Pries Ralph, Bömeke Katrin, Irniger Stefan, Grundmann Olav, Braus Gerhard H
Institute of Microbiology and Genetics, Georg-August-University, D-37077 Göttingen, Germany.
Eukaryot Cell. 2002 Oct;1(5):663-72. doi: 10.1128/EC.1.5.663-672.2002.
The c-Jun-like transcriptional activator Gcn4p controls biosynthesis of translational precursors in the yeast Saccharomyces cerevisiae. Protein stability is dependent on amino acid limitation and cis signals within Gcn4p which are recognized by cyclin-dependent protein kinases, including Pho85p. The Gcn4p population within unstarved yeast consists of a small relatively stable cytoplasmic fraction and a larger less stable nuclear fraction. Gcn4p contains two nuclear localization signals (NLS) which function independently of the presence or absence of amino acids. Expression of NLS-truncated Gcn4p results in an increased cytoplasmic fraction and an overall stabilization of the protein. The same effect is achieved for the entire Gcn4p in a yrb1 yeast mutant strain impaired in the nuclear import machinery. In the presence of amino acids, controlled destabilization of Gcn4p is triggered by the phosphorylation activity of Pho85p. A pho85delta mutation stabilizes Gcn4p without affecting nuclear import. Pho85p is localized within the nucleus in the presence or absence of amino acids. Therefore, there is a strict spatial separation of protein synthesis and degradation of Gcn4p in yeast. Control of protein stabilization which antagonizes Gcn4p function is restricted to the nucleus.
类c-Jun转录激活因子Gcn4p控制酿酒酵母中翻译前体的生物合成。蛋白质稳定性取决于氨基酸限制以及Gcn4p内被细胞周期蛋白依赖性蛋白激酶（包括Pho85p）识别的顺式信号。未饥饿酵母中的Gcn4p群体由一个相对稳定的小细胞质部分和一个不太稳定的大细胞核部分组成。Gcn4p包含两个核定位信号（NLS），其功能与氨基酸的存在与否无关。NLS截短的Gcn4p的表达导致细胞质部分增加和蛋白质的整体稳定。在核输入机制受损的yrb1酵母突变株中，整个Gcn4p也有同样的效果。在有氨基酸存在的情况下，Pho85p的磷酸化活性会引发Gcn4p的可控性降解。pho85δ突变使Gcn4p稳定，而不影响核输入。无论有无氨基酸，Pho85p都定位于细胞核内。因此，酵母中Gcn4p的蛋白质合成和降解存在严格的空间分隔。对抗Gcn4p功能的蛋白质稳定性控制仅限于细胞核。
