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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.
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.
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.
Multi-subunit protease complex that degrades ubiquitinated proteins; PSMB5 carries the chymotrypsin-like catalytic activity targeted by approved inhibitors.
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.
Broadly expressed or essential: HPA lists PSMB5 among essential proteins and finds the RNA at low tissue specificity; the 2 medicines aimed at it (Bortezomib, Carfilzomib) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA PSMB5: RNA low tissue specificity; high antibody staining in 3 normal tissues. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Multiple myeloma, Lymphoma); Open Targets associates it with 2 specific cancer types at or above 0.5 (plasma cell myeloma, mantle cell lymphoma). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas PSMB5 tissue; Open Targets ENSG00000100804 associations
First described 1990. Earliest sequence paper UniProt cites for the protein: Lee L.W. et al, Biochim. Biophys. Acta, 1990, "Relationships among the subunits of the high molecular weight proteinase, macropain (proteasome)". Source.
Multi-subunit protease complex that degrades ubiquitinated proteins; PSMB5 carries the chymotrypsin-like catalytic activity targeted by approved inhibitors.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Caudate, Cerebral cortex, Fallopian tube, Kidney, Nasopharynx, Pancreas, Parathyroid gland.
No cancer stained high; medium in carcinoid, glioma, thyroid cancer.
HPA PSMB5 tissue · HPA PSMB5 pathology · HPA protein class: Essential proteins, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Metastatic cancer | all% | Housekeeping enzyme present in every dividing cell (protein disposal, on which myeloma cells depend most); not a selection marker, which is why these drugs are given by cancer type rather than by test. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"Proteasome" OR ABSTRACT:"Proteasome" OR TITLE:"PSMB5" OR ABSTRACT:"PSMB5") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Proteasome (PSMB5), not a curated reading list.
Shares Newly diagnosed multiple myeloma, transplant-ineligible, Plasma cell leukaemia, Newly diagnosed multiple myeloma, transplant-eligible, Bortezomib.
Shares Carfilzomib, Bortezomib, Multiple myeloma.
Shares Plasma cell leukaemia, Newly diagnosed multiple myeloma, transplant-eligible.
Shares Carfilzomib, Bortezomib, Multiple myeloma.
Shares Carfilzomib, Bortezomib, Multiple myeloma.
Shares Newly diagnosed multiple myeloma, transplant-ineligible, Newly diagnosed multiple myeloma, transplant-eligible, Multiple myeloma.
Shares Carfilzomib, Bortezomib, Multiple myeloma.
Shares Plasma cell leukaemia, Newly diagnosed multiple myeloma, transplant-eligible, Multiple myeloma.