Tatebe H, Yanagida M
CREST Research Project, Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, Japan.
Curr Biol. 2000 Nov 2;10(21):1329-38. doi: 10.1016/s0960-9822(00)00773-9.
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 degrees C, but the molecular basis for Cut8 function is little understood.
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 Cut2 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.
Cut8 is a novel evolutionarily conserved heat-inducible regulator. It facilitates anaphase-promoting proteolysis by recruiting 26S proteasome to a functionally efficient nuclear location.
后期促进复合物（APC）/细胞周期体和26S蛋白酶体分别是有丝分裂周期蛋白多聚泛素化及降解和后期抑制因子Cut2（Pds1/分离酶）所必需的。在裂殖酵母中，细胞周期体和蛋白酶体有缺陷的突变细胞无法完成有丝分裂，具有超浓缩染色体和短纺锤体。在温度敏感型菌株cut8-563中，36℃时也会出现类似的表型，但对Cut8功能的分子基础了解甚少。
在高温下，Cut8的水平大幅增加，并且对于后期的进行变得至关重要。在cut8突变体中，会发生染色体错分离和异常的纺锤体动力学，但胞质分裂会在正常时间发生，导致出现cut表型。这是因为尽管在cut8突变体中Cdc13发生了多聚泛素化，但核中有丝分裂周期蛋白和Cut2的降解被显著延迟。Cut8主要定位于细胞核和核周，这种分布与26S蛋白酶体的分布高度相似。然而，在cut8突变体中，26S蛋白酶体大多位于细胞质中，这表明Cut8是其正确定位所必需的。
Cut8是一种新的进化保守的热诱导调节因子。它通过将26S蛋白酶体募集到功能高效的核位置来促进后期促进性蛋白水解。
