ArticleCell death & disease2019
A novel UCHL
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- ZUP1 promotes DNA repair and immune evasion to drive olaparib resistance in triple-negative breast cancer.Journal of advanced research · 2026Article
- UCHL3 Promotes Triple-Negative Breast Cancer Metastatic Potential Through Enhancing Cell Migration and Invasion.Applied biochemistry and biotechnology · 2026Article
- UCHL3 depletion inhibits gastric cancer progression and enhances palbociclib sensitivity by regulating the AKT/CCND1 signaling axis via ENO1 ubiquitination.Cell death & disease · 2025Article
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- The FSIP Family: Roles in Health and Cancer.Cancers · 2025Review
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
- Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development.Current oncology (Toronto, Ont.) · 2025Review
- Targeting the JAK2-STAT3-UCHL3-ENO1 axis suppresses glycolysis and enhances the sensitivity to 5-FU chemotherapy inActa pharmaceutica Sinica. B · 2025Article
- DNA damage response in breast cancer and its significant role in guiding novel precise therapies.Biomarker research · 2024Review
- Breast Cancer Stem Cells and Tumor Heterogeneity: Characteristics and Therapeutic Strategies.Cancers · 2024Review
- OTUD7B knockdown inhibits the proliferation and stemness of breast cancer cells by destabilizing FOXM1.Oncology letters · 2024Article
- Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.American journal of cancer research · 2024Review
- Mitochondrial Functionality Is Regulated by Alkylphospholipids in Human Colon Cancer Cells.Biology · 2023Article
- Farrerol directly activates the deubiqutinase UCHL3 to promote DNA repair and reprogramming when mediated by somatic cell nuclear transfer.Nature communications · 2023Article
- Interfering with the Ubiquitin-Mediated Regulation of Akt as a Strategy for Cancer Treatment.International journal of molecular sciences · 2023Review
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells.Journal of cellular and molecular medicine · 2023Article
- Structural Insights into the Phosphorylation-Enhanced Deubiquitinating Activity of UCHL3 and Ubiquitin Chain Cleavage Preference Analysis.International journal of molecular sciences · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) treatment remains a great challenge for clinical practice and novel therapeutic strategies are urgently needed. UCHL3 is a deubiquitinase that is overexpressed in TNBC and correlates with poor prognosis. UCHL3 deubiquitinates RAD51 thereby promoting the recruitment of RAD51 to DNA damage sites and augmenting DNA repair. Therefore, UCHL3 overexpression can render cancer cells resistant to DNA damage inducing chemo and radiotherapy, and targeting UCHL3 can sensitize TNBC to radiation and chemotherapy. However, small molecule inhibitors of UCHL3 are yet to be identified. Here we report that perifosine, a previously reported Akt inhibitor, can inhibit UCHL3 in vitro and in vivo. We found low dose (50 nM) perifosine inhibited UCHL3 deubiquitination activity without affecting Akt activity. Furthermore, perifosine enhanced Olaparib-induced growth inhibition in TNBC cells. Mechanistically, perifosine induced RAD51 ubiquitination and blocked the RAD51-BRCA2 interaction, which in turn decreased ionizing radiation-induced foci (IRIF) of Rad51 and, thereby, homologous recombination (HR)-mediated DNA double strand break repair. In addition, combination of perifosine and Olaparib showed synergistic antitumor activity in vivo in TNBC xenograft model. Thus, our present study provides a novel therapeutic approach to optimize PARP inhibitor treatment efficiency.
Indexed as
Identifiers
What OpenQuestion holds
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.