targetsTarget

Proteasome (PSMB5)

The cell's protein shredder. Myeloma cells make huge amounts of antibody protein and depend on the proteasome to clear the waste, so blocking it kills them.

The 26S proteasome degrades ubiquitin-tagged proteins, and its chymotrypsin-like activity sits in the PSMB5 subunit that bortezomib and carfilzomib bind. Plasma cells, and myeloma cells in particular, secrete immunoglobulin at a rate that overloads protein quality control, so proteasome inhibition triggers a terminal unfolded protein response and blocks NF-kB signalling. Bortezomib was approved for myeloma in 2003 and carfilzomib in 2012; peripheral neuropathy is the class toxicity of bortezomib and cardiovascular events of carfilzomib.

Proteasome (PSMB5): what it is and how drugs act on it · animated generic schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · The cell's protein shredder. Myeloma cells make huge amounts of antibody protein and depend on the proteasome to clear the waste, so blocking it kills them.

1 · What it is
The cell's protein shredder. Myeloma cells make huge amounts of antibody protein and depend on the proteasome to clear the waste, so blocking it kills them.
2 · What goes wrong in cancer
Multi-subunit protease complex that degrades ubiquitinated proteins; PSMB5 carries the chymotrypsin-like catalytic activity targeted by approved inhibitors.
3 · How drugs use it
No product in this corpus aims at Proteasome (PSMB5) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.

Full dossier: hotspots, trials, resistance, assays, models, open questions →

External identifiers

PSMB5HGNCEnsemblUniProtAlphaFold DBOpen TargetsCIViCOncoKBCOSMICcBioPortalDepMapHuman Protein AtlasNCBI Gene

Biology

Multi-subunit protease complex that degrades ubiquitinated proteins; PSMB5 carries the chymotrypsin-like catalytic activity targeted by approved inhibitors.

Where it is found