Schwab M, Lutum A S, Seufert W
Institute of Industrial Genetics, University of Stuttgart, Germany.
Cell. 1997 Aug 22;90(4):683-93. doi: 10.1016/s0092-8674(00)80529-2.
Stage-specific proteolysis of mitotic cyclins is fundamental to eukaryotic cell cycle regulation. We found that yeast Hct1, a conserved protein of eukaryotes, is a necessary and rate-limiting component of this proteolysis pathway. In hct1 mutants, the mitotic cyclin Clb2 is highly stabilized and inappropriately induces DNA replication, while G1 cyclins and other proteolytic substrates remain short-lived. Viability of hct1 mutants depends on SIC1. This and further results suggest that inhibition of cyclin-dependent kinases may compensate for defects in cyclin proteolysis. Remarkably, elevated levels of Hct1 ectopically activate destruction box- and Cdc23-dependent degradation of Clb2 and cause phenotypic effects characteristic for a depletion of M-phase cyclins. Hct1 and the related Cdc20 may function as substrate-specific regulators of proteolysis during mitosis.
有丝分裂周期蛋白的阶段特异性蛋白水解对于真核细胞周期调控至关重要。我们发现酵母Hct1，一种真核生物的保守蛋白，是该蛋白水解途径的必要且限速成分。在hct1突变体中，有丝分裂周期蛋白Clb2高度稳定并不适当地诱导DNA复制，而G1周期蛋白和其他蛋白水解底物寿命仍然较短。hct1突变体的生存能力取决于SIC1。这一结果及其他结果表明，细胞周期蛋白依赖性激酶的抑制可能补偿细胞周期蛋白蛋白水解的缺陷。值得注意的是，Hct1水平升高会异位激活Clb2的破坏框和Cdc23依赖性降解，并导致M期周期蛋白耗竭的特征性表型效应。Hct1和相关的Cdc20可能在有丝分裂期间作为蛋白水解的底物特异性调节因子发挥作用。
