Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product

The transforming gene (src) of avian sarcoma virus (ASV) and adjacent regions of the viral genome have been isolated by molecular cloning of viral DNA. Their nucleotide sequence encompasses the whole of src and the portion of the gene env that encodes gp 37, one of two glycoproteins found in the viral envelope. Src encodes a single, hydrophobic protein with structural features that conform to previous descriptions of the gene product (pp60src). It appears that a single viral protein is responsible for both the initiation and maintenance of neoplastic transformation by avian sarcoma virus. Neither src nor its product bear any obvious structural relationship to several other viral oncogenes and their encoded proteins. Src is flanked by a repeated nucleotide sequence that may facilitate frequent deletion of the gene from the viral genome.

[1]  D. Lowy,et al.  Molecular cloning of the Harvey sarcoma virus closed circular DNA intermediates: initial structural and biological characterization , 1979, Journal of virology.

[2]  R. Erikson,et al.  Avian sarcoma virus-transforming protein, pp60src shows protein kinase activity specific for tyrosine , 1980, Nature.

[3]  Tony Hunter,et al.  Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus , 1980, Cell.

[4]  C C Bigelow,et al.  On the average hydrophobicity of proteins and the relation between it and protein structure. , 1967, Journal of theoretical biology.

[5]  J. Brugge,et al.  Identification of a transformation-specific antigen induced by an avian sarcoma virus , 1977, Nature.

[6]  A. Levinson,et al.  The protein encoded by the transforming gene of avian sarcoma virus (pp60src) and a homologous protein in normal cells (pp60proto-src) are associated with the plasma membrane. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[7]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[8]  L. Wang.  The gene order of avian RNA tumor viruses derived from biochemical analyses of deletion mutants and viral recombinants. , 1978, Annual review of microbiology.

[9]  H. Varmus,et al.  Virus-specific DNA in the cytoplasm of avian sarcoma virus-infected cells is a precursor to covalently closed circular viral DNA in the nucleus , 1978, Journal of virology.

[10]  H. Varmus,et al.  At least 104 nucleotides are transposed from the 5′ terminus of the avian sarcoma virus genome to the 5′ termini of smaller viral mrnas , 1978, Cell.

[11]  T. Hunter,et al.  Characterization of Rous sarcoma virus src gene products synthesized in vitro , 1978, Journal of virology.

[12]  J. M. Buchanan,et al.  Processing of 60,000-dalton sarc gene protein synthesized by cell-free translation. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[13]  W. Gilbert,et al.  A new method for sequencing DNA. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Varmus,et al.  The size and genetic composition of virus-specific RNAs in the cytoplasm of cells producing avian sarcoma-leukosis viruses , 1977, Cell.

[15]  J. Taylor,et al.  Analysis of unintegrated avian RNA tumor virus double-stranded DNA intermediates , 1978, Journal of virology.

[16]  J. Coffin.  Structure, replication, and recombination of retrovirus genomes: some unifying hypotheses. , 1979, The Journal of general virology.

[17]  R. Montelaro,et al.  An analysis of type-C retrovirus polypeptides and their associations in the virion. , 1978, Virology.

[18]  G. Khoury,et al.  BKV splice sequences based on analysis of preferred donor and acceptor sites. , 1979, Nucleic acids research.

[19]  H. Hanafusa,et al.  Recombination between viral and cellular sequences generates transforming sarcoma virus. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[20]  H. Varmus,et al.  Kinetics of synthesis, structure and purification of avian sarcoma virus-specific DNA made in the cytoplasm of acutely infected cells. , 1978, Journal of molecular biology.

[21]  R. Weinberg,et al.  Structure of the intermediates leading to the integrated provirus. , 1977, Biochimica et biophysica acta.

[22]  I. Pastan,et al.  Localization of the ASV src gene product to the plasma membrane of transformed cells by electron microscopic immunocytochemistry , 1979, Cell.

[23]  J. M. Bishop,et al.  The nucleotide sequence of an untranslated but conserved domain at the 3' end of the avian sarcoma virus genome , 1980, Nucleic Acids Res..

[24]  G. Klein.  Lymphoma development in mice and humans: diversity of initiation is followed by convergent cytogenetic evolution. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[25]  H. Varmus,et al.  Heterogeneity of genetic loci in chickens: analysis of endogenous viral and nonviral genes by cleavage of DNA with restriction endonucleases , 1979, Cell.

[26]  T. Hunter,et al.  Transforming gene product of Rous sarcoma virus phosphorylates tyrosine , 1980, Proceedings of the National Academy of Sciences.

[27]  P. A. Biro,et al.  Ubiquitous, interspersed repeated sequences in mammalian genomes. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[28]  H. Varmus,et al.  Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein , 1978, Cell.

[29]  B. Mahy.  The molecular biology of tumor viruses: edited by John Tooze. Pp. 743. (Cold Spring Harbor Laboratory: New York). $16.00 , 1974 .

[30]  E. Krebs,et al.  Phosphorylation-dephosphorylation of enzymes. , 1979, Annual review of biochemistry.

[31]  J. Messing,et al.  Methylation of single-stranded DNA in vitro introduces new restriction endonuclease cleavage sites , 1978, Nature.

[32]  J. Brugge,et al.  A normal cell protein similar in structure and function to the avian sarcoma virus transforming gene product. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Steitz,et al.  Conservation of the primary structure at the 3′ end of 18S rRNA from eucaryotic cells , 1978, Cell.

[34]  H. Varmus,et al.  Mapping unintegrated avian sarcoma virus DNA: Termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA , 1978, Cell.

[35]  R. Erikson,et al.  Structural analysis of the avian sarcoma virus transforming protein: sites of phosphorylation , 1979, Journal of virology.

[36]  P. Y. Chou,et al.  Prediction of protein conformation. , 1974, Biochemistry.

[37]  R. Eisenman,et al.  The biosynthesis of oncovirus proteins. , 1978, Biochimica et biophysica acta.

[38]  L. Hood,et al.  New protein sequenator with increased sensitivity. , 1980, Science.

[39]  A. Zelenetz,et al.  Transformation by subgenomic fragments of Rous sarcoma virus DNA , 1980, Cell.

[40]  W. Wickner.  The assembly of proteins into biological membranes: The membrane trigger hypothesis. , 1979, Annual review of biochemistry.

[41]  P. Duesberg,et al.  Subgenomic, cellular Rous sarcoma virus RNAs contain oligonucleotides from the 3′ half and the 5′ terminus of virion RNA , 1977, Nature.

[42]  J. Coffin,et al.  Recombinants between endogenous and exogenous avian tumor viruses: role of the C region and other portions of the genome in the control of replication and transformation , 1980, Journal of virology.