一条识别脯氨酸并降解糖异生酶的N端规则途径。
An N-end rule pathway that recognizes proline and destroys gluconeogenic enzymes.
作者信息
Chen Shun-Jia, Wu Xia, Wadas Brandon, Oh Jang-Hyun, Varshavsky Alexander
机构信息
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Science. 2017 Jan 27;355(6323). doi: 10.1126/science.aal3655.
Abstract
Cells synthesize glucose if deprived of it, and destroy gluconeogenic enzymes upon return to glucose-replete conditions. We found that the Gid4 subunit of the ubiquitin ligase GID in the yeast Saccharomyces cerevisiae targeted the gluconeogenic enzymes Fbp1, Icl1, and Mdh2 for degradation. Gid4 recognized the N-terminal proline (Pro) residue and the ~5-residue-long adjacent sequence motifs. Pck1, the fourth gluconeogenic enzyme, contains Pro at position 2; Gid4 directly or indirectly recognized Pro at position 2 of Pck1, contributing to its targeting. These and related results identified Gid4 as the recognition component of the GID-based proteolytic system termed the Pro/N-end rule pathway. Substrates of this pathway include gluconeogenic enzymes that bear either the N-terminal Pro residue or a Pro at position 2, together with adjacent sequence motifs.
摘要
细胞在缺乏葡萄糖时会合成葡萄糖，并在恢复到葡萄糖充足的条件后破坏糖异生酶。我们发现，酿酒酵母中泛素连接酶GID的Gid4亚基靶向糖异生酶Fbp1、Icl1和Mdh2进行降解。Gid4识别N端脯氨酸（Pro）残基和~5个残基长的相邻序列基序。Pck1是第四种糖异生酶，在第2位含有Pro；Gid4直接或间接识别Pck1第2位的Pro，促进其靶向作用。这些及相关结果确定Gid4是基于GID的蛋白水解系统（称为Pro/N端规则途径）的识别成分。该途径的底物包括带有N端Pro残基或第2位Pro以及相邻序列基序的糖异生酶。
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