ArticleBMC cancer2018
MAFb protein confers intrinsic resistance to proteasome inhibitors in multiple myeloma.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Multiple myeloma: A tale of deregulated transcription factors.HemaSphere · 2026Review
- Hi-C for genome-wide detection of enhancer-hijacking rearrangements in routine lymphoid cancer biopsies.Cell genomics · 2026Article
- Saga of MCL1 inhibitors in multiple myeloma.Biochemical pharmacology · 2026Review
- Post-Translational Modifications in Multiple Myeloma: Mechanisms of Drug Resistance and Therapeutic Opportunities.Biomolecules · 2025Review
- Identifying Genes Associated with the Anticancer Activity of a Fluorinated Chalcone in Triple-Negative Breast Cancer Cells Using Bioinformatics Tools.International journal of molecular sciences · 2025Article
- TRIM44, a Novel Prognostic Marker, Supports the Survival of Proteasome-Resistant Multiple Myeloma Cells.Cells · 2024Article
- Evaluation of Genes and Molecular Pathways Involved in the Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma: A Systems Biology Approach.Molecular biotechnology · 2023Article
- Hypoxia-induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase-1 in multiple myeloma.Cancer medicine · 2023Article
- The role and regulation of Maf proteins in cancer.Biomarker research · 2023Review
- KLF17 is an important regulatory component of the transcriptomic response of Atlantic salmon macrophages toFrontiers in immunology · 2023Article
- Article
- β adrenergic signaling regulates hematopoietic stem and progenitor cell commitment and therapy sensitivity in multiple myeloma.Haematologica · 2022Article
- Review
- GPBAR1 promotes proliferation and is related to poor prognosis of high-grade glioma via inducing MAFB expression.Histology and histopathology · 2022Article
- Prognostic Value of Resistance Proteins in Plasma Cells from Multiple Myeloma Patients Treated with Bortezomib-Based Regimens.Journal of clinical medicine · 2021Article
- The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology.Cancers · 2021Review
- Review
- Review
- Machine Learning Applicability for Classification of PAD/VCD Chemotherapy Response Using 53 Multiple Myeloma RNA Sequencing Profiles.Frontiers in oncology · 2021Article
- High expression of chaperonin-containing TCP1 subunit 3 may induce dismal prognosis in multiple myeloma.The pharmacogenomics journal · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMultiple myeloma (MM) patients with t(14;20) have a poor prognosis and their outcome has not improved following the introduction of bortezomib (Bzb). The mechanism underlying the resistance to proteasome inhibitors (PIs) for this subset of patients is unknown.
methodsIC50 of Bzb and carfilzomib (CFZ) in human myeloma cell lines (HMCLs) were established by MTT assay. Gene Expression profile (GEP) analysis was used to determine gene expression in primary myeloma cells. Immunoblotting analysis was performed for MAFb and caspase family proteins. Immunofluorescence staining was used to detect the location of MAFb protein in MM cells. Lentiviral infections were used to knock-down MAFb expression in two lines. Apoptosis detection by flow cytometry and western blot analysis was performed to determine the molecular mechanism MAFb confers resistance to proteasome inhibitors.
resultsWe found high levels of MAFb protein in cell lines with t(14;20), in one line with t(6;20), in one with Igλ insertion into MAFb locus, and in primary plasma cells from MM patients with t(14;20). High MAFb protein levels correlated with higher IC50s of PIs in MM cells. Inhibition of GSK3β activity or treatment with Bzb or CFZ prevented MAFb protein degradation without affecting the corresponding mRNA level indicating a role for GSK3 and proteasome inhibitors in regulation of MAFb stability. Silencing MAFb restored sensitivity to Bzb and CFZ, and enhanced PIs-induced apoptosis and activation of caspase-3, - 8, - 9, PARP and lamin A/C suggesting that high expression of MAFb protein leads to insensitivity to proteasome inhibitors.
conclusionThese results highlight the role of post-translational modification of MAFb in maintaining its protein level, and identify a mechanism by which proteasome inhibitors induced stabilization of MAFb confers resistance to proteasome inhibitors, and provide a rationale for the development of targeted therapeutic strategies for this subset of patients.
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