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Cyclin-dependent kinase and Cks/Suc1 interact with the proteasome in yeast to control proteolysis of M-phase targets.

The Scripps Research Institute, MB7, La Jolla, California 92037, USA.
Genes & Development (Impact Factor: 12.64). 06/1999; 13(9):1190-202. DOI: 10.1101/gad.13.9.1190
Source: PubMed

ABSTRACT Cell cycle-specific proteolysis is critical for proper execution of mitosis in all eukaryotes. Ubiquitination and subsequent proteolysis of the mitotic regulators Clb2 and Pds1 depend on the cyclosome/APC and the 26S proteasome. We report here that components of the cell cycle machinery in yeast, specifically the cell cycle regulatory cyclin-dependent kinase Cdc28 and a conserved associated protein Cks1/Suc1, interact genetically, physically, and functionally with components of the 26S proteasome. A mutation in Cdc28 (cdc28-1N) that interferes with Cks1 binding, or inactivation of Cks1 itself, confers stabilization of Clb2, the principal mitotic B-type cyclin in budding yeast. Surprisingly, Clb2-ubiquitination in vivo and in vitro is not affected by mutations in cks1, indicating that Cks1 is not essential for cyclosome/APC activity. However, mutant Cks1 proteins no longer physically interact with the proteasome, suggesting that Cks1 is required for some aspect of proteasome function during M-phase-specific proteolysis. We further provide evidence that Cks1 function is required for degradation of the anaphase inhibitor Pds1. Stabilization of Pds1 is partially responsible for the metaphase arrest phenotype of cks1 mutants because deletion of PDS1 partially relieves the metaphase block in these mutants.

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    • "In a similar way, the CDK1–CycB–CKS complex phosphorylates the sub-unit CDC27 of the anaphase promoting complex, which is crucial for the ubiquitination of cyclin B and further exit from mitosis [10]. Once cyclin B has been ubiquitinated, interaction between the CKS and the proteasome is necessary for actual proteolysis of the cyclin [11] [12]. The human protein hCKS1 associates with SKP2, a subunit of the SCF-ubiquitin-ligase complex, and favors the ubiquitination of the CKI (cdk inhibitor) p27 Kip1 and thus the G1/S transition [13] [14]. "
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    • "As a result, the mitosispromoting factor (MPF) becomes inactive because of the destruction of cyclin B, and the cell exits from the cycle before mitosis. Cks1 also plays a role here by helping unbiquitinated cyclin B to move toward the proteasome, where it is degraded, as demonstrated in budding yeast (Kaiser et al., 1999). Cks1 in Caenorhabditis elegans, one of the two Cks proteins in this organism, is also required for mitotic exit and for the completion of maternal meiotic divisions (Polinko and Strome, 2000). "
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    ABSTRACT: A full-length Cks1 homologue gene, AmphiCks1, was identified in amphioxus, Branchiostoma belcheri tsingtauense. Sequence characteristics, phylogeny and patterns of expression during embryonic and larval development were established. The protein predicted from AmphiCks1 showed high sequence identity with vertebrate and invertebrate homologues. Protein structural studies and phylogenetic analysis suggested that Cks homologues are evolutionarily conserved. The AmphiCks1 transcript was detected in most early developmental stages by northern blotting and whole-mount in situ hybridization, suggesting a role for the gene in cell division.
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    • "Cic1 was not identi®ed in the puri®cation of the 19S core complex from budding yeast (Glickman et al., 1998) and in 26S puri®cation experiments (Verma et al., 2000). Like Cic1, a number of additional proteins so far have been reported to be associated with the 26S proteasome (Fujimuro et al., 1998; Schauber et al., 1998; Kaiser et al., 1999; Papa et al., 1999; Russell et al., 1999a; Verma et al., 2000; Xie and Varshavsky, 2000). This either implies a ¯exible association of these additional factors with the 26S proteasome, or they represent speci®c subunits of 26S proteasomal subpopulations. "
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