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Cellular and viral components that mediate glucocorticoid-regulated processing of retroviral envelope proteins

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Conclusion

A comparison of the MMTV and MuLVenelope proteins in W7MG1 cells indicates that within the same cell some proteins are processed and sorted constitutively in the ER/Golgi system, whereas other proteins are processed in a hormone-dependent manner. The requisite hormone-dependent step in MMTV envelope protein processing occurs relatively early in the pathway, before the mannosidase II step (in the medial Golgi), which renders the oligosaccharide chains endo H resistant. Thus, the hormone dependent step must occur in the ER or early Golgi stacks; it cannot be proteolytic cleavage, any secondary glycosylation, sorting of proteins into specific secretory pathways (e.g., constitutive vs regulated), or transport to the cell surface, because all of these steps occur after acquisition of endo H resistance. The remaining candidates for the hormone-regulated step include core oligosaccharide trimming, subunit folding, subunit oligomerization (with homologous or heterologous proteins), or exit from the ER. Our current studies are focusing on these ER events.

The proteolytic cleavage step for the MMTV envelope proteins occurs after acquisition of endo H resistance and after terminal galactose addition (in thetrans-Golgi). Although studies of the envelope proteins of several other retroviruses have concluded that proteolytic cleavage occurs before acquisition of endo H resistance, we suggest that these conclusions are premature without examination of processing intermediates.

Finally, when the MMTV envelope gene is expressed in cells without any of the other MMTV genes, Pr74 is not processed to mature products. Although a point mutation in the envelope protein cannot be ruled out, we propose that the product of another MMTV gene may be required for the processing of Pr74.

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References

  1. Scammell, J. G., Burrage, T. G., and Dannies, P. S. (1986) Hormonal induction of secretory granules in a pituitary tumor cell llne.Endocrinology 119, 1543–1548.

    PubMed  CAS  Google Scholar 

  2. Blok, J., Gibbs, E. M., Lienhard, G. E., Slot, J. W., and Geuze, H. W. (1988) Insulininduced translocation of glucose transporters from post-Golgi compartments to the plasma membrane of 3T3-L1 adipocytes.J. Cell Biol. 106, 69–76.

    Article  PubMed  CAS  Google Scholar 

  3. Calderhead, D. M. and Lienhard, G. E. (1988) Labeling of glucose transporters at the cell surface in 3T3-L1 adipocytes.J. Biol. Chem. 263, 12,171–12,174.

    CAS  Google Scholar 

  4. Homer, H. C., Munck, A., and Lienhard, G. E. (1987) Dexamethasone causes translocation of glucose transporters from the plasma membrane to an intracellular site in human flbroblasts.J. Biol. Chem. 262, 17,696–17,702.

    Google Scholar 

  5. Chilton, B. S., Kaplan, H. A., and Lenuz, W. J. (1988) Estrogen regulation of the central enzymes involved in O-and N-linked glycoprotein assembly in the developing and adult rabbit endocervix.Endocrinology 123, 1237–1244.

    PubMed  CAS  Google Scholar 

  6. Wang, X., O’Hanlon, T. P., and Lau, J. T. Y. (1989) Regulation of β-galactoside-α-2,6-sialyl-transferase gene expression by dexamethone.J. Biol. Chem. 264, 1854–1859.

    PubMed  CAS  Google Scholar 

  7. Norvitch, M. E., Harvey, S., Smith, S., Hagstrom, J. E., and Wieben, E. D. (1989) Androgens affect the processing of secretory protein precursors in the guinea pig seminal vesicle. I. Evidence for androgen-regulated proteolytic processing.Mol. Endocrinol. 3, 1788–1796.

    Article  PubMed  CAS  Google Scholar 

  8. Rabindran, S. K., Danielsen, M., Firestone, G. L., and Stallcup, M. R. (1987) Glucocorticoid-dependent maturation of viral proteins in mouse lymphoma cells: Isolation of defective and hormone-independent cell variants.Som. Cell Mol Gen. 13, 131–143.

    Article  CAS  Google Scholar 

  9. Rabindran, S. K. and Stallcup, M. R. (1987) Mouse lymphoma cell variants with genetically dominant alteration in the maturation of viral glycoproteins.Mol. Endocrinol 1, 491–499.

    PubMed  CAS  Google Scholar 

  10. Byavan, S. and Stallcup, M. R. (1990) Glucocorlicoid-dependent maturation of mouse mammary tumor virus glycoproteins in mouse lymphoma cells: isolation of variants with constitutive viral protein maturation and normal glucocorticoid receptor function.Mol. Endocrinol. 4, 341–348.

    Google Scholar 

  11. Snider, L. D., Corey, J. L., Rabindran, S. K., and Stallcup, M. R. (1990) Characterization of oligosaccharide chains on mouse mammary tumor virus envelope proteins and the implications for the mechanism of their glucoccorticoid regulated processing.Mol. Endocrinol 4, 749–757.

