimulated neutrophils [1].
• Human supervillin mRNA is approximately 7.5 kb; this message is especially abundant in HeLa S3 cervical carcinoma, SW480 adenocarcinoma, and A549 lung carcinoma cell lines [2].
• Elevated mRNA expression for supervillin and vascular endothelial growth factor in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis [1].

High impact information on SVIL

• Supervillin modulation of focal adhesions involving TRIP6/ZRP-1 [3].
• TRIP6 partially rescues SV effects on stress fibers and FAs, apparently by mislocating SV away from FAs [3].
• Supervillin associates with androgen receptor and modulates its transcriptional activity [4].
• Together, our data demonstrate that SV is an AR coregulator that can enhance AR transactivation in muscle and other cells [4].
• Subcellular colocalization studies with fluorescence staining indicate SV can colocalize with AR in the presence of 5 alpha-dihydrotestosterone in COS-1 cells [4].

Biological context of SVIL

• Here, we report the cloning and characterization of supervillin (SV), a 205-kDa actin-binding protein, as an AR coregulator from the skeletal muscle cDNA library [4].
• We report here that supervillin, an F-actin binding protein originally isolated from bovine neutrophil plasma membranes, contains functional nuclear targeting signals and localizes at or near vinculin-containing focal adhesion plaques in COS7-2 and CV1 cells [5].
• These data suggest that archvillin is among the first costameric proteins to assemble during myogenesis and that it contributes to myogenic membrane structure and differentiation [6].
• Archvillin cDNAs also contain four exons that encode approximately 47 kDa of additional muscle-specific protein sequence in the form of two inserts within the function-rich N-terminus of supervillin [6].

Anatomical context of SVIL

• Our findings suggest that an elevated mRNA expression for SVIL could be associated with impaired function of neutrophils when stimulated by P. gingivalis-LPS [1].
• Domain analysis of supervillin, an F-actin bundling plasma membrane protein with functional nuclear localization signals [5].
• Overexpression of full-length supervillin in these cells disrupts the integrity of focal adhesion plaques and results in increased levels of F-actin and vinculin [5].
• Striking localizations of archvillin protein and mRNA were observed at the tips of differentiating myotubes [6].
• The membrane skeleton protein supervillin binds tightly to both F-actin and membranes and can potentiate androgen receptor activity in non-muscle cells [6].

Associations of SVIL with chemical compounds

• Mammalian two-hybrid and glutathione S-transferase pull-down assays indicate a domain within SV (amino acids 594-1268) can interact with AR N terminus and DNA-binding domain-ligand-binding domain in a ligand-enhanced manner [4].
• Human supervillin cDNAs cloned from normal human kidney and from the cervical carcinoma HeLa S3 predict a bipartite structure with three potential nuclear localization signals in the NH2-terminus and three potential actin-binding sequences in the COOH-terminus [2].
• Latrunculin B toxin, an actin chelator, reduces the availability of monomer actin and attenuates supervillin function [7].
• Supervillin, a membrane-associated, F-actin-binding protein, was identified as one of the testosterone downregulated genes in frontal DPCs [8].
• Recent studies indicate that supervillin, gelsolin and FliI are involved in intracellular signalling via nuclear hormone receptors including the androgen, oestrogen and thyroid hormone receptors [9].

Regulatory relationships of SVIL

• SV preferentially enhanced AR rather than other tested nuclear receptors and could be induced by natural androgens better than other steroids [4].

Other interactions of SVIL

• More recently, our lab has identified ARA267, a SET domain containing protein, and supervillin, an F-actin binding protein, as AR coregulators [10].
• In fact, throughout its length, the COOH-terminal half of supervillin is similar to segments 2-6 plus the COOH-terminal "headpiece" of villin, an actin-binding protein in intestinal microvilli [2].

References