Irniger Stefan, Braus Gerhard H
Institute of Microbiology and Genetics, Georg-August-University, Grisebachstrasse 8, 37077 Göttingen, Germany.
Curr Genet. 2003 Oct;44(1):8-18. doi: 10.1007/s00294-003-0422-3. Epub 2003 Jul 9.
The Gcn4 protein, a member of the AP-1 family of transcription factors, is involved in the expression of more than 500 genes in the budding yeast Saccharomyces cerevisiae. A key role of Gcn4p is the increased expression of many amino acid biosynthesis genes in response to amino acid starvation. The accumulation of this transcription activator is mainly induced by efficient translation of the GCN4 ORF and by stabilisation of the Gcn4 protein. Under normal growth conditions, Gcn4p is a highly unstable protein, thereby resembling many eukaryotic transcription factors, including mammalian Jun and Myc proteins. Gcn4p is degraded by ubiquitin-dependent proteolysis mediated by the Skp1/cullin/F-box (SCF) ubiquitin ligase, which recognises specifically phosphorylated substrates. Two cyclin-dependent protein kinases, Pho85p and Srb10p, have crucial functions in regulating Gcn4p phosphorylation and degradation. The past few years have revealed many novel insights into these regulatory processes. Here, we summarise current knowledge about the factors and mechanisms regulating Gcn4p stability.
Gcn4蛋白是转录因子AP-1家族的成员之一，参与了出芽酵母酿酒酵母中500多个基因的表达。Gcn4p的一个关键作用是在氨基酸饥饿时增加许多氨基酸生物合成基因的表达。这种转录激活因子的积累主要是由GCN4开放阅读框的有效翻译和Gcn4蛋白的稳定化诱导的。在正常生长条件下，Gcn4p是一种高度不稳定的蛋白，因此与许多真核转录因子相似，包括哺乳动物的Jun和Myc蛋白。Gcn4p通过Skp1/ 类cullin蛋白/F-盒（SCF）泛素连接酶介导的泛素依赖性蛋白水解作用被降解，该连接酶特异性识别磷酸化底物。两种细胞周期蛋白依赖性蛋白激酶Pho85p和Srb10p在调节Gcn4p的磷酸化和降解中具有关键作用。过去几年揭示了许多关于这些调节过程的新见解。在这里，我们总结了目前关于调节Gcn4p稳定性的因素和机制的知识。
