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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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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