Nature Publishing Group, publisher of Nature, and other science journals and reference works
Nature
my account e-alerts subscribe register
   
Sunday 24 September 2017
Journal Home
Current Issue
AOP
Archive
Download PDF
References
Export citation
Export references
Send to a friend
More articles like this

Letters to Nature
Nature 384, 276 - 279 (21 November 1996); doi:10.1038/384276a0

20S cyclosome complex formation and proteolytic activity inhibited by the cAMP/PKA pathway

Yukiko M. Yamashita, Yukinobu Nakaseko, Itaru Samejima*, Kazuki Kumada, Hiroshi Yamada, David Michaelson & Mitsuhiro Yanagida

Department of Biophysics, Graduate School of Science, Kyoto University Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606, Japan
*Present address: Institute of Cell and Molecular Biology, King's Building, Mayfield Road, University of Edinburgh, Edinburgh EH9 3JR, UK.

THE 20S cyclosome complex (also known as the anaphase-promoting complex) has ubiquitin ligase activity and is required for mitotic cyclin destruction1–3 and sister chromatid separation4,5. The formation and activation of the 20S cyclosome complex is regulated by an unknown mechanism. Here we show that Cut4 (ref. 6) is an essential component of the cyclosome in fission yeast. Cut4 shares sequence similarity with BimE, a protein that regulates mitosis in Aspergittus nidulans 7–9. Mutations in cut4 result in hypersensitivity to cyclic AMP and to stress-inducing heavy metals, inhibition of the onset of anaphase, disruption of the 20S complex, and inhibition of mitotic cyclin ubiquitination. These phenotypes are fully suppressed by cAMP phosphodiesterase and the protein kinase A (PKA) regulatory subunit and weakly suppressed by Stil (an activator of the Hsp70 and Hsp90 chaperones10,11). Suppression correlates with the amount of 20S complex, indicating that cyclosome formation and activation is inhibited by the cAMP/PKA pathway.

  1. Sudakin, V. et al. Mol. Biol. Cell 6, 185−198 (1995). | PubMed | ISI | ChemPort |
  2. King, R. W. et al. Cell 81, 279−288 (1995). | Article | PubMed | ISI | ChemPort |
  3. Tugendreich, S., Tomkiel, J., Earnshaw, W. & Hieter, P. Cell 81, 261−268 (1995). | Article | PubMed | ISI | ChemPort |
  4. Irniger, S., Piatti, S., Michaelis, C. & Nasmyth, K. Cell 81, 269−277 (1995). | Article | PubMed | ISI | ChemPort |
  5. Funabiki, H. et al. Nature 381, 438−441 (1996). | Article | PubMed | ISI | ChemPort |
  6. Hirano, T., Funahashi, S., Uemura, T. & Yanagida, M. EMBO J. 5, 2973−2979 (1986). | ISI | ChemPort |
  7. Osmani, S. A., Engel, D. B., Doonan, J. H. & Morris, N. R. Cell 52, 241−251 (1988). | Article | PubMed | ISI | ChemPort |
  8. Engle, D. B. et al. J. Biol. Chem. 265, 16132−16137 (1990). | PubMed | ISI | ChemPort |
  9. James, S. W., Mirabito, P. M., Scacheri, P. C. & Morris, N. R. J. Cell. Sci. 108, 3495−3499 (1995).
  10. Chang, H.-C. J. & Lindquist, S. J. Biol. Chem. 269, 24983−24988 (1994). | PubMed | ISI | ChemPort |
  11. Schumacher, R. J. et al. J. Biol. Chem. 269, 9493−9499 (1994). | PubMed | ISI | ChemPort |
  12. Jungmann, J., Reins, H.-A., Schobert, C. & Jentsch, S. Nature 361, 369−371 (1993). | Article | PubMed | ISI | ChemPort |
  13. Seufert, W. & Jentsch, S. EMBO J. 9, 543−550 (1990). | PubMed | ISI | ChemPort |
  14. Devoti, J., Seydoux, G., Beach, D. & McLeod, M. EMBO J. 10, 3759−3786 (1991). | PubMed | ChemPort |
  15. Mochizuki, N. & Yamamoto, M. Mol. Gen. Genet. 233, 17−24 (1992). | Article | PubMed | ChemPort |
  16. Starborg, M., Brundell, E., Gell, K. & Höög, C. J. Biol. Chem. 269, 24133−24137 (1994). | PubMed | ISI | ChemPort |
  17. Hirano, T., Hiraoka, Y. & Yanagida, M. J. Cell Biol. 106, 1171−1183 (1988). | Article | PubMed | ISI | ChemPort |
  18. Samejima, I. & Yanagida, M. J. Cell Biol. 127, 1665−1670 (1994).
  19. Maundrell, K. J. Biol. Chem. 265, 10857−10864 (1990). | PubMed | ISI | ChemPort |
  20. Ishii, T., Kumada, K., Toda, T. & Yanagida, M. EMBO J. (in the press).
  21. Grieco, D., Porcellini, A., Awedimento, E. V. & Gottesman, M. Science 271, 1718−1722 (1996). | PubMed | ISI | ChemPort |
  22. Mizukami, T. et al. Cell 73, 121−132 (1993). | Article | PubMed | ISI | ChemPort |
  23. Rothstein, R. J. Meth. Enzymol. 101, 202−211 (1983). | Article | PubMed | ISI | ChemPort |
  24. MacNeil, S. A. & Fantes, P. in The Cell Cycle: A Practical Approach (eds Fantes, P. & Brooks, R.) 93−125 (Oxford Univ. Press, New York, 1993).
  25. Funabiki, H., Hagan, I., Uzawa, S. & Yanagida, M. J. Cell Biol. 121, 961−976 (1993). | Article | PubMed | ISI | ChemPort |
  26. Harlow, E. & Lane, D. Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1988).



© 1996 Nature Publishing Group
Privacy Policy