ArticleCell death & disease2017
Inhibition of the deubiquitinase USP5 leads to c-Maf protein degradation and myeloma cell apoptosis.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 86 citations in OpenAlex.
- Allantopyrone A promotes cross-linking of ubiquitin-specific protease 5 (USP5) and inhibits its deubiquitinase activity by targeting distinct domains.The Journal of antibiotics · 2026Article
- UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.Clinical and experimental medicine · 2026Review
- USP5 in cancer: a therapeutic window into metabolism and drug resistance.Journal of translational medicine · 2026Review
- USP5 inhibition stimulates immunogenic ferroptosis that enhances immunotherapy in diffuse large B-cell lymphoma.Cell communication and signaling : CCS · 2026Article
- USP5-induced deubiquitination of P4HB alleviates ER stress-mediated apoptosis in intestinal ischemia/reperfusion.Cellular and molecular life sciences : CMLS · 2025Article
- MAFB: a key regulator of myeloid commitment involved in hematological diseases.Cell death discovery · 2025Review
- USP5 motivates immunosuppressive microenvironment in multiple myeloma by activating STAT2-PFKFB4-mediated glycolysis.Cancer immunology, immunotherapy : CII · 2025Article
- mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation.Cell reports · 2025Article
- Review
- DUBs in Alzheimer's disease: mechanisms and therapeutic implications.Cell death discovery · 2024Review
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Unraveling the Immune Regulatory Functions of USP5: Implications for Disease Therapy.Biomolecules · 2024Review
- USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.Cell death & disease · 2024Article
- Ubiquitin-specific protease 5 promotes bladder cancer progression through stabilizing Twist1.Oncogene · 2024Article
- Bruceine B Displays Potent Antimyeloma Activity by Inducing the Degradation of the Transcription Factor c-Maf.ACS pharmacology & translational science · 2024Article
- Unraveling the Mechanism of Action of Ubiquitin-Specific Protease 5 and Its Inhibitors in Tumors.Clinical Medicine Insights. Oncology · 2024Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Article
- The role and regulation of Maf proteins in cancer.Biomarker research · 2023Review
- EOAI, a ubiquitin-specific peptidase 5 inhibitor, prevents non-small cell lung cancer progression by inducing DNA damage.BMC cancer · 2023Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability. Notably, MafA and MafB are also members of the c-Maf family, however, USP5 failed to deubiquitinate MafA, suggesting its substrate specificity. In the functional studies, USP5 was found to promoted the transcriptional activity of c-Maf. Consistent with the high level of c-Maf protein in MM cells, USP5 was also highly expressed. When USP5 was knocked down, c-Maf underwent degradation. Interestingly, USP5 silence led to apoptosis of MM cells expressing c-Maf but not MM cells lacking c-Maf, indicating c-Maf is a key factor in USP5-mediated MM cell proliferation and survival. Consistent with this finding, WP1130, an inhibitor of several Dubs including USP5, suppressed the transcriptional activity of c-Maf and induced MM cell apoptosis. When c-Maf was overexpressed, WP1130-induced MM cell apoptosis was abolished. Taken together, these findings suggest that USP5 regulates c-Maf stability and MM cell survival. Targeting the USP5/c-Maf axis could be a potential strategy for MM treatment.
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