Cooper K F, Mallory M J, Smith J B, Strich R
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
EMBO J. 1997 Aug 1;16(15):4665-75. doi: 10.1093/emboj/16.15.4665.
The ume3-1 allele was identified as a mutation that allowed the aberrant expression of several meiotic genes (e.g. SPO11, SPO13) during mitotic cell division in Saccharomyces cerevisiae. Here we report that UME3 is also required for the full repression of the HSP70 family member SSA1. UME3 encodes a non-essential C-type cyclin (Ume3p) whose levels do not vary through the mitotic cell cycle. However, Ume3p is destroyed during meiosis or when cultures are subjected to heat shock. Ume3p mutants resistant to degradation resulted in a 2-fold reduction in SPO13 mRNA levels during meiosis, indicating that the down-regulation of this cyclin is important for normal meiotic gene expression. Mutational analysis identified two regions (PEST-rich and RXXL) that mediate Ume3p degradation. A third destruction signal lies within the highly conserved cyclin box, a region that mediates cyclin-cyclin-dependent kinase (Cdk) interactions. However, the Cdk activated by Ume3p (Ume5p) is not required for the rapid destruction of this cyclin. Finally, Ume3p destruction was not affected in mutants defective for ubiquitin-dependent proteolysis. These results support a model in which Ume3p, when exposed to heat shock or sporulation conditions, is targeted for destruction to allow the expression of genes necessary for the cell to respond correctly to these environmental cues.
ume3-1等位基因被鉴定为一种突变，该突变使得酿酒酵母在有丝分裂细胞分裂过程中几个减数分裂基因（如SPO11、SPO13）出现异常表达。在此我们报告，UME3对于HSP70家族成员SSA1的完全抑制也是必需的。UME3编码一种非必需的C型细胞周期蛋白（Ume3p），其水平在有丝分裂细胞周期中无变化。然而，Ume3p在减数分裂期间或培养物受热激时会被降解。对降解具有抗性的Ume3p突变体导致减数分裂期间SPO13 mRNA水平降低2倍，表明这种细胞周期蛋白的下调对于正常减数分裂基因表达很重要。突变分析确定了介导Ume3p降解的两个区域（富含PEST和RXXL）。第三个破坏信号位于高度保守的细胞周期蛋白框内，该区域介导细胞周期蛋白 - 细胞周期蛋白依赖性激酶（Cdk）相互作用。然而，由Ume3p激活的Cdk（Ume5p）对于这种细胞周期蛋白的快速降解并非必需。最后，在泛素依赖性蛋白水解缺陷的突变体中，Ume3p的降解不受影响。这些结果支持了一个模型，即当Ume3p暴露于热激或孢子形成条件时，它会被靶向降解，以允许细胞正确响应这些环境信号所需的基因表达。
