ArticleScience signaling2014
The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
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- Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex.Nature structural & molecular biology · 2024Article
- Shared genetic architecture of psychiatric disorders and hemorrhoidal disease: a large-scale genome-wide cross-trait analysis.Frontiers in psychiatry · 2024Article
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- Mitochondrial E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins.Cell death and differentiation · 2023Article
- Regulators mount up: the metabolic roles of apoptotic proteins.Frontiers in cell death · 2023Article
- Comprehensive analysis of the expression and prognosis for RBR E3 ubiquitin ligases in lung adenocarcinoma.Thoracic cancer · 2022Article
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- USP53 plays an antitumor role in hepatocellular carcinoma through deubiquitination of cytochrome c.Oncogenesis · 2022Article
- Cullin-9/p53 mediates HNRNPC degradation to inhibit erastin-induced ferroptosis and is blocked by MDM2 inhibition in colorectal cancer.Oncogene · 2022Article
- Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations.International journal of molecular sciences · 2022Article
- Inflammation and fibrosis in the coal dust-exposed lung described by confocal Raman spectroscopy.PeerJ · 2022Article
- Identification of quantitative trait loci for survival in the mutant dynactin p150Glued mouse model of motor neuron disease.PloS one · 2022Article
- Upregulation of apoptotic protease activating factor-1 expression correlates with anti-tumor effect of taxane drug.Medical oncology (Northwood, London, England) · 2021Article
- Long-Term Exposure to Nanosized TiOInternational journal of molecular sciences · 2021Article
- Membrane Depolarization Inhibits BIMMolecular neurobiology · 2021Article
- Treating MCF7 breast cancer cell with proteasome inhibitor Bortezomib restores apoptotic factors and sensitizes cell to Docetaxel.Medical oncology (Northwood, London, England) · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The ability to withstand mitochondrial damage is especially critical for the survival of postmitotic cells, such as neurons. Likewise, cancer cells can also survive mitochondrial stress. We found that cytochrome c (Cyt c), which induces apoptosis upon its release from damaged mitochondria, is targeted for proteasome-mediated degradation in mouse neurons, cardiomyocytes, and myotubes and in human glioma and neuroblastoma cells, but not in proliferating human fibroblasts. In mouse neurons, apoptotic protease-activating factor 1 (Apaf-1) prevented the proteasome-dependent degradation of Cyt c in response to induced mitochondrial stress. An RNA interference screen in U-87 MG glioma cells identified p53-associated Parkin-like cytoplasmic protein (PARC, also known as CUL9) as an E3 ligase that targets Cyt c for degradation. The abundance of PARC positively correlated with differentiation in mouse neurons, and overexpression of PARC reduced the abundance of mitochondrially-released cytosolic Cyt c in various cancer cell lines and in mouse embryonic fibroblasts. Conversely, neurons from Parc-deficient mice had increased sensitivity to mitochondrial damage, and neuroblastoma or glioma cells in which PARC or ubiquitin was knocked down had increased abundance of mitochondrially-released cytosolic Cyt c and decreased viability in response to stress. These findings suggest that PARC-mediated ubiquitination and degradation of Cyt c is a strategy engaged by both neurons and cancer cells to prevent apoptosis during conditions of mitochondrial stress.
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