ArticleOncotarget2016
Inhibition of MARCH5 ubiquitin ligase abrogates MCL1-dependent resistance to BH3 mimetics via NOXA.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 44 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
- GET3 regulates apoptosis via tail-anchoring of MCL1.Cell death and differentiation · 2026Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- A new era in cancer therapy: targeting the Proteasome-Bcl-2 axis.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting the MARCH5-MFN2 axis to enhance mitochondrial fusion and sensitize multiple myeloma cells to venetoclax.Journal of translational medicine · 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
- MARCH5 Promotes the Progression of Thyroid cancer by Regulating Mitochondrial Autophagy Protein FUNDC1-mediated Pyroptosis.Applied biochemistry and biotechnology · 2025Article
- Role of MARCH E3 ubiquitin ligases in cancer development.Cancer metastasis reviews · 2024Review
- Mitochondria and cell death.Nature cell biology · 2024Review
- The UBE2J2/UBE2K-MARCH5 ubiquitination machinery regulates apoptosis in response to venetoclax in acute myeloid leukemia.Leukemia · 2024Article
- Role of the Mitochondrial E3 Ubiquitin Ligases as Possible Therapeutic Targets in Cancer Therapy.International journal of molecular sciences · 2023Review
- Death-seq identifies regulators of cell death and senolytic therapies.Cell metabolism · 2023Article
- Article
- Targeting a mitochondrial E3 ubiquitin ligase complex to overcome AML cell-intrinsic Venetoclax resistance.Leukemia · 2023Article
- Mitochondrial E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins.Cell death and differentiation · 2023Article
- MARCH5 regulates mitotic apoptosis through MCL1-dependent and independent mechanisms.Cell death and differentiation · 2023Article
- Article
- Transcriptional signatures of the BCL2 family for individualized acute myeloid leukaemia treatment.Genome medicine · 2022Article
- Deubiquitinases in cell death and inflammation.The Biochemical journal · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BH3 mimetic compounds induce tumor cell death through targeted inhibition of anti-apoptotic BCL2 proteins. Resistance to one such compound, ABT-737, is due to increased levels of anti-apoptotic MCL1. Using chemical and genetic approaches, we show that resistance to ABT-737 is abrogated by inhibition of the mitochondrial RING E3 ligase, MARCH5. Mechanistically, this is due to increased expression of pro-apoptotic BCL2 family member, NOXA, and is associated with MARCH5 regulation of MCL1 ubiquitylation and stability in a NOXA-dependent manner. MARCH5 expression contributed to an 8-gene signature that correlates with sensitivity to the preclinical BH3 mimetic, navitoclax. Furthermore, we observed a synthetic lethal interaction between MCL1 and MARCH5 in MCL1-dependent breast cancer cells. Our data uncover a novel level at which the BCL2 family is regulated; furthermore, they suggest targeting MARCH5-dependent signaling will be an effective strategy for treatment of BH3 mimetic-resistant tumors, even in the presence of high MCL1.
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.