rsc: a novel oncogene with structural and functional homology with the gene family of exchange factors for Ral.
A novel oncogene, rsc (rabbit squamous cell carcinoma), has been identified from a DMBA-induced rabbit squamous cell carcinoma using gene transfer and the nude mouse tumorigenesis assay. A full-length cDNA has been isolated and sequenced. rsc has potent tumorigenic activity in nude mice (latency <4 weeks), but does not induce focus formation or anchorage independent growth. The oncogene resulted from the fusion of rHR 23A (a rabbit homologue of yeast Rad 23) with a member of the ral-GDS family which we named rgr (ral-GDS related). Deletion analysis demonstrated that the oncogenic potential resides in the Rgr portion of the gene. Rgr is 40% identical overall to Ral-GDS, with identity increasing to 72% over a 100 amino acid region of the catalytic domain. Biochemical experiments indicate that Rgr has GTP/GDP exchange activity for Ral, providing evidence that this pathway is associated with tumorigenesis. The linkage between the Ral pathway and tumorigenesis by a molecule in the Ral-GDS gene family (Ral-GDS being a known effector for Ras) will open the way for the characterization of this pathway and provide an important tool to understand its biological function.
D'Adamo
D R
DR
Department of Pathology and Kaplan Cancer Center, New York University Medical Center, New York 10016, USA.
Novick
S
S
Kahn
J M
JM
Leonardi
P
P
Pellicer
A
A
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics; D002461:Cell Line, Transformed; D018076:DNA, Complementary; D005136:Eye Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D017386:Sequence Homology, Amino Acid; D020725:ral GTP-Binding Proteins; D020666:ras-GRF1
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D005136:Eye Proteins; C089754:G protein-coupled receptor RGR; D015513:Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D020666:ras-GRF1; C106555:rsc protein, Oryctolagus cuniculus; D010749:Phosphoprotein Phosphatases; D019204:GTP-Binding Proteins; D020725:ral GTP-Binding Proteins