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. 1974 Feb 1;60(2):337–345. doi: 10.1083/jcb.60.2.337

REGULATION OF TYROSINE AMINOTRANSFERASE ACTIVITY IN TWO LIVER-DERIVED PERMANENT CELL LINES

Larry Sellers 1, Daryl Granner 1
PMCID: PMC2109159  PMID: 4149773

Abstract

The regulation of tyrosine aminotransferase (TAT) activity has been examined in two liver-derived heteroploid cell lines. One (hepatoma tissue culture cells [HTC]) was derived from a hepatoma, the other (rat liver culture cells [RLC]) was derived from normal liver. The two cell lines show the following striking similarities in the control of this specific protein: (a) The kinetics of TAT induction by dexamethasone phosphate (DxP) are similar in randomly growing cells of both lines; (b) During mitosis and early G1 phase of the cell cycle TAT activity cannot be induced by DxP in either cell line; (c) 2–3 h into G1, when both lines become sensitive to inducer, basal enzyme activity declines to a new steady-state level; (d) Preinduced cells collected in mitosis show approximately twice the level of TAT activity as fully induced, randomly growing cultures and this activity is maintained in early G1 with or without the inducer; and (e) Inhibition of RNA synthesis by 5 µg/ml of actinomycin D in preinduced, synchronized cells allows TAT activity to remain at constitutive levels throughout G1, even in the absence of inducer. These results are presented in support of a previously described model which states that glucocorticoid hormones exert posttranscriptional control of the synthesis of specific proteins in mammalian cells.

