Lysosome-targeting chimeras containing an endocytic signaling motif trigger endocytosis and lysosomal degradation of cell-surface proteins.

ABSTRACT: Lysosome-targeting degradation technologies have emerged as a promising therapeutic strategy for the selective depletion of target extracellular and cell-surface proteins by harnessing a cell-surface effector protein such as lysosome-targeting receptors (LTRs) or transmembrane E3 ligases that direct lysosomal degradation. We recently developed a lysosome-targeting degradation platform termed signal-mediated lysosome-targeting chimeras (SignalTACs) that functions independently of an LTR or E3 ligase; these are engineered fusion proteins comprising a target binder, a cell-penetrating peptide (CPP), and a lysosomal sorting signal motif (P1). Herein, we present the next-generation SignalTACs containing a single endocytic signal that bypasses the need for a CPP. We demonstrate that the fusion w

SUBMITTER: Fang T 

PROVIDER: S-EPMC11459673 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature