Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans.

TitleNitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans.
Publication TypeJournal Article
Year of Publication1998
AuthorsPekarsky Y, Campiglio M, Siprashvili Z, Druck T, Sedkov Y, Tillib S, Draganescu A, Wermuth P, Rothman JH, Huebner K, Buchberg AM, Mazo A, Brenner C, Croce CM
JournalProc Natl Acad Sci U S A
Volume95
Issue15
Pagination8744-9
Date Published1998 Jul 21
ISSN0027-8424
KeywordsAcid Anhydride Hydrolases, Alternative Splicing, Amino Acid Sequence, Aminohydrolases, Animals, Base Sequence, Caenorhabditis elegans, Cloning, Molecular, DNA, Complementary, Drosophila melanogaster, Humans, Mice, Molecular Sequence Data, Neoplasm Proteins, Proteins, Recombinant Fusion Proteins, Sequence Homology, Amino Acid
Abstract

The tumor suppressor gene FHIT encompasses the common human chromosomal fragile site at 3p14.2 and numerous cancer cell biallelic deletions. To study Fhit function we cloned and characterized FHIT genes from Drosophila 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. melanogaster fusion protein exhibited diadenosine triphosphate (ApppA) hydrolase activity expected of an authentic Fhit homolog. In human and mouse, the nitrilase homologs and Fhit are encoded by two different genes: FHIT and NIT1, localized on chromosomes 3 and 1 in human, and 14 and 1 in mouse, respectively. We cloned and characterized human and murine NIT1 genes and determined their exon-intron structure, patterns of expression, and alternative processing of their mRNAs. The tissue specificity of expression of murine Fhit and Nit1 genes was nearly identical. Because fusion proteins with dual or triple enzymatic activities have been found to carry out specific steps in a given biochemical or biosynthetic pathway, we postulate that Fhit and Nit1 likewise collaborate in a biochemical or cellular pathway in mammalian cells.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID9671749
PubMed Central IDPMC21147
Grant ListCA21124 / CA / NCI NIH HHS / United States
CA39880 / CA / NCI NIH HHS / United States
CA51083 / CA / NCI NIH HHS / United States
R01 CA075954 / CA / NCI NIH HHS / United States
R01 CA075954-03 / CA / NCI NIH HHS / United States