Association of Krev-1/rap1a With Krit1, a Novel Ankyrin Repeat-Containing Protein Encoded by a Gene Mapping to 7q21-22

Oncogene. 1997 Aug 28;15(9):1043-9. doi: 10.1038/sj.onc.1201268.

Abstract

Krev-1/rap1A is an evolutionarily conserved Ras-family GTPase whose cellular function remains unclear, but which has been proposed to function as a tumor suppressor gene, and may act as a Ras antagonist. To elucidate Krev-1 activity, we have used LexA-Krev-1 in a two-hybrid screen of a HeLa cell cDNA library. Of the two cDNA classes isolated, one contained a single isolate encoding the known Krev-1 interactor Raf, while the second contained multiple isolates coding for a previously undescribed protein which we have designated Kritl (for Krev Interaction Trapped 1). The full length Krit1 cDNA encodes a protein of 529 amino acids, with an amino-terminal ankyrin repeat domain and a novel carboxy-terminal domain required for association with Krit1. Krit1 interacted strongly with Krev-1 but only weakly with Ras, suggesting it might specifically regulate Krev-1 activities. Krit1 mRNA and protein are expressed endogenously at low levels, with tissue specific variation. Intriguingly, the Krit cDNA has been mapped by FISH to chromosome 7q21-22, a region known to be frequently deleted or amplified in multiple forms of cancer.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Ankyrin Repeat*
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7*
  • Cloning, Molecular
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • KRIT1 Protein
  • Microtubule-Associated Proteins*
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / isolation & purification
  • Proto-Oncogene Proteins / metabolism*
  • rap GTP-Binding Proteins

Substances

  • KRIT1 Protein
  • KRIT1 protein, human
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins
  • GTP-Binding Proteins
  • rap GTP-Binding Proteins

Associated data

  • GENBANK/U90269