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Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast

Abstract

Cks proteins are small evolutionarily conserved proteins that interact genetically and physically with cyclin-dependent kinases. However, in spite of a large body of genetic, biochemical and structural research, no compelling unifying model of their functions has emerged1,2. Here we show, by investigating the essential role of Cks1 in Saccharomyces cerevisiae, that the protein is primarily involved in promoting mitosis by modulating the transcriptional activation of the APC/C protein–ubiquitin ligase activator Cdc20. Cks1 is required for both the periodic dissociation of Cdc28 kinase from the CDC20 promoter and the periodic association of the proteasome with the promoter. We propose that the essential role of Cks1 is to recruit the proteasome to, and/or dissociate the Cdc28 kinase from, the CDC20 promoter, thus facilitating transcription by remodelling transcriptional complexes or chromatin associated with the CDC20 gene.

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Figure 1: Cks1 is involved in the transcriptional regulation of CDC20.
Figure 2: Cks1 associates with the upstream activating sequence (UAS)/promoter of CDC20.
Figure 3: Components of the 19S and 20S proteasome particles interact with the promoter of CDC20.
Figure 4: Proteasomal function is essential for CDC20 transcription.

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References

  1. Endicott, J. A. & Nurse, P. The cell cycle and suc1: From structure to function? Structure 3, 321–325 (1995)

    Article  CAS  Google Scholar 

  2. Pines, J. Cell cycle: Reaching for a role for the Cks proteins. Curr. Biol. 6, 1399–1402 (1996)

    Article  CAS  Google Scholar 

  3. Tang, Y. & Reed, S. I. The cdk-associated protein Cks1 functions both in G1 and G2 in Saccharomyces cerevisiae. Genes Dev. 7, 822–832 (1993)

    Article  CAS  Google Scholar 

  4. Kaiser, P. et al. Cyclin-dependent kinase and Cks/Suc1 interact with the proteasome in yeast to control proteolysis of M-phase targets. Genes Dev. 13, 1190–1202 (1999)

    Article  CAS  Google Scholar 

  5. Ghiara, J. B. et al. A cyclin B homolog in S. cerevisiae: Chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis. Cell 65, 163–174 (1991)

    Article  CAS  Google Scholar 

  6. Amon, A., Tyers, M., Futcher, B. & Nasmyth, K. Mechanisms that help the yeast cell cycle clock tick: G2 cyclins transcriptionally activate G2 cyclins and repress G1 cyclins. Cell 74, 993–1007 (1993)

    Article  CAS  Google Scholar 

  7. Nasmyth, K. Control of the yeast cell cycle by the cdc28 protein kinase. Curr. Opin. Cell Biol. 5, 166–179 (1993)

    Article  CAS  Google Scholar 

  8. Visintin, R., Prinz, S. & Amon, A. Cdc20 and cdh1: A family of substrate-specific activators of APC-dependent proteolysis. Science 278, 460–463 (1997)

    Article  ADS  CAS  Google Scholar 

  9. Lim, H. H., Goh, P.-Y. & Surana, U. Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and clb2 during M phase in budding yeast. Curr. Biol. 8, 231–234 (1998)

    Article  CAS  Google Scholar 

  10. Jensen, S., Segal, M., Clarke, D. J. & Reed, S. I. A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1. J. Cell Biol. 152, 27–40 (2001)

    Article  CAS  Google Scholar 

  11. Spellman, P. T. et al. Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol. Biol. Cell 9, 3273–3297 (1998)

    Article  CAS  Google Scholar 

  12. Maher, M., Cong, F., Kindelberger, D., Nasmyth, K. & Dalton, S. Cell cycle-regulated transcription of the CLB2 gene is dependent on Mcm1 and a ternary complex factor. Mol. Cell. Biol. 15, 3129–3137 (1995)

    Article  CAS  Google Scholar 

  13. Pic, A. et al. The forkhead protein Fkh2 is a component of the yeast cell cycle transcription factor SFF. EMBO J. 19 14, 3750–3761 (2000)

    Article  CAS  Google Scholar 

  14. Koranda, M., Schleiffer, A., Endler, L. & Ammerer, G. Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters. Nature 406, 94–98 (2000)

    Article  ADS  CAS  Google Scholar 

  15. Zhu, G. et al. Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth. Nature 406, 90–94 (2000)

    Article  ADS  CAS  Google Scholar 

  16. Bourne, Y. et al. Crystal structure and mutational analysis of the human cdk2 kinase complex with cell cycle-regulatory protein CksHs1. Cell 84, 863–874 (1996)

    Article  CAS  Google Scholar 

  17. Ferdous, A., Gonzalez, F., Sun, L., Kodadek, T. & Johnston, S. A. The 19S regulatory particle of the proteasome is required for efficient transcription elongation by RNA polymerase. Mol. Cell 7, 981–991 (2001)

    Article  CAS  Google Scholar 

  18. Gonzalez, F., Delahodde, A., Kodadek, T. & Johnston, S. A. Recruitment of a 19S proteasome subcomplex to an activated promoter. Science 296, 548–550 (2002)

    Article  ADS  CAS  Google Scholar 

  19. Hilt, W., Enenkel, C., Gruhler, A., Singer, T. & Wolf, D. H. The PRE4 gene codes for a subunit of the yeast proteasome necessary for peptidylglutamyl-peptide-hydrolyzing activity. Mutations link proteasome and stress- and ubiquitin-dependent proteolysis. J. Biol. Chem. 268, 3479–3486 (1993)

    CAS  PubMed  Google Scholar 

  20. Guthrie, C., Fink, G. R. Guide to Yeast Genetics and Molecular Biology 194 (Academic, San Diego, California, 1991)

  21. Reed, S. I., Hadwiger, J. A. & Lorincz, A. Protein kinase activity associated with the product of the yeast cell division cycle gene CDC28. Proc. Natl Acad. Sci. USA 82, 4055–4059 (1985)

    Article  ADS  CAS  Google Scholar 

  22. Collart, M. A. & Oliviero, S. in Current Protocols in Molecular Biology Vol. 2, 13.12 (Current Protocols, Wiley and Sons, New York, 1993)

    Google Scholar 

  23. Kaiser, P., Flick, K., Wittenberg, C. & Reed, S. I. Regulation of transcription by ubiquitination without proteolysis: Cdc34/SCFMet30-mediated inactivation of the transcription factor Met4. Cell 102, 303–314 (2000)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank S. A. Johnston for the sug1-25 strain, M. Koranda and G. Ammerer for the tagged Mcm1 and Ndd1 strains, K. Nasymth for the myc18-CDC20 allele, D. Wolff for the pre1 and pre4 strains used to construct the double mutant in our strain background, and K. Flick and S. Haase for discussions and technical advice about northern blotting experiments and ChIP assays. This work was supported by a grant from the NIH to S.I.R. M.C.M. acknowledges fellowship support from the International Agency for Research on Cancer and the Swiss National Science Foundation, and P.K. acknowledges fellowship support from the Austrian Science Foundation.

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Correspondence to Steven I. Reed.

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Morris, M., Kaiser, P., Rudyak, S. et al. Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast. Nature 423, 1009–1013 (2003). https://doi.org/10.1038/nature01720

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