Molecular Cloning, Phylogenetic Analysis, Tissue Distribution, and Expression of the Cytokine TWEAK in Zebrafish (Danio rerio)

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK; also known as Apo3L, TNFSF12, CD255) is a member of the TNF superfamilies (Wiley and Winkles 2003; Winkles 2008). TWEAK is a homotrimer that is found either on the cell surface as a type II transmembrane protein or is released in soluble form after being cleaved by a furin-like protease (Chicheportiche et al. 1997). Its cognate receptor is fibroblast growth factor-inducible 14 (Fn14; also known as TWEAKR, TNFRSF12A, CD266). TWEAK and Fn14 interact in multiple biological responses, including stimulation of proliferation, migration, apoptosis, angiogenesis, and induction of proinflammatory cytokines (Winkles 2008; Blanco-Colio et al. 2007; Yepes and Winkles 2006; Yepes 2007). TWEAK is involved in important biological effects, including up-regulating proinflammatory chemokines, cytokines, and adhesion molecules; inducing cell death and apoptosis; and enhancing cell survival. TWEAK promotes angiogenesis by increasing survival, proliferation, and migration of endothelial cells (Lynch et al. 1999). Conversely, TWEAK has also been shown to promote various types of cell death. Depending on the cell type, TWEAK induces