ArticleOncotarget2015
UCHL1 is a biomarker of aggressive multiple myeloma required for disease progression.
Article in Oncotarget, 2015. 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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The trial behind it
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Review
- Disrupting USP39 deubiquitinase function impairs the survival and migration of multiple myeloma cells through ZEB1 degradation.Journal of experimental & clinical cancer research : CR · 2024Article
- The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.Nature cancer · 2024Article
- Ubiquitin C‑terminal hydrolase‑L1: A new cancer marker and therapeutic target with dual effects (Review).Oncology letters · 2023Review
- Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases.International journal of molecular sciences · 2022Review
- Deubiquitylase USP12 induces pro-survival autophagy and bortezomib resistance in multiple myeloma by stabilizing HMGB1.Oncogene · 2022Article
- Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma.Nature communications · 2021Article
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- Optimization and Anti-Cancer Properties of Fluoromethylketones as Covalent Inhibitors for Ubiquitin C-Terminal Hydrolase L1.Molecules (Basel, Switzerland) · 2021Article
- TargetingPathology oncology research : POR · 2021Article
- Review
- Ubiquitin C-Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor.Chembiochem : a European journal of chemical biology · 2020Article
- Ubiquitin C-terminal hydrolase-L1 has prognostic relevance and is a therapeutic target for high-grade neuroendocrine lung cancers.Cancer science · 2020Article
- Gene Expression Profiling of B Cell Lymphoma in Dogs Reveals Dichotomous Metabolic Signatures Distinguished by Oxidative Phosphorylation.Frontiers in oncology · 2020Article
- DUBbing Down Translation: The Functional Interaction of Deubiquitinases with the Translational Machinery.Molecular cancer therapeutics · 2019Review
- Involvement of E3 Ligases and Deubiquitinases in the Control of HIF-α Subunit Abundance.Cells · 2019Review
- Review
- A cysteine near the C-terminus of UCH-L1 is dispensable for catalytic activity but is required to promote AKT phosphorylation, eIF4F assembly, and malignant B-cell survival.Cell death discovery · 2019Article
- Concentration of Proteasome in the Blood Plasma of Children with Acute Appendicitis, Before and After Surgery, and Its Correlation with CRP.World journal of surgery · 2018Article
- Gene-expression signature regulated by the KEAP1-NRF2-CUL3 axis is associated with a poor prognosis in head and neck squamous cell cancer.BMC cancer · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The success of proteasome inhibition in multiple myeloma highlights the critical role for the ubiquitin-proteasome system (UPS) in this disease. However, there has been little progress in finding more specific targets within the UPS involved in myeloma pathogenesis. We previously found the ubiquitin hydrolase UCH-L1 to be frequently over-expressed in B-cell malignancies, including myeloma, and showed it to be a potent oncogene in mice. Here we show that UCH-L1 is a poor prognostic factor that is essential for the progression of myeloma. We found high levels of UCHL1 to predict early progression in newly diagnosed patients; a finding reversed by the inclusion of bortezomib. We also found high UCHL1 levels to be a critical factor in the superiority of bortezomib over high-dose dexamethasone in relapsed patients. High UCHL1 partially overlaps with, but is distinct from, known genetic risks including 4p16 rearrangement and 1q21 amplification. Using an orthotopic mouse model, we found UCH-L1 depletion delays myeloma dissemination and causes regression of established disease. We conclude that UCH-L1 is a biomarker of aggressive myeloma that may be an important marker of bortezomib response, and may itself be an effective target in disseminated disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.