ArticleOncogene2020
The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- c-Myc: an emerging participant in heart failure.Frontiers in cardiovascular medicine · 2026Review
- A propensity score matching study on clinical characteristics and risk factors of herpes zoster in malignant tumor.Frontiers in oncology · 2026Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- Inhibition of tumor growth using A conjugated nanobody that specifically targets c-MYC.Oncogene · 2025Article
- Directly targeting G-quadruplexes contributes to the anti-multiple myeloma efficacy of Epimedokoreanin B.Acta biochimica et biophysica Sinica · 2025Article
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- Regulatory role of E3 ubiquitin ligases in multiple myeloma: from molecular mechanisms to therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- The NF-κB Pharmacopeia: Novel Strategies to Subdue an Intractable Target.Biomedicines · 2022Review
- A novel protein encoded by circHNRNPU promotes multiple myeloma progression by regulating the bone marrow microenvironment and alternative splicing.Journal of experimental & clinical cancer research : CR · 2022Article
- CRISPR screening of E3 ubiquitin ligases reveals Ring Finger Protein 185 as a novel tumor suppressor in glioblastoma repressed by promoter hypermethylation and miR-587.Journal of translational medicine · 2022Article
- The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases.Frontiers in cellular and infection microbiology · 2022Review
- Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation.Molecules (Basel, Switzerland) · 2021Review
- The long journey to bring a Myc inhibitor to the clinic.The Journal of cell biology · 2021Review
- The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer.Biomedicines · 2021Review
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Modular network mechanism of CCN1-associated resistance to HSV-1-derived oncolytic immunovirotherapies for glioblastomas.Scientific reports · 2021Article
- Targeting RFWD2 as an Effective Strategy to Inhibit Cellular Proliferation and Overcome Drug Resistance to Proteasome Inhibitor in Multiple Myeloma.Frontiers in cell and developmental biology · 2021Article
- Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Proteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM. We identified elevated expression of HUWE1 in MM compared with normal cells. Small molecule-mediated inhibition of HUWE1 resulted in growth arrest of MM cell lines without significantly effecting the growth of normal bone marrow cells, suggesting a favorable therapeutic index. Studies using a HUWE1 knockdown model showed similar growth inhibition. HUWE1 expression positively correlated with MYC expression in MM bone marrow cells and correspondingly, genetic knockdown and biochemical inhibition of HUWE1 reduced MYC expression in MM cell lines. Proteomic identification of HUWE1 substrates revealed a strong association of HUWE1 with metabolic processes in MM cells. Intracellular glutamine levels are decreased in the absence of HUWE1 and may contribute to MYC degradation. Finally, HUWE1 depletion in combination with lenalidomide resulted in synergistic anti-MM activity in both in vitro and in vivo models. Taken together, our data demonstrate an important role of HUWE1 in MM cell growth and provides preclinical rationale for therapeutic strategies targeting HUWE1 in MM.
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