CUTTING EDGE - TRANK, A NOVEL CYTOKINE THAT ACTIVATES NF-KAPPA-B AND C-JUN N-TERMINAL KINASE

We searched the expressed sequence tag database using sequence homolog y and identified a novel cytokine, which we have named TRANK (thioredo xin peroxidase-related activator of NF-kappa B and c-Jun N-terminal ki nase), The predicted amino acid sequence of TRANK was highly homologou s to that of the thiol-specific antioxidant proteins. Unlike these pro teins, however, TRANK had a putative secretory signal polypeptide and was found to be secreted by cells. TRANK was expressed in most tissues and cell lines, and the gene that encodes it was mapped to chromosome Xp21-22,1, TRANK activated NF-kappa B and induced the degradation of the inhibitory subunit of NF-kappa B, In addition, TRANK upregulated t he expression of NF-kappa B-dependent gene products, ICAM-1, and induc ible nitric oxide synthase, TRANK also activated c-Jun N-terminal kina se and induced the proliferation of normal human foreskin fibroblasts. Its homology with antioxidant proteins, wide distribution in tissues, and ability to activate NF-kappa B and c-Jun N-terminal kinase sugges t that TRANK plays an important role in inflammation.