Hyperactive Ras as a therapeutic target in neurofibromatosis type 1

Am J Med Genet. 1999 Mar 26;89(1):14-22.


The NF1 gene encodes neurofibromin, a GTPase-activating protein (GAP) for members of the p21(ras) (Ras) family, which negatively regulates Ras output by accelerating the conversion of active Ras. GTP to inactive Ras.GDP. Analysis of tumors from patients with neurofibromatosis type 1 (NF1) has shown biochemical evidence of hyperactive Ras as well as frequent loss of the normal NF1 allele, consistent with its role as a tumor suppressor gene. Taken together, these data suggest that novel therapeutics directed against components of the Ras signaling cascade might provide effective treatments for certain pathological complications of NF1. Here we summarize data that support a role for hyperactive Ras in NF1 disease, including Ras processing, activation, and down-regulation. We review targets for rational drug design, provide preliminary results, and discuss implications for future studies. Am. J. Med. Genet. (Semin. Med. Genet.) 89:14-22, 1999.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Drug Design
  • GTPase-Activating Proteins
  • Genes, Neurofibromatosis 1*
  • Humans
  • Neurofibromatosis 1 / genetics*
  • Neurofibromatosis 1 / therapy*
  • Proteins / genetics*
  • Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Sequence Deletion
  • Signal Transduction
  • ras GTPase-Activating Proteins
  • ras Proteins / genetics
  • ras Proteins / metabolism


  • GTPase-Activating Proteins
  • Proteins
  • ras GTPase-Activating Proteins
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins