Submitted to: Plant and Animal Genome Conference
Publication Type: Abstract only
Publication Acceptance Date: 11/13/2004
Publication Date: 1/15/2005
Citation: Connor, E.E., Szperka, M.E., Paape, M.J., Williams, J.L., Bannerman, D.D. 2005. Functional characterization of bovine flice-like inhibitory protein (flip): identification of a protective role against inflammatory mediator-induced apoptosis and nf-kb activation [abstract]. Plant and Animal Genome Conference XIII. p. 533. Interpretive Summary: THIS IS AN ABSTRACT ONLY. NO INTERPRETIVE SUMMARY REQUIRED.
Technical Abstract: In humans and mice, FLICE-like inhibitory protein (FLIP) inhibits apoptosis and induction of NF-kB by pro-inflammatory mediators. These processes are critical events in the pathogenesis of a variety of diseases in cattle, including mastitis. Because of its importance in moderating apoptosis and NF-kB activation in other species, the bovine FLIP gene was mapped, its cDNA sequenced and its expression characterized in cultured primary bovine endothelial cells. Sequencing of bovine FLIP cDNA revealed 83, 74 and 68% amino acid sequence identity to porcine, human and murine FLIP proteins, respectively. Bovine FLIP was positioned on chromosome 2 (BTA2) nearest marker BMS2626 using radiation hybrid mapping. This region of BTA2 corresponds to a quantitative trait locus for functional herd life in dairy cattle, suggesting FLIP as a positional candidate gene contributing to this longevity trait. In addition, functional studies showed over-expression of bovine FLIP prevents bacterial lipopolysaccharide (LPS)- and TNF-a-induced apoptosis in bovine endothelial cells, consistent with previous studies of human FLIP. Only full-length bovine FLIP protein could inhibit NF-kB activation induced by LPS, whereas the death effector domain of the protein alone was capable of inhibiting TNF-a-induced NF-kB activation. These results support the conservation of FLIP function across species.