Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway

Arthur M. Buchberg, Linda S. Cleveland, Nancy A. Jenkins, Neal G. Copeland

Research output: Contribution to journalArticle

169 Scopus citations

Abstract

NEUROFIBROMATOSIS type-1 (NF-1) is one of the most frequently inherited genetic disorders affecting humans1. NF-1 primarily affects cells of neural crest origin and is characterized by patches of skin pigmentation (café-au-lait spots) and neurofibromas2. Cloning of the human NF-1 gene shows that it encodes an 11-13 kilobase transcript that is frequently disrupted in NF-1 patients3-5. The frequent disruption of the NF-1 gene in NF-1 patients combined with the autosomal dominant mode of inheritance of NF-1 strongly suggest that the NF-1 gene is a tumour-suppressor gene. We have now sequenced a portion of the murine NF-1 gene and show that the predicted amino-acid sequence is nearly the same as the corresponding region of the human NF-1 gene product. Northern blotting identified mouse NF-1 transcripts that are equivalent in size and complexity to those in human tissues, and Southern blotting shows that this region of the NF-1 gene is evolutionarily well conserved. Finally, computer searches identified homology between the mouse NF-1 gene and IRA-1 and IRA-2, two genes identified in Saccharomyces cerevisiae that negatively regulate the RAS-cyclic AMP pathway. These findings provide important new insights into the possible function of the NF-1 gene.

Original languageEnglish (US)
Pages (from-to)291-294
Number of pages4
JournalNature
Volume347
Issue number6290
DOIs
StatePublished - Jan 1 1990

ASJC Scopus subject areas

  • General

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