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Selected References

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  1. BARNABEI O., SERENI F. [Induction of tyrosine-alpha-ketoglutarate transaminase activity in the isolated rat liver]. Boll Soc Ital Biol Sper. 1960 Dec 31;36:1656–1658. [PubMed] [Google Scholar]
  2. Balhorn R., Bordwell J., Sellers L., Granner D., Chalkley R. Histone phosphorylation and DNA synthesis are linked in synchronous cultures of HTC cells. Biochem Biophys Res Commun. 1972 Feb 16;46(3):1326–1333. doi: 10.1016/s0006-291x(72)80120-7. [DOI] [PubMed] [Google Scholar]
  3. Bello L. J. Studies on gene activity in synchronized culture of mammalian cells. Biochim Biophys Acta. 1969 Mar 18;179(1):204–213. doi: 10.1016/0005-2787(69)90137-3. [DOI] [PubMed] [Google Scholar]
  4. Brent T. P., Butler J. A., Crathorn A. R. Variations in phosphokinase activities during the cell cycle in synchronous populations of HeLa cells. Nature. 1965 Jul 10;207(993):176–177. doi: 10.1038/207176a0. [DOI] [PubMed] [Google Scholar]
  5. DeLuca C., Massaro E. J., Cohen M. M. Biochemical and cytogenetic characterization of rat hepatoma cell lines in vitro. Cancer Res. 1972 Nov;32(11):2435–2440. [PubMed] [Google Scholar]
  6. Friedman S. J., Bellantone R. A., Canellakis E. S. Ornithine decarboxylase activity in synchronously growing Don C cells. Biochim Biophys Acta. 1972 Jan 28;261(1):188–193. doi: 10.1016/0304-4165(72)90329-7. [DOI] [PubMed] [Google Scholar]
  7. GOLDSTEIN L., STELLA E. J., KNOX W. E. The effect of hydrocortisone on tyrosine-alpha-ketoglutarate transaminase and tryptophan pyrrolase activities in the isolated, perfused rat liver. J Biol Chem. 1962 May;237:1723–1726. [PubMed] [Google Scholar]
  8. Gelbard A. S., Kim J. H., Perez A. G. Fluctuations in deoxycytidine monophosphate deaminase activity during the cell cycle in synchronous populations of HeLa cells. Biochim Biophys Acta. 1969 Jun 17;182(2):564–566. doi: 10.1016/0005-2787(69)90209-3. [DOI] [PubMed] [Google Scholar]
  9. Gerschenson L. E., Andersson M., Molson J., Okigaki T. Tyrosine transaminase induction by dexamethasone in a new rat liver cell line. Science. 1970 Nov 20;170(3960):859–861. doi: 10.1126/science.170.3960.859. [DOI] [PubMed] [Google Scholar]
  10. Granner D. K., Hayashi S., Thompson E. B., Tomkins G. M. Stimulation of tyrosine aminotransferase synthesis by dexamethasone phosphate in cell culture. J Mol Biol. 1968 Jul 28;35(2):291–301. doi: 10.1016/s0022-2836(68)80025-7. [DOI] [PubMed] [Google Scholar]
  11. Granner D. K., Thompson E. B., Tomkins G. M. Dexamethasone phosphate-induced synthesis of tyrosine aminotransferase in hepatoma tissue culture cells. Studies of the early phases of induction and of the steroid requirement for maintanance of the induced rate of synthesis. J Biol Chem. 1970 Mar 25;245(6):1472–1478. [PubMed] [Google Scholar]
  12. Hager C. B., Kenney F. T. Regulation of tyrosine-alpha-ketoglutarate transaminase in rat liver. VII. Hormonal effects of synthesis in the isolated, perfused liver. J Biol Chem. 1968 Jun 25;243(12):3296–3300. [PubMed] [Google Scholar]
  13. Hayashi S. I., Granner D. K., Tomkins G. M. Tyrosine aminotransferase. Purificaton and characterization. J Biol Chem. 1967 Sep 25;242(18):3998–4006. [PubMed] [Google Scholar]
  14. JACOB F., MONOD J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961 Jun;3:318–356. doi: 10.1016/s0022-2836(61)80072-7. [DOI] [PubMed] [Google Scholar]
  15. KENNEY F. T. Induction of tyrosine-alpha-ketoglutarate transaminase in rat liver. IV. Evidence for an increase in the rate of enzyme synthesis. J Biol Chem. 1962 Nov;237:3495–3498. [PubMed] [Google Scholar]
  16. Klevecz R. R., Ruddle F. H. Cyclic changes in enzyme activity in synchronized mammalian cell cultures. Science. 1968 Feb 9;159(3815):634–636. doi: 10.1126/science.159.3815.634. [DOI] [PubMed] [Google Scholar]
  17. Klevecz R. R. Temporal order in mammalian cells. I. The periodic synthesis of lactate dehydrogenase in the cell cycle. J Cell Biol. 1969 Nov;43(2):207–219. doi: 10.1083/jcb.43.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LIN E. C., KNOX W. E. Specificity of the adaptive response to tyrosine-alpha-ketoglutarate transaminase in the rat. J Biol Chem. 1958 Nov;233(5):1186–1189. [PubMed] [Google Scholar]
  19. Levisohn S. R., Thompson E. B. Tyrosine aminotransferase induction regulation variant in tissue culture. Nat New Biol. 1972 Jan 26;235(56):102–104. doi: 10.1038/newbio235102a0. [DOI] [PubMed] [Google Scholar]
  20. Littlefield J. W. The periodic synthesis of thymidine kinase in mouse fibroblasts. Biochim Biophys Acta. 1966 Feb 21;114(2):398–403. doi: 10.1016/0005-2787(66)90319-4. [DOI] [PubMed] [Google Scholar]
  21. Martin D. W., Jr, Tomkins G. M., Bresler M. A. Control of specific gene expression examined in synchronized mammalian cells. Proc Natl Acad Sci U S A. 1969 Jul;63(3):842–849. doi: 10.1073/pnas.63.3.842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Martin D. W., Jr, Tomkins G. M. The appearance and disappearance of the post-transcriptional repressor of tyrosine aminotransferase synthesis during the HTC cell cycle. Proc Natl Acad Sci U S A. 1970 Apr;65(4):1064–1068. doi: 10.1073/pnas.65.4.1064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Martin D., Jr, Tomkins G. M., Granner D. Synthesis and induction of tyrosine aminotransferase in synchronized hepatoma cells in culture. Proc Natl Acad Sci U S A. 1969 Jan;62(1):248–255. doi: 10.1073/pnas.62.1.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. PITOT H. C., PERAINO C., MORSE P. A., Jr, POTTER V. R. HEPATOMAS IN TISSUE CULTURE COMPARED WITH ADAPTING LIVER IN VIVO. Natl Cancer Inst Monogr. 1964 Apr;13:229–245. [PubMed] [Google Scholar]
  25. Palmiter R. D., Schimke R. T. Regulation of protein synthesis in chick oviduct. 3. Mechanism of ovalbumin "superinduction" by actinomycin D. J Biol Chem. 1973 Mar 10;248(5):1502–1512. [PubMed] [Google Scholar]
  26. Peterkofsky B., Tomkins G. M. Effect of inhibitors of nucleic acid synthesis on steroid-mediated induction of tyrosine aminotransferase in hepatoma cell cultures. J Mol Biol. 1967 Nov 28;30(1):49–61. doi: 10.1016/0022-2836(67)90242-2. [DOI] [PubMed] [Google Scholar]
  27. Potter V. R., Watanabe M., Pitot H. C., Morris H. P. Systematic oscillations in metabolic activity in rat liver and hepatomas. Survey of normal diploid and other hepatoma lines. Cancer Res. 1969 Jan;29(1):55–78. [PubMed] [Google Scholar]
  28. Richardson U. I., Tashjian A. H., Jr, Levine L. Establishment of a clonal strain of hepatoma cells which secrete albumin. J Cell Biol. 1969 Jan;40(1):236–247. doi: 10.1083/jcb.40.1.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thompson E. B., Granner D. K., Tomkins G. M. Superinduction of tyrosine aminotransferase by actinomycin D in rat hepatoma (HTC) cells. J Mol Biol. 1970 Dec 14;54(2):159–175. doi: 10.1016/0022-2836(70)90424-9. [DOI] [PubMed] [Google Scholar]
  30. Thompson E. B., Tomkins G. M., Curran J. F. Induction of tyrosine alpha-ketoglutarate transaminase by steroid hormones in a newly established tissue culture cell line. Proc Natl Acad Sci U S A. 1966 Jul;56(1):296–303. doi: 10.1073/pnas.56.1.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tomkins G. M., Gelehrter T. D., Granner D., Martin D., Jr, Samuels H. H., Thompson E. B. Control of specific gene expression in higher organisms. Expression of mammalian genes may be controlled by repressors acting on the translation of messenger RNA. Science. 1969 Dec 19;166(3912):1474–1480. doi: 10.1126/science.166.3912.1474. [DOI] [PubMed] [Google Scholar]
  32. Tomkins G. M., Levinson B. B., Baxter J. D., Dethlefsen L. Further evidence for posttranscriptional control of inducible tyrosine aminotransferase synthesis in cultured hepatoma cells. Nat New Biol. 1972 Sep 6;239(88):9–14. doi: 10.1038/newbio239009a0. [DOI] [PubMed] [Google Scholar]
  33. Volpe P. Depression of ornithine-delta-transaminase synchronized with the life cycle of Hela cells cultivated in suspension. Biochem Biophys Res Commun. 1969 Jan 27;34(2):190–195. doi: 10.1016/0006-291x(69)90630-5. [DOI] [PubMed] [Google Scholar]

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