Within and beyond the boundaries of proteasomal assembly: PSMD9 chaperone as a multifunctional protein

PSMD9/Nas2/Bridge-1 is one of the assembly chaperones of the 19S regulatory particle of the eukaryotic proteasome. While this is among PSMD9's well-recognized roles, the role of PSMD9 in cancer proteasome assembly/disassembly and activity, as a key factor in the ubiquitination and degradation of proteins by the proteasome, unfolded protein response, and proteostasis, nucleolar organization, are some of the recent findings. Several unbiased screening, high-throughput studies, genome-wide association studies (GWAS) have found surprising associations and potential roles for PSMD9 in a variety of diseases or conditions. Although in a majority of these cases the mechanism remains unclear, it is important to take note that this multi-functional protein, in the absence of any enzymatic role, relies primarily on its ability to interact with other proteins and biomolecules in the cells. A surprising range of proteins that associate with PSMD9 discovered by the structure-guided approaches overlaps with many different functions associated with this protein or the proteasome in literature. Collective evidence also points to the possibility that PSMD9 could be an Achilles' heel in some of the solid cancers.