Disease relevance of AVIL

• Genomic structure, chromosome mapping and expression analysis of the human AVIL gene, and its exclusion as a candidate for locus for inflammatory bowel disease at 12q13-14 (IBD2) [1].
• Interestingly, the location of one of the RNA-binding domains in p92 is similar to the RNA-binding domain of the NS5B RdRp protein of hepatitis C virus [2].
• We observed a decrease in the proliferation rate in cells from normal skin (39%), hypertrophic scar (44%), keloid (63%) and in DNA synthesis in cells from normal skin (50%), hypertrophic scar (55%) and keloid (63%) treated with 8 mM avil (72 h) [3].

High impact information on AVIL

• Using a yeast two-hybrid screen and cotransfection experiments with Cos-1 cells, evidence was adduced that p92 is HPK-1, a serine/threonine-specific protein kinase expressed in hemopoietic cells [4].
• In contrast, it became complexed in activated T cells and myeloid cells with an as yet unknown tyrosine-phosphorylated polypeptide of approximately 92 kDa (p92) [4].
• Phase-specific inhibitors, therefore, are responsible for the cell cycle dependence of p92 activity and provide a novel mechanism linking transcription factor regulation with the cell cycle [5].
• The human papillomavirus type 18 p92 binding sequence confers enhancer activity on a heterologous promoter, suggesting that p92 acts as a transcription factor [5].
• The nuclear factor p92, originally discovered by its interaction with the human papillomavirus type 18 enhancer, is a cellular protein whose activity is restricted to S phase in human primary fibroblasts [5].

Biological context of AVIL

• We have determined the genomic organization of the AVIL gene, including the transcription start site and its localization with respect to D12S83 [1].
• The 2457 bp coding region of AVIL consists of 19 exons and is localized to 12q14 proximal to D12S83 [1].
• We have evaluated AVIL as a candidate susceptibility gene for IBD2 in 24 unrelated patients with evidence of linkage to chromosome 12, as well as in 91 individuals from 19 affected IBD families for putative single nucleotide polymorphisms [1].
• AVIL encodes a protein (advillin) which belongs to the gelsolin/villin family of proteins and might therefore be involved in morphogenesis of microvilli [1].
• In addition, tyrosine phosphorylation of p92 was dependent on engagement of Mac-1 with ligand [6].

Anatomical context of AVIL

• We propose that p92 (advillin) has unique functions in the morphogenesis of neuronal cells which form ganglia, and that it may compensate to explain the near normal phenotype observed in villin-deficient mice [7].
• In serum starved Hela-fibroblast hybrid cells p92 is localized to the cytosol [8].
• Virtually all Par o 1-specific T cell lines and large numbers of Par o 1-specific T cell clones proliferated in response to two Par o 1 nonapeptides (p92 and p96), which probably contain immunodominant epitopes of the Par o 1 allergen [9].
• We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase [10].

Associations of AVIL with chemical compounds

• Integrin-stimulated phosphorylation of p92 created binding sites that were recognized in vitro by the SH2 domains of c-CrkII and Src [6].
• Forty-two percent of TAM users versus 32% of AI users took Advil (Wyeth, Richmond, VA) for muscle/joint aches; 47.5% of AI users switched medication to improve symptoms as compared with only 37% of tamoxifen users (P = .015) [11].
• The proprietary formulations chosen for study were Phensedyl linctus, Avil tablets and Ponderax tablets [12].
• In order to find a therapeutic control for scar formation, we investigated the effect of avil (pheniramine maleate) on fibroblasts cultured from abnormal scars in comparison to normal skin [3].

Regulatory relationships of AVIL

• Several observations suggest that this event may be an important step in the signaling pathway initiated by Mac-1 binding. p92 phosphorylation was specifically blocked with antibodies to CD11b, the alpha-subunit of Mac-1, and was rapidly reversible on disengagement of the integrin ligand interaction [6].

Other interactions of AVIL

• A candidate susceptibility gene for IBD2 in this region is the AVIL gene [1].
• We report the three-dimensional solution structures of the C-terminal headpiece subdomains of human villin (HVcHP) and human advillin (HAcHP), determined by two-dimensional 1H-NMR [13].
• Phosphorylation of p92 was inducible when Mac-1 was activated by phorbol 12-myristate 13-acetate, the beta(2)-specific activating antibody CBR LFA-1/2, or interleukin-8 (77 amino acids) [6].

References