Transformation suppressor genes.
Flat revertants with reduced malignancy in vivo can be isolated from Kirsten sarcoma virus-transformed NIH3T3 cells following transfection with a normal human fibroblast cDNA expression library. We have recovered from one such revertant a 1.8 kb cDNA clone, "Krev-1", that possesses revertant-inducing activity in transfection assay. The Krev-1 cDNA has the capacity to encode a protein with a calculated molecular weight of 21,000 having strong structural similarity to ras proteins (ca. 50% homology), especially in their GTP/GDP-binding, effector-binding and membrane attachment domains. Point-mutations of Krev-1 protein at the 12th and the 59th amino acid positions from the aminoterminus potentiated the transformation suppressor activity by 2-5 times, and point-mutations within the putative effector-binding domain and at the C-terminal acylation site reduced the activity.
Noda
M
M
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Kitayama
H
H
Kanazawa
S
S
Murata
S
S
Matsuzaki
T
T
Ikawa
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D003260:Contact Inhibition; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D006801:Humans; D007708:Kirsten murine sarcoma virus; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015689:Oncogene Protein p21(ras) / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D020668:rap GTP-Binding Proteins
D004247:DNA; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras); D020668:rap GTP-Binding Proteins