ArticleCell death & disease2013
CHIP has a protective role against oxidative stress-induced cell death through specific regulation of endonuclease G.
Article in Cell death & disease, 2013. 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, 34 citations in OpenAlex.
- Impact of severe hypoglycemia on the heat shock and related protein response.Scientific reports · 2021Trial
- Glucose-induced STUB1-GOT2 axis promotes aspartate synthesis and mitochondrial dysfunction in bladder cancer.Cell death & disease · 2025Article
- The ubiquitin-proteasome system in circadian regulation.Frontiers in neuroscience · 2025Review
- CHIP protects against septic acute kidney injury by inhibiting NLRP3-mediated pyroptosis.iScience · 2023Article
- Mitochondrial Factors in the Cell Nucleus.International journal of molecular sciences · 2023Review
- Comparison of the effects of oxidative and inflammatory stresses on rat chondrocyte senescence.Scientific reports · 2023Article
- Nuclear endonuclease G controls cell proliferation in ovarian cancer.FEBS open bio · 2023Article
- Article
- Many Functions of Telomerase Components: Certainties, Doubts, and Inconsistencies.International journal of molecular sciences · 2022Review
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Serum from Older Adults Increases Apoptosis and Molecular Aging Markers in Human Hippocampal Progenitor Cells.Aging and disease · 2021Article
- Alternative Splicing of Human Telomerase Reverse Transcriptase (hTERT) and Its Implications in Physiological and Pathological Processes.Biomedicines · 2021Review
- C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside.Current neuropharmacology · 2021Review
- Management of Hypercholesterolemia Through Dietary ß-glucans-Insights From a Zebrafish Model.Frontiers in nutrition · 2021Article
- The E3 ubiquitin ligase STUB1 attenuates cell senescence by promoting the ubiquitination and degradation of the core circadian regulator BMAL1.The Journal of biological chemistry · 2020Article
- Mechanisms of protein toxicity in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2018Review
- Review
- Differential HspBP1 expression accounts for the greater vulnerability of neurons than astrocytes to misfolded proteins.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial DNA fragmentation and regulates macrophage cell death after trauma.Cell death & disease · 2017Article
- Stability of the cancer target DDIAS is regulated by the CHIP/HSP70 pathway in lung cancer cells.Cell death & disease · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress is implicated in carcinogenesis, aging, and neurodegenerative diseases. The E3 ligase C terminus of Hsc-70 interacting protein (CHIP) has a protective role against various stresses by targeting damaged proteins for proteasomal degradation, and thus maintains protein quality control. However, the detailed mechanism by which CHIP protects cells from oxidative stress has not been demonstrated. Here, we show that depletion of CHIP led to elevated Endonuclease G (EndoG) levels and enhanced cell death upon oxidative stress. In contrast, CHIP overexpression reduced EndoG levels, and resulted in reduced or no oxidative stress-induced cell death in cancer cells and primary rat cortical neurons. Under normal conditions Hsp70 mediated the interaction between EndoG and CHIP, downregulating EndoG levels in a Hsp70/proteasome-dependent manner. However, under oxidative stress Hsp70 no longer interacted with EndoG, and the stabilized EndoG translocated to the nucleus and degraded chromosomal DNA. Our data suggest that regulation of the level of EndoG by CHIP in normal conditions may determine the sensitivity to cell death upon oxidative stress. Indeed, injection of H2O2 into the rat brain markedly increased cell death in aged mice compared with young mice, which correlated with elevated levels of EndoG and concurrent downregulation of CHIP in aged mice. Taken together, our findings demonstrate a novel protective mechanism of CHIP against oxidative stress through regulation of EndoG, and provide an opportunity to modulate oxidative stress-induced cell death in cancer and aging.
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.