NITRILASE AND FHIT HOMOLOGS ARE ENCODED AS FUSION PROTEINS IN DROSOPHILA-MELANOGASTER AND CAENORHABDITIS-ELEGANS

The tumor suppressor gene FHIT encompasses the common human chromosoma l fragile site at 3p14.2 and numerous cancer cell biallelic deletions. To study Fhit function we cloned and characterized FHIT genes from Dr osophila melanogaster and Caenorhabditis elegans, Both genes code for fusion proteins in which the Fhit domain is fused with a novel domain showing homology to bacterial and plant nitrilases; the D. melanogaste r fusion protein exhibited diadenosine triphosphate (ApppA) hydrolase activity expected of an authentic Fhit homolog, In. human and mouse, t he nitrilase homologs and Fhit are encoded by two different genes: FHI T and NIT1, localized on chromosomes 3 and 1 in human, and 14 and 1 in mouse, respectively. We cloned and characterized human and murine NIT 1 genes and determined their exon-intron structure, patterns of expres sion, and alternative processing of their mRNAs. The tissue specificit y of expression of murine Fhit and Nit1 genes was nearly identical. Be cause fusion proteins with dual or triple enzymatic activities have be en found to carry out specific steps in a given biochemical or biosynt hetic pathway, we postulate that Fhit and Nit1 likewise collaborate in a biochemical or cellular pathway in mammalian cells.