ArticleeLife2020
MARCH5 mediates NOXA-dependent MCL1 degradation driven by kinase inhibitors and integrated stress response activation.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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
40 citing papers in PubMed, 62 citations in OpenAlex.
- The mitochondrial ubiquitin ligase MARCHF5 cooperates with MCL1 to inhibit apoptosis in KSHV-transformed primary effusion lymphoma cell lines.PLoS pathogens · 2026Article
- Review
- Stress-activated pathways mediate PFAS effects on human placental syncytiotrophoblast cells.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Revealing the Binding Mechanism of Gossypol on Bcl‑2 via Funnel Metadynamics Simulations.ACS omega · 2026Article
- CDK4/6 inhibition overcomes venetoclax resistance mechanisms with enhanced combination activity in acute myeloid leukemia.Cell reports. Medicine · 2026Article
- Mitotic errors as triggers of cell death and inflammation.Nature cell biology · 2026Review
- Developing therapeutic strategies to target MCL1 and BCLXL in lethal prostate cancer.iScience · 2025Article
- Deacetylation of ACLY Mediates RNA MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cul5bioRxiv : the preprint server for biology · 2025Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- MCL-1 as a molecular switch between myofibroblastic and pro-angiogenic features of breast cancer-associated fibroblasts.Cell death & disease · 2025Article
- Targeting the WSB2-NOXA axis in cancer cells for enhanced sensitivity to BCL-2 family protein inhibitors.eLife · 2025Article
- BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress.Nature communications · 2025Article
- Narciclasine enhances cisplatin-induced apoptotic cell death by inducing unfolded protein response-mediated regulation of NOXA and MCL1.Cellular & molecular biology letters · 2025Article
- Outer mitochondrial membrane E3 Ub ligase MARCH5 controls de novo peroxisome biogenesis.Developmental cell · 2025Article
- PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.Nature communications · 2025Article
- Mitochondrial involvement in PC: improving therapeutic strategies.Frontiers in pharmacology · 2025Review
- Cellular senescence in metastatic prostate cancer: A therapeutic opportunity or challenge (Review).Molecular medicine reports · 2024Review
- Article
- BioE3 identifies specific substrates of ubiquitin E3 ligases.Nature communications · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
MCL1 has critical antiapoptotic functions and its levels are tightly regulated by ubiquitylation and degradation, but mechanisms that drive this degradation, particularly in solid tumors, remain to be established. We show here in prostate cancer cells that increased NOXA, mediated by kinase inhibitor activation of an integrated stress response, drives the degradation of MCL1, and identify the mitochondria-associated ubiquitin ligase MARCH5 as the primary mediator of this NOXA-dependent MCL1 degradation. Therapies that enhance MARCH5-mediated MCL1 degradation markedly enhance apoptosis in response to a BH3 mimetic agent targeting BCLXL, which may provide for a broadly effective therapy in solid tumors. Conversely, increased MCL1 in response to MARCH5 loss does not strongly sensitize to BH3 mimetic drugs targeting MCL1, but instead also sensitizes to BCLXL inhibition, revealing a codependence between MARCH5 and MCL1 that may also be exploited in tumors with
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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.