Biosynthesis and alternate targeting of the lysosomal cysteine protease cathepsin L.

Upregulation of cathepsin L expression, whether during development or cell transformation, or mediated by ectopic expression from a plasmid, alters the targeting of the protease and thus its physiological function. Upregulated procathepsin L is targeted to small dense core vesicles and to the dense cores of multivesicular bodies, as well as to lysosomes and to the plasma membrane for selective secretion. The multivesicular vesicles resemble secretory lysosomes characterized in specialized cell types in that they are endosomes that stably store an upregulated protein and they possess the tetraspanin CD63.

Small molecule modulators of HIV Rev/Rev response element interaction identified by random screening.

A high throughput scintillation proximity assay with biotinylated human immunodeficiency virus (HIV) Rev protein and tritiated Rev response element RNA was used to screen over 500,000 small molecules. Several chemical classes of inhibitors and two chemical classes of enhancers of binding were identified, with the molecular weight range being 400-600. The most common structural motif of inhibitor was an acidic moiety at the end of a linear aromatic system.