细胞外
溶酶体
细胞生物学
内体
蛋白质降解
蛋白质水解
胞浆
膜蛋白
生物
受体
转运蛋白
胞外囊泡
细胞内
内吞作用
降级(电信)
内化
自噬
化学
内吞循环
生物化学
高尔基体
分泌物
膜
微泡
酶
基因
小RNA
作者
Green Ahn,Steven M. Banik,Carolyn R. Bertozzi
标识
DOI:10.1016/j.chembiol.2021.02.024
摘要
Targeted protein degradation (TPD) is a promising strategy to remove deleterious proteins for therapeutic benefit and to probe biological pathways. The past two decades have witnessed a surge in the development of technologies that rely on intracellular machinery to degrade challenging cytosolic targets. However, these TPD platforms leave the majority of extracellular and membrane proteins untouched. To enable degradation of these classes of proteins, internalizing receptors can be co-opted to traffic extracellular proteins to the lysosome. Sweeping antibodies and Seldegs use Fc receptors in conjunction with engineered antibodies to degrade soluble proteins. Recently, lysosome-targeting chimeras (LYTACs) have emerged as a strategy to degrade both secreted and membrane-anchored targets. Together with other newcomer technologies, including antibody-based proteolysis-targeting chimeras, modalities that degrade extracellular proteins have promising translational potential. This perspective will give an overview of TPD platforms that degrade proteins via outside-in approaches and focus on the recent development of LYTACs.
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