Xie Y, Varshavsky A
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3056-61. doi: 10.1073/pnas.071022298.
The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required for normal levels of intracellular proteolysis. RPN4 is a transcriptional activator of genes encoding proteasomal subunits. Here we show that RPN4 is required for normal levels of these subunits. Further, we demonstrate that RPN4 is extremely short-lived (t(1/2) approximately 2 min), that it directly interacts with RPN2, a subunit of the 26S proteasome, and that rpn4Delta cells are perturbed in their cell cycle. The degradation signal of RPN4 was mapped to its N-terminal region, outside the transcription-activation domains of RPN4. The ability of RPN4 to augment the synthesis of proteasomal subunits while being metabolically unstable yields a negative feedback circuit in which the same protein up-regulates the proteasome production and is destroyed by the assembled active proteasome.
酿酒酵母的RPN4（SON1，UFD5）蛋白是细胞内正常水平蛋白质水解所必需的。RPN4是编码蛋白酶体亚基的基因的转录激活因子。在此我们表明这些亚基的正常水平需要RPN4。此外，我们证明RPN4寿命极短（半衰期约2分钟），它直接与26S蛋白酶体的一个亚基RPN2相互作用，并且rpn4Δ细胞的细胞周期受到干扰。RPN4的降解信号定位于其N端区域，在RPN4的转录激活域之外。RPN4在代谢不稳定的情况下增强蛋白酶体亚基合成的能力产生了一个负反馈回路，其中同一蛋白质上调蛋白酶体的产生并被组装好的活性蛋白酶体破坏。
