本所許家維老師研究團隊，解開細胞內蛋白質降解機制，成果發表於《Nature Communications》
The epidermal growth factor receptor (EGFR) plays critical roles in various cellular processes, such as cell growth and migration. An essential regulatory mechanism for inhibiting EGFR function involves its endocytic transport to the lysosome for protein degradation. Cargo adaptors recognize specific sorting motifs on cargo proteins for proper sorting steps. The dileucine-based sorting motif has been previously identified for the endosomal sorting of EGFR to the lysosome; however, the cargo adaptor recognizing the sorting motif remains unclear. In this study, we discovered that phosphoglycerate kinase 1 (PGK1) is recruited to the endosomal membrane upon phosphorylation, where PGK1 binds to the dileucine sorting motif on EGFR to facilitate the lysosomal transport. Furthermore, we elucidated two mechanisms operating together to promote PGK1 recruitment to the endosomal membrane: a lipid-based mechanism involving phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and a protein-based mechanism involving hepatocyte growth factor receptor substrate (Hrs). These findings suggest an unexpected role for a glycolytic enzyme and significantly contribute to the mechanistic understanding of EGFR transport to the lysosome.
本研究工作為許家維老師實驗室與美國哈佛醫學院Victor Hsu教授共同合作完成。其中最重要的執行者為本所博士班學生朱卲翎，協同作者亦為本所學生黃佳容、張育慈、姚舒云，計畫由國科會、教育部、臺大、及中央研究院共同支持下完成。
