Ubiquitin Specific Peptidase 20 (USP20)

The de-ubiquitinating enzymes USP33 and USP20 are recruited to the β2AR complexes, by using cellular co-immunoprecipitation assays. USP33 and USP20 could function to reverse β2AR ubiquitination and thus, could be involved in the regulation of receptor trafficking. Indeed, coexpression of the β2AR with USP33 or USP20 (USP33/20) results in a dramatic reduction of isoproterenol-stimulated ubiquitination of the receptor.

In contrast, similar coexpression of catalytically inactive USP33/20 mutants, which retains receptor binding, does not lead to any decrease in receptor ubiquitination. When HEK-293 cells expressing the β2AR are exposed to 10 μm isoproterenol for 6h, internalized β2ARs are found to colocalize with the lysosomal marker protein, LAMP2.