ArticleFrontiers in oncology2012
The splicing mutant of the human tumor suppressor protein DFNA5 induces programmed cell death when expressed in the yeast Saccharomyces cerevisiae.
Article in Frontiers in oncology, 2012. 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, 45 citations in OpenAlex.
- Gasdermins: multifunctional effectors of membrane permeabilization across cellular compartments.The FEBS journal · 2025Review
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Pyroptosis: molecular mechanisms and roles in disease.Cell research · 2025Review
- Review
- Gasdermins gone wild: new roles for GSDMs in regulating cellular homeostasis.Trends in cell biology · 2023Review
- Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells.Cell death and differentiation · 2023Article
- Neuronal glutathione loss leads to neurodegeneration involving gasdermin activation.Scientific reports · 2023Article
- Alternative splicing in shaping the molecular landscape of the cochlea.Frontiers in cell and developmental biology · 2023Review
- Precise Orchestration of Gasdermins' Pore-Forming Function by Posttranslational Modifications in Health and Disease.International journal of biological sciences · 2023Review
- How Pyroptosis Contributes to Inflammation and Fibroblast-Macrophage Cross-Talk in Rheumatoid Arthritis.Cells · 2022Review
- AudioGene: refining the natural history of KCNQ4, GSDME, WFS1, and COCH-associated hearing loss.Human genetics · 2022Article
- Gasdermin D: A potential mediator and prognostic marker of bladder cancer.Frontiers in molecular biosciences · 2022Article
- GSDME Increases Chemotherapeutic Drug Sensitivity by Inducing Pyroptosis in Retinoblastoma Cells.Oxidative medicine and cellular longevity · 2022Article
- Gasdermin E: A Prospective Target for Therapy of Diseases.Frontiers in pharmacology · 2022Review
- GSDMD-mediated pyroptosis: a critical mechanism of diabetic nephropathy.Expert reviews in molecular medicine · 2021Review
- The Versatile Gasdermin Family: Their Function and Roles in Diseases.Frontiers in immunology · 2021Review
- Gasdermin E-mediated programmed cell death: An unpaved path to tumor suppression.Journal of Cancer · 2021Review
- The gasdermins, a protein family executing cell death and inflammation.Nature reviews. Immunology · 2020Review
- Gasdermins in Apoptosis: New players in an Old Game.The Yale journal of biology and medicine · 2019Review
- The deafness gene GSDME: its involvement in cell apoptosis, secondary necrosis, and cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DFNA5 was first identified as a gene responsible for autosomal dominant deafness. Different mutations were found, but they all resulted in exon 8 skipping during splicing and premature termination of the protein. Later, it became clear that the protein also has a tumor suppression function and that it can induce apoptosis. Epigenetic silencing of the DFNA5 gene is associated with different types of cancers, including gastric and colorectal cancers as well as breast tumors. We introduced the wild-type and mutant DFNA5 allele in the yeast Saccharomyces cerevisiae. The expression of the wild-type protein was well tolerated by the yeast cells, although the protein was subject of degradation and often deposited in distinct foci when cells entered the diauxic shift. In contrast, cells had problems to cope with mutant DFNA5 and despite an apparent compensatory reduction in expression levels, the mutant protein still triggered a marked growth defect, which in part can be ascribed to its interaction with mitochondria. Consistently, cells with mutant DFNA5 displayed significantly increased levels of ROS and signs of programmed cell death. The latter occurred independently of the yeast caspase, Mca1, but involved the mitochondrial fission protein, Fis1, the voltage-dependent anion channel protein, Por1 and the mitochondrial adenine nucleotide translocators, Aac1 and Aac3. Recent data proposed DFNA5 toxicity to be associated to a globular domain encoded by exon 2-6. We confirmed these data by showing that expression of solely this domain confers a strong growth phenotype. In addition, we identified a point mutant in this domain that completely abrogated its cytotoxicity in yeast as well as human Human Embryonic Kidney 293T cells (HEK293T). Combined, our data underscore that the yeast system offers a valuable tool to further dissect the apoptotic properties of DFNA5.
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.