D. Young

Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains.

We have cloned and sequenced a new human oncogene and have named it mas. This oncogene was detected by its tumorigenicity in nude mice using the cotransfection and tumorigenicity assay previously described. The mas oncogene has a weak focus-inducing activity in transfected NIH 3T3 cells. A DNA rearrangement in the 5 noncoding sequence, which occurred during transfection, is probably responsible for activation of the mas gene. The cDNA sequence of the mas oncogene reveals a long open reading frame that codes for a 325 amino acid protein. This protein is very hydrophobic and has seven potential transmembrane domains. In this respect, the structure of the mas protein is novel among cellular oncogene products and may reflect a new functional class of oncogenes.

Mutational mapping of RAS-responsive domains of the Saccharomyces cerevisiae adenylyl cyclase.

Large deletion and small insertion mutations in the adenylyl cyclase gene of Saccharomyces cerevisiae were used to map regions required for activation by RAS protein in vitro. The amino-terminal 605 amino acids were found to be dispensable for responsiveness to RAS protein. All other deletions in adenylyl cyclase destroyed its ability to respond to RAS. Small insertion mutations within the leucine-rich repeat region also prevented RAS responsiveness, while other insertions did not.

The adenylyl cyclase-encoding gene from Saccharomyces kluyveri

The gene encoding adenylyl cyclase (CYR) from Saccharomyces kluyveri has been cloned. Comparison of the predicted amino acid sequence of this protein with the Schizosaccharomyces pombe and Saccharomyces cerevisiae CYRs revealed homology between different structural and putative functional domains that suggest a high degree of conservation in the function and regulation of these proteins.

Characterization of Two New Human Oncogenes

The first oncogenes discovered were the transforming genes of the oncogenic viruses (reviewed by Bishop 1985). The subsequent discovery that the oncogenes of retroviruses were derived from normal host cellular genes provided the first direct evidence that cellular genomes contain genes with transforming potential. More recently, the development of techniques for DNA transfer in eukaryotic cells led to the discovery of cellular transforming genes in tumor cells by their ability to induce foci of transformed NIH-3T3 cells (reviewed by Land et al. 1983). Several new oncogenes have been discovered this way, including N-ras (Shimizu et al. 1983), met (Cooper et al. 1984), neu (Bargmann et al. 1986), and possible others (Goubin et al. 1983; Lane et al. 1984; Takahashi et al. 1985).