Abstract
Using Xenopus eggs and NIH3T3 cells as assay systems, we have compared the physiological (i.e. maturation–inducing and cleavage–arresting) and in vitro transforming activities of the c–mos genes from various species as well as their mutant genes. These analyses show that the three biological activities all depend upon the intrinsic protein kinase activity of Mos and correlate well with each other. Furthermore, our results demonstrate that a well conserved N–terminal 14–amino acid sequence of Mos, termed the Mos–hox, is essential for all three activities. These results indicate that the in vitro transforming activity of Mos can he ascribed to the same kinase activity of Mos that exerts the physiological activities.
Keywords: c‐mos– Proto–oncogene, Physiological activity, Transforming activity –domain structure
Full Text
The Full Text of this article is available as a PDF (272.2 KB).
REFERENCES
- 1. ) Watanabe , N. , Vande Woude , G. F. , Ikawa , Y. and Sagata , N , Specific proteolysis of the c–mos protooncogene product by calpain on fertilization of Xenopus eggs . Nature , 342 , 505 – 511 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Propst , F. and Vande Woude , G. F.Expression of c–mos proto–oncogene transcripts in mouse tissues . Nature , 315 , 516 – 518 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Goldman , D. S. , Kiessling , A. A. , Millette , C. F. and Cooper , G. M.Expression of c–mos RNA in germ cells of male and female mice . Proc. Natl. Acad. Sci. USA , 84 , 4509 – 4513 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. ) Keshet , E. , Rosenberg , M. P. , Mercer , J. A. , Propst , F. , Vande Woude , G. F. , Jenkins , N. A. and Copeland , N. G.Developmental regulation of ovarian–specific Mos expression . Oncogene , 2 , 235 – 240 ( 1988. ). [PubMed] [Google Scholar]
- 5. ) Paules , R. S. , Buccione , R. , Moschel , R. C. , Vande Woude , G. F. and Eppig , J. J.Mouse Mos protooncogene product is present and functions during oogenesis . Proc. Natl. Acad. Sci. USA , 86 , 5395 – 5399 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. ) O'Keefe , S. J. , Wolfes , H. , Kiessling , A. A. and Cooper , G. M.Microinjection of antisense c–mos oligonucleotides prevents meiosis II in the maturing mouse egg . Proc. Natl. Acad. Sci. USA , 86 , 7038 – 7042 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. ) Sagata , N. , Oskarsson , M. , Copeland , T. , Brumbaugh , J. and Vande Woude , G. F.Function of c–mos protooncogene product in meiotic maturation in Xenopus oocytes . Nature , 335 , 519 – 525 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Sagata , N. , Daar , I. , Oskarsson , M. , Showalter , S. D. and Vande Woude , G. F.The product of the mos protooncogene as a candidate “initiator” for oocyte maturation . Science , 245 , 643 – 646 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Freeman , R. S. , Pickham , K. M. , Kanki , J. P. , Lee , B. A. , Pena , S. V. and Donoghue , D. J.Xenopus homolog of the mos protooncogene transforms mammalian fibroblasts and induces maturation of Xenopus oocytes . Proc. Natl. Acad. Sci. USA , 86 , 5805 – 5809 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Masui , Y. and Markert , C. L.Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes . J. Exp. Zool. , 177 , 129 – 146 ( 1971. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Sagata , N. , Watanabe , N. , Vande Woude , G. F. and Ikawa , Y.The c–mos proto–oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs . Nature , 342 , 512 – 519 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Blair , D. G. , Oskarsson , M. K. , Seth , A. , Dunn , K. J. , Dean , M. , Zweig , M. , Tainsky , M. A. and Vande Woude , G. F.Analysis of the transforming potential of the human homolog of mos . Cell , 46 , 785 – 794 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Graham , F. L. and van der Eb , A. J.A new technique for the assay of infectivity of human adenovirus 5 DNA . Virology , 52 , 456 – 467 ( 1973. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Roitt , L , Brostoff , J. and Male , D. “ Immunology ”, Chap. 15 , pp. 4 – 5 ( 1985. ). Gower Medical Publishing; , London , New York . [Google Scholar]
- 15. ) Nishitani , H. , Kobayashi , H. , Ohtsubo , M. and Nishimoto , T.Cloning of Xenopus RCC1 cDNA, a homolog of the human RCC1 gene: complementation of tsBN2 mutation and identification of the product . J. Biochem. , 107 , 228 – 235 ( 1990. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Oskarsson , M. , McClements , W. L. , Blair , D. G. , Maizel , J. V. and Vande Woude , G. F.Properties of normal mouse cell DNA sequence (sarc) homologous to the src sequence of Moloney sarcoma virus . Science , 207 , 1222 – 1224 ( 1980. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Taylor , J. W. , Ott , J. and Eckstein , F.The rapid generation of oligonucleotide–directed mutations at high frequency using phosphorothioate–modified DNA . Nucleic Acids Res. , 13 , 8764 – 8785 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. ) Hannink , M. and Donoghue , D. J.Lysine residue 121 in the proposed ATP–binding site of the v–mos protein is required for transformation . Proc. Natl. Acad. Sci. USA , 82 , 7894 – 7898 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]