{"entity":{"id":"proteasome","kind":"target","name":"Proteasome (PSMB5)","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Proteasome","links":[{"label":"UniProt P28074: PSMB5","url":"https://www.uniprot.org/uniprotkb/P28074/entry"}],"tags":[],"related":[],"cancers":["multiple-myeloma","mantle-cell-lymphoma"],"sections":[],"technologies":[],"targets":[],"drugs":["bortezomib","carfilzomib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"PSMB5","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas PSMB5 tissue","url":"https://www.proteinatlas.org/ENSG00000100804-PSMB5/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000100804 associations","url":"https://platform.opentargets.org/target/ENSG00000100804/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:9542","ensembl":"ENSG00000100804","uniprot":"P28074","entrez":"5693","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"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)\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2306472/","biology":"Multi-subunit protease complex that degrades ubiquitinated proteins; PSMB5 carries the chymotrypsin-like catalytic activity targeted by approved inhibitors.","whereFound":["Multiple myeloma","Mantle cell lymphoma"],"targetClass":"enzyme","prevalence":[{"cancerId":"metastatic-cancer","pct":"all","measure":"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."}]},"route":"/targets/proteasome/","neighbours":{"cancer":[{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-transplant-eligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-eligible","route":"/cancers/myeloma-transplant-eligible/"},{"id":"myeloma-transplant-ineligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-ineligible","route":"/cancers/myeloma-transplant-ineligible/"},{"id":"plasma-cell-leukaemia","kind":"cancer","name":"Plasma cell leukaemia","route":"/cancers/plasma-cell-leukaemia/"}],"drug":[{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"carfilzomib","kind":"drug","name":"Carfilzomib","route":"/drugs/carfilzomib/"}]}}