1887

Abstract

Proteolysis triggered by the anaphase-promoting complex/cyclosome (APC/C) is essential for the progression through mitosis. APC/C is a highly conserved ubiquitin ligase whose activity is regulated during the cell cycle by various factors, including spindle checkpoint components and protein kinases. The cAMP-dependent protein kinase (PKA) was identified as negative regulator of APC/C in yeast and mammalian cells. In the yeast , PKA activity is induced upon glucose addition or by activated Ras proteins. This study shows that glucose and the activated Ras2 protein synergistically inhibit APC/C function via the cAMP/PKA pathway in yeast. Remarkably, Ras2 proteins defective in the interaction with adenylate cyclase fail to influence APC/C, implying that its function is regulated exclusively by PKA, but not by alternative Ras pathways. Furthermore, it is shown that the three PKAs in yeast, Tpk1, Tpk2 and Tpk3, have redundant functions in regulating APC/C in response to glucose medium. Single or double deletions of genes did not prevent inhibition of APC/C, suggesting that each of the Tpk proteins can take over this function. However, Tpk2 seems to inhibit APC/C function more efficiently than Tpk1 and Tpk3. Finally, evidence is provided that Cdc20 is involved in APC/C regulation by the cAMP/PKA pathway.

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2003-05-01
2024-04-19
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References

