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

Yuri Pekarsky, Manuela Campiglio, Zurab Siprashvili, Teresa Druck, Yurii Sedkov, Sergei Tillib, Alexandra Draganescu, Peter Wermuth, Joel H. Rothman, Kay Huebner, Arthur M. Buchberg, Alexander Mazo, Charles Brenner, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

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 exonintron 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.

Original languageEnglish
Pages (from-to)8744-8749
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number15
DOIs
Publication statusPublished - Jul 21 1998

ASJC Scopus subject areas

  • Genetics
  • General

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