Cut8, essential for anaphase, controls localization of 26S proteasome, facilitating destruction of cyclin and Cut2

Background: Anaphase-promoting complex (APC)/cyclosome and 26S proteasome are respectively required for polyubiquitination and degradation of mitotic cyclin and anaphase inhibitor Cut2 (Pds1/securin). In fission yeast, mutant cells defective in cyclosome and proteasome fail to complete mitosis and have hypercondensed chromosomes and a short spindle. A similar phenotype is seen in a temperature-sensitive strain cut8-563 at 36 degreesC, but the molecular basis for Cut8 function is little understood. Results: At high temperature, the level of Cut8 greatly increases and it becomes essential to the progression of anaphase. In cut8 mutants, chromosome mis-segregation and aberrant spindle dynamics occur, but cytokinesis takes place with normal timing, leading to the cut phenotype. This is due to the fact that destruction of mitotic cyclin and Cut? in the nucleus is dramatically delayed, though polyubiquitination of Cdc13 occurs in cut8 mutant. Cut8 is localized chiefly to the nucleus and nuclear periphery, a distribution highly similar to that of 26S proteasome. In cut8 mutant, however, 26S proteasome becomes mostly cytoplasmic, showing that Cut8 is needed for its proper localization. Conclusion: Cut8 is a novel evolutionarily conserved heat-inducible regulator. It facilitates anaphase-promoting proteolysis by recruiting 26S proteasome to a functionally efficient nuclear location.