ABC50, A NOVEL HUMAN ATP-BINDING CASSETTE PROTEIN FOUND IN TUMOR NECROSIS FACTOR-ALPHA-STIMULATED SYNOVIOCYTES

We have used the recently developed technique of differential display polymerase chain reaction to seek for new genes modulated by tumor nec rosis factor-alpha (TNF-alpha) in cultured synoviocytes. One PCR fragm ent was shown to correspond to a new gene that was mapped by high-reso lution fluorescence in situ hybridization to band 6p21.33. The cDNA of this gene was cloned, and the deduced amino acid sequence revealed co nsensus motifs for the nucleotide binding folds of the ATP-binding cas sette (ABC) family of proteins. However, a hydropathy curve showed tha t the polypeptide does not contain the transmembrane domains that are typical of the subfamily of ABC transporters and are associated with t ransporter/channel functions. The new gene, called ABC50, is the first human and mammalian ABC protein found to lack transmembrane domains. Homology with some yeast ABC proteins suggests that ABC50 codes for a new human ribosomal protein involved in translation of mRNA. It could therefore play a role in the enhancement of protein synthesis that fol lows TNF-alpha treatment of synoviocytes and thus participate in the i nflammatory processes mediated by this cytokine. Furthermore, since TN F-alpha also modulates the expression of MHC class I genes, and these genes are known to map to 6p21.33, it is hypothesized that ABC50 and M HC class I are part of the same chromatin expression domain. (C) 1998 Academic Press.