ArticleeLife2019
The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Preclinical Anticipation of On- and Off-Target Resistance Mechanisms to Anti-Cancer Drugs: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- mTORC1 activity suppresses ferroptosis through a SCARB1-dependent HDL-tocopherol uptake pathway.Molecular cell · 2026Article
- Revealing the Binding Mechanism of Gossypol on Bcl‑2 via Funnel Metadynamics Simulations.ACS omega · 2026Article
- CUL5 E3 ubiquitin ligase regulates the evasion of bladder cancer cells to CD8+ T cell-mediated killing by inhibiting autophagy.PLoS biology · 2026Article
- CUL5-mediated ubiquitination in cancer cell therapy: context-dependent roles, molecular networks, and emerging therapeutic avenues.Frontiers in medicine · 2026Review
- The Crosstalk Between CRL5 and APC/C E3 Ligases Regulates Metastasis and Chemosensitivity of Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- Cul5bioRxiv : the preprint server for biology · 2025Article
- Protein neddylation in lung tumorigenesis: Target validation and targeted therapy.Fundamental research · 2025Review
- Targeting the WSB2-NOXA axis in cancer cells for enhanced sensitivity to BCL-2 family protein inhibitors.eLife · 2025Article
- Predicting and overcoming resistance to CDK9 inhibitors for cancer therapy.Acta pharmaceutica Sinica. B · 2023Article
- NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.Cell death discovery · 2023Review
- Genome-wide CRISPR/Cas9 screening for drug resistance in tumors.Frontiers in pharmacology · 2023Review
- Applications of CRISPR screening to lung cancer treatment.Frontiers in cell and developmental biology · 2023Review
- MCL-1 is a clinically targetable vulnerability in breast cancer.Cell cycle (Georgetown, Tex.) · 2022Review
- Characterization of a prognostic model for lung squamous cell carcinoma based on eight stemness index-related genes.BMC pulmonary medicine · 2022Article
- RNF7 inhibits apoptosis and sunitinib sensitivity and promotes glycolysis in renal cell carcinoma via the SOCS1/JAK/STAT3 feedback loop.Cellular & molecular biology letters · 2022Article
- A new era in functional genomics screens.Nature reviews. Genetics · 2022Review
- Cullin-5 (CUL5) as a potential prognostic marker in a pan-cancer analysis of human tumors.Bioengineered · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Overexpression of anti-apoptotic proteins MCL1 and Bcl-xL are frequently observed in many cancers. Inhibitors targeting MCL1 are in clinical development, however numerous cancer models are intrinsically resistant to this approach. To discover mechanisms underlying resistance to MCL1 inhibition, we performed multiple flow-cytometry based genome-wide CRISPR screens interrogating two drugs that directly (MCL1i) or indirectly (CDK9i) target MCL1. Remarkably, both screens identified three components (CUL5, RNF7 and UBE2F) of a cullin-RING ubiquitin ligase complex (CRL5) that resensitized cells to MCL1 inhibition. We find that levels of the BH3-only pro-apoptotic proteins Bim and Noxa are proteasomally regulated by the CRL5 complex. Accumulation of Noxa caused by depletion of CRL5 components was responsible for re-sensitization to CDK9 inhibitor, but not MCL1 inhibitor. Discovery of a novel role of CRL5 in apoptosis and resistance to multiple types of anticancer agents suggests the potential to improve combination treatments.
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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.