PEPTIDE SEQUENCES THAT TARGET PROTEINS FOR LYSOSOMAL DEGRADATION

It may be possible to design novel drug targeting strategies based on pathways by which cells target proteins to particular intracellular organelles. Cells use information in the structure of a protein in order to target it to its proper intracellular location. There is growing evidence that structural features of proteins also target them for particular degradative pathways within cells. Our focus of attention is a lysosomal pathway of proteolysis that is selective for a particular group of cytosolic proteins. This pathway is activated when cells in culture are deprived of serum or when whole animals are starved, and proteins that enter lysosomes by this pathway contain peptide sequences related to Lys-Phe-Glu-Arg-Gln (KFERQ). Our recent evidence suggests that the pathway by which such proteins enter lysosomes for destruction involves the binding of a heat-shock 70 kDa-related protein to the KFERQ peptide region. © 1990.