    PubMed  CAS  Google Scholar 

  12. Corey, J. L. and Stallcup, M. R. (1990) The order of processing E.,ents in mouse mammary tumor virus envelope protein maturation: implications for the location of the glucocorticoid-regulated step.Cell Regulation 1, 531–541.

    PubMed  CAS  Google Scholar 

  13. Firestone, G. L., Payvar, F., and Yamamoto, K. R. (1982) Glucocorticoid regulation of protein processing and compartmentalization.Nature (Lond.) 300, 221–225.

    Article  CAS  Google Scholar 

  14. Danielsen, M., Peterson, D. O., and Stallcup, M. R. (1983) Immunological Selection of variant mouse lymphoid cells with altered glucocorticoid responsiveness.Mol. Cell Biol. 3, 1310–1316.

    PubMed  CAS  Google Scholar 

  15. Dickson, C. and Peters, G. (1983) Proteins encoded by mouse mammary tumor virus, inMouse Mammary Tumor Virus (Vogt, P. K. and Koprowski, H., eds.)Current Topics in Microbiology and Immunology; vol. 106, Springer-Verlag, Berlin, pp. 1–34.

    Google Scholar 

  16. Beato, M. (1989) Gene regulation by steroid hormones.Cell 56, 335–344.

    Article  PubMed  CAS  Google Scholar 

  17. Ham, J. and Parker, M. G. (1989) Regulation of gene expression by nuclear hormone receptors.Current Opinion in Cell Biology 1, 503–511.

    Article  PubMed  CAS  Google Scholar 

  18. Thompson, E. B., Tomkins, G. M., and Curran J. F. (1966) Induction of tyrosine α-ketoglutarate transaminase by steroid hormones in a newly established tissue culture line.Proc. Natl. Acad. Sci. USA 56, 296–303.

    Article  PubMed  CAS  Google Scholar 

  19. Ringold, G. M., Shank, P. R., Varmus, H. E., Ring, J., and Yamamoto K. R. (1979) Interaction and transcription of mouse mammary tumor virus DNA in rat hepatoma cells.Proc. Natl. Acad. Sct. USA 76, 665–669.

    Article  CAS  Google Scholar 

  20. Shackleford, G. M. and Varmus, H. E. (1988) Construction of a clonable, infectious, and tumorigenic mouse in tumor virus provirus and a derivative genetic vector.Proc. Natl. Acad. Sci. USA 85, 9655–9659.

    Article  PubMed  CAS  Google Scholar 

  21. Chen, C. and Okayama, H. (1987) High-deficiency transformation of mammalian cells by plasmid DNA.Mol Cell Biol. 7, 2745–2752.

    PubMed  CAS  Google Scholar 

  22. Ikuta, K. and Luftig, R. B. (1986) Inhibition of cleavage of Moloney murine leukemia virus gag andenv coded precursor polyproteins by cerulenin.Virology 154, 195–206.

    Article  PubMed  CAS  Google Scholar 

  23. Pfeffer, S. R. and Rothman, J. E. (1987) Biosynthetic protein transport and sorting by the endoplasmic reticulum and Golgi.Ann. Rev. Biochem. 56, 829–852.

    Article  PubMed  CAS  Google Scholar 

  24. Kornfeld, R. and Kornfeld, S. (1985) Assembly of asparagine-linked oligosaccharides.Ann. Rev. Biochem. 54, 631–664.

    Article  PubMed  CAS  Google Scholar 

  25. Lingappa, V. R. (1989) Intracellular traffic of newly synthesized proteins.J. Clin. Invest. 83, 739–751.

    Article  PubMed  CAS  Google Scholar 

  26. Plummer, T. H. (1984) Demonstration of peptide:N-glycosidase F activity in endobeta-N-acetylglucosarninidase F preparations.J. Biol. Chan. 259, 10,700–10,704.

    CAS  Google Scholar 

  27. Orci, L., Ravazzola, M., Storch, M. J., Anderson, R. G. W., Vassallt, J.-D., and Perrelet, A. (1987) Proteolytic maturation of insulin is a post-Golgi event which occurs in acidifying clathrin-coated secretory vesicles.Cell 49, 865–868.

    Article  PubMed  CAS  Google Scholar 

  28. Tsai, W.-P., and Oroszlan, S. (1988) Novel glycosylation pathways of retroviral envelope proteins identified with avian reticuloendotheliosis virus.J. Virol 62, 3167–3174.

    PubMed  CAS  Google Scholar 

  29. Stein, B. S. and Engleman, E. G. (1990) Intracellular processing of the gp l60 HIV-1 envelope precursor: endoproteolytic cleavage occurs in acis or medial compartment of the Golgi complex.J. Biol. Chem. 265, 2640–2649.

    PubMed  CAS  Google Scholar 

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Stallcup, M.R., Corey, J.L. & Bedgood, R.M. Cellular and viral components that mediate glucocorticoid-regulated processing of retroviral envelope proteins. Cell Biophysics 19, 93–108 (1991). https://doi.org/10.1007/BF02989883

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