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. 1985 Nov;5(11):3297–3300. doi: 10.1128/mcb.5.11.3297

An adenovirus 2-coded tumor antigen located on the endoplasmic reticulum and nuclear envelope is required for growth of transformed cells in Ca2+-deficient media.

T Subramanian, M Kuppuswamy, G Chinnadurai
PMCID: PMC369148  PMID: 3018514

Abstract

Rat embryo cell lines containing the adenovirus 2 E1a region together with normal or mutant forms of the N-terminal half of the E1b region (HindIII G fragment) were generated by using a dominant selection marker, neo. Biochemically transformed cells containing a nonmutated HindIII G fragment proliferated more rapidly in Ca2+-deficient media, whereas cells containing a specific deletion within the E1b-encoded, 175-amino-acid (175R) (19-kilodalton) T-antigen gene and nontransformed cells grew at a slower rate. Furthermore, transformed cells that did not express the 175R T antigen and untransformed cells could not replicate their DNA efficiently in low-Ca2+ medium. Our results suggest that Ca2+ ions may provide an important stimulus for cell proliferation in adenovirus-transformed cells through a mechanism that involves the functions of the 175R T antigen.

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Selected References

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  1. Babiss L. E., Fisher P. B., Ginsberg H. S. Effect on transformation of mutations in the early region 1b-encoded 21- and 55-kilodalton proteins of adenovirus 5. J Virol. 1984 Nov;52(2):389–395. doi: 10.1128/jvi.52.2.389-395.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berridge M. J. Inositol trisphosphate and diacylglycerol as second messengers. Biochem J. 1984 Jun 1;220(2):345–360. doi: 10.1042/bj2200345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  4. Chinnadurai G. Adenovirus 2 Ip+ locus codes for a 19 kd tumor antigen that plays an essential role in cell transformation. Cell. 1983 Jul;33(3):759–766. doi: 10.1016/0092-8674(83)90018-1. [DOI] [PubMed] [Google Scholar]
  5. Colbère-Garapin F., Horodniceanu F., Kourilsky P., Garapin A. C. A new dominant hybrid selective marker for higher eukaryotic cells. J Mol Biol. 1981 Jul 25;150(1):1–14. doi: 10.1016/0022-2836(81)90321-1. [DOI] [PubMed] [Google Scholar]
  6. Durham A. C., Walton J. M. Calcium ions and the control of proliferation in normal and cancer cells. Biosci Rep. 1982 Jan;2(1):15–30. doi: 10.1007/BF01142195. [DOI] [PubMed] [Google Scholar]
  7. Durkin J. P., Boynton A. L., Whitfield J. F. The src gene product (pp60 src) of avian sarcoma virus rapidly induces DNA synthesis and proliferation of calcium-deprived rat cells. Biochem Biophys Res Commun. 1981 Nov 16;103(1):233–239. doi: 10.1016/0006-291x(81)91684-3. [DOI] [PubMed] [Google Scholar]
  8. Fisher P. B., Babiss L. E., Weinstein I. B., Ginsberg H. S. Analysis of type 5 adenovirus transformation with a cloned rat embryo cell line (CREF). Proc Natl Acad Sci U S A. 1982 Jun;79(11):3527–3531. doi: 10.1073/pnas.79.11.3527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freeman A. E., Hollinger S., Price P. J., Calisher C. The effect of calcium on cell lines derived from adenovirus type 12-induced hamster tumors. Exp Cell Res. 1965 Aug;39(1):259–264. doi: 10.1016/0014-4827(65)90028-5. [DOI] [PubMed] [Google Scholar]
  10. Fukui Y., Saito I., Shiroki K., Shimojo H. Isolation of transformation-defective, replication-nondefective early region 1B mutants of adenovirus 12. J Virol. 1984 Jan;49(1):154–161. doi: 10.1128/jvi.49.1.154-161.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Graham F. L., van der Eb A. J., Heijneker H. L. Size and location of the transforming region in human adenovirus type 5 DNA. Nature. 1974 Oct 25;251(5477):687–691. doi: 10.1038/251687a0. [DOI] [PubMed] [Google Scholar]
  12. Houweling A., van den Elsen P. J., van der Eb A. J. Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA. Virology. 1980 Sep;105(2):537–550. doi: 10.1016/0042-6822(80)90054-9. [DOI] [PubMed] [Google Scholar]
  13. Mak I., Mak S. Transformation of rat cells by cyt mutants of adenovirus type 12 and mutants of adenovirus type 5. J Virol. 1983 Mar;45(3):1107–1117. doi: 10.1128/jvi.45.3.1107-1117.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Persson H., Katze M. G., Philipson L. Purification of a native membrane-associated adenovirus tumor antigen. J Virol. 1982 Jun;42(3):905–917. doi: 10.1128/jvi.42.3.905-917.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Prentki M., Biden T. J., Janjic D., Irvine R. F., Berridge M. J., Wollheim C. B. Rapid mobilization of Ca2+ from rat insulinoma microsomes by inositol-1,4,5-trisphosphate. Nature. 1984 Jun 7;309(5968):562–564. doi: 10.1038/309562a0. [DOI] [PubMed] [Google Scholar]
  16. Rowe D. T., Graham F. L. Transformation of rodent cells by DNA extracted from transformation-defective adenovirus mutants. J Virol. 1983 Jun;46(3):1039–1044. doi: 10.1128/jvi.46.3.1039-1044.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  18. Streb H., Irvine R. F., Berridge M. J., Schulz I. Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983 Nov 3;306(5938):67–69. doi: 10.1038/306067a0. [DOI] [PubMed] [Google Scholar]
  19. Subramanian T., Kuppuswamy M., Mak S., Chinnadurai G. Adenovirus cyt+ locus, which controls cell transformation and tumorigenicity, is an allele of lp+ locus, which codes for a 19-kilodalton tumor antigen. J Virol. 1984 Nov;52(2):336–343. doi: 10.1128/jvi.52.2.336-343.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Takemori N., Cladaras C., Bhat B., Conley A. J., Wold W. S. cyt gene of adenoviruses 2 and 5 is an oncogene for transforming function in early region E1B and encodes the E1B 19,000-molecular-weight polypeptide. J Virol. 1984 Dec;52(3):793–805. doi: 10.1128/jvi.52.3.793-805.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Takemori N., Riggs J. L., Aldrich C. Genetic studies with tumorigenic adenoviruses. I. Isolation of cytocidal (cyt) mutants of adenovirus type 12. Virology. 1968 Dec;36(4):575–586. doi: 10.1016/0042-6822(68)90189-x. [DOI] [PubMed] [Google Scholar]
  22. Van der Eb A. J., Mulder C., Graham F. L., Houweling A. Transformation with specific fragments of adenovirus DNAs. I. Isolation of specific fragments with transforming activity of adenovirus 2 and 5 DNA. Gene. 1977;2(3-4):115–132. doi: 10.1016/0378-1119(77)90012-9. [DOI] [PubMed] [Google Scholar]
  23. White E., Blose S. H., Stillman B. W. Nuclear envelope localization of an adenovirus tumor antigen maintains the integrity of cellular DNA. Mol Cell Biol. 1984 Dec;4(12):2865–2875. doi: 10.1128/mcb.4.12.2865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Závada J., Závadová Z., Russ G., Poláková K., Rajcáni J., Stencl J., Loksa J. Human cell surface proteins selectively assembled into vesicular stomatitis virus virions. Virology. 1983 Jun;127(2):345–360. doi: 10.1016/0042-6822(83)90149-6. [DOI] [PubMed] [Google Scholar]

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