  1. Alberghina L., Smeraldi C., Ranzi B. M., Porro D. 1998; Control by nutrients of growth and cell cycle progression in budding yeast, analyzed by double-tag flow cytometry. J Bacteriol 180:3864–3872
    [Google Scholar]
  2. Amon A. 2001; Together until separin do us part. Nat Cell Biol 3:E12–E14
    [Google Scholar]
  3. Anghileri P., Branduardi P., Sternieri F., Monti P., Visintin R., Bevilacqua A., Alberghina L., Martegani E., Baroni M. D. 1999; Chromosome separation and exit from mitosis in budding yeast: dependence on growth revealed by cAMP-mediated inhibition. Exp Cell Res 250:510–523
    [Google Scholar]
  4. Broach J. R. 1991; RAS genes in Saccharomyces cerevisiae : signal transduction in search of a pathway. Trends Genet 7:28–33
    [Google Scholar]
  5. Broek D., Toda T., Michaeli T., Levin L., Birchmeier C., Zoller M., Powers S., Wigler M. 1987; The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Cell 48:789–799
    [Google Scholar]
  6. Colombo S., Ma P., Cauwenberg L. 8 other authors 1998; Involvement of distinct G-proteins, Gpa2 and Ras, in glucose- and intracellular acidification-induced cAMP signalling in the yeast Saccharomyces cerevisiae . EMBO J 17:3326–3341
    [Google Scholar]
  7. Gardner R. D., Burke D. J. 2000; The spindle checkpoint: two transitions, two pathways. Trends Cell Biol 10:154–158
    [Google Scholar]
  8. Golan A., Yudkovsky Y., Hershko A. 2002; The cyclin-ubiquitin ligase activity of cyclosome/APC is jointly activated by protein kinases Cdk1-cyclin B and Plk. J Biol Chem 277:15552–15557
    [Google Scholar]
  9. Güldener U., Heck S., Fielder T., Beinhauer J., Hegemann J. H. 1996; A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res 24:2519–2524
    [Google Scholar]
  10. Harper J. W., Burton J. L., Solomon M. J. 2002; The anaphase-promoting complex: it's not just for mitosis any more. Genes Dev 16:2179–2206
    [Google Scholar]
  11. Hilioti Z., Chung Y. S., Mochizuki Y., Hardy C. F., Cohen-Fix O. 2001; The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner. Curr Biol 11:1347–1352
    [Google Scholar]
  12. Irniger S., Bäumer M., Braus G. H. 2000; Glucose and Ras activity influence the ubiquitin ligases APC/C and SCF in Saccharomyces cerevisiae . Genetics 154:1509–1521
    [Google Scholar]
  13. Kennelly P. J., Krebs E. G. 1991; Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem 266:15555–15558
    [Google Scholar]
  14. Kotani S., Tugendreich S., Fujii M., Jorgensen P. M., Watanabe N., Hoog C., Hieter P., Todokoro K. 1998; PKA and MPF-activated polo-like kinase regulate anaphase-promoting complex activity and mitosis progression. Mol Cell 1:371–380
    [Google Scholar]
  15. Kotani S., Tanaka H., Yasuda H., Todokoro K. 1999; Regulation of APC activity by phosphorylation and regulatory factors. J Cell Biol 146:791–800
    [Google Scholar]
  16. Kron S. J., Styles C. A., Fink G. R. 1994; Symmetric cell division in pseudohyphae of the yeast Saccharomyces cerevisiae . Mol Biol Cell 5:1003–1022
    [Google Scholar]
  17. Mazon M. J., Behrens M. M., Morgado E., Portillo F. 1993; Low activity of the yeast cAMP-dependent protein kinase catalytic subunit Tpk3 is due to the poor expression of the TPK3 gene. Eur J Biochem 213:501–506
    [Google Scholar]
  18. Morgan D. O. 1999; Regulation of the APC and the exit from mitosis. Nat Cell Biol 1:E47–E53
    [Google Scholar]
  19. Mösch H. U. 2000; Pseudohyphal development of Saccharomyces cerevisiae . Contrib Microbiol 5:185–200
    [Google Scholar]
  20. Mösch H. U., Kubler E., Krappmann S., Fink G. R., Braus G. H. 1999; Crosstalk between the Ras2p-controlled mitogen-activated protein kinase and cAMP pathways during invasive growth of Saccharomyces cerevisiae . Mol Biol Cell 10:1325–1335
    [Google Scholar]
  21. Nasmyth K. 2002; Segregating sister genomes: the molecular biology of chromosome separation. Science 297:559–565
    [Google Scholar]
  22. Nigg E. A. 2001; Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2:21–32
    [Google Scholar]
  23. Peters J. M. 2002; The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9:931–943
    [Google Scholar]
  24. Pfleger C. M., Lee E., Kirschner M. W. 2001; Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex. Genes Dev 15:2396–2407
    [Google Scholar]
  25. Robertson L. S., Fink G. R. 1998; The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc Natl Acad Sci U S A 95:13783–13787
    [Google Scholar]
  26. Robertson L. S., Causton H. C., Young R. A., Fink G. R. 2000; The yeast A kinases differentially regulate iron uptake and respiratory function. Proc Natl Acad Sci U S A 97:5984–5988
    [Google Scholar]
  27. Robinson L. C., Gibbs J. B., Marshall M. S., Sigal I. S., Tatchell K. 1987; CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae . Science 235:1218–1221
    [Google Scholar]
  28. Rose M. D., Winston F., Hieter P. 1990 Laboratory Course Manual for Methods in Yeast Genetics Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  29. Rua D., Tobe B. T., Kron S. J. 2001; Cell cycle control of yeast filamentous growth. Curr Opin Microbiol 4:720–727
    [Google Scholar]
  30. Rudner A. D., Murray A. W. 2000; Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex. J Cell Biol 149:1377–1390
    [Google Scholar]
  31. Schwab M., Neutzner M., Mocker D., Seufert W. 2001; Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. EMBO J 20:5165–5175
    [Google Scholar]
  32. Shirayama M., Zachariae W., Ciosk R., Nasmyth K. 1998; The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae . EMBO J 17:1336–1349
    [Google Scholar]
  33. Stevenson B. J., Rhodes N., Errede B., Sprague G. F. Jr 1992; Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. Genes Dev 6:1293–1304
    [Google Scholar]
  34. Surana U., Amon A., Dowzer C., McGrew J., Byers B., Nasmyth K. 1993; Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. EMBO J 12:1969–1978
    [Google Scholar]
  35. Thevelein J. M., de Winde J. H. 1999; Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae . Mol Microbiol 33:904–918
    [Google Scholar]
  36. Toda T., Cameron S., Sass P., Zoller M., Wigler M. 1987; Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell 50:277–287
    [Google Scholar]
  37. Toda T., Uno I., Ishikawa T., Powers S., Kataoka T., Broek D., Cameron S., Broach J., Matsumoto K., Wigler M. 1985; In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell 40:27–36
    [Google Scholar]
  38. Vodermaier H. C. 2001; Cell cycle: waiters serving the destruction machinery. Curr Biol 11:R834–R837
    [Google Scholar]
  39. Yamada H., Kumada K., Yanagida M. 1997; Distinct subunit functions and cell cycle regulated phosphorylation of 20S APC/cyclosome required for anaphase in fission yeast. J Cell Sci 110:1793–1804
    [Google Scholar]
  40. Yamashita Y. M., Nakaseko Y., Samejima I., Kumada K., Yamada H., Michaelson D., Yanagida M. 1996; 20S cyclosome complex formation and proteolytic activity inhibited by the cAMP/PKA pathway. Nature 384:276–279
    [Google Scholar]
  41. Zachariae W., Nasmyth K. 1999; Whose end is destruction: cell division and the anaphase-promoting complex. Genes Dev 13:2039–2058
    [Google Scholar]
  42. Zachariae W., Schwab M., Nasmyth K., Seufert W. 1998; Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. Science 282:1721–1724
    [Google Scholar]
  43. Zähringer H., Holzer H., Nwaka S. 1998; Stability of neutral trehalase during heat stress in Saccharomyces cerevisiae is dependent on the activity of the catalytic subunits of cAMP-dependent protein kinase, Tpk1 and Tpk2. Eur J Biochem 255:544–551
    [Google Scholar]
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