ArticleOncogene2022
The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 48 citations in OpenAlex.
- FUS-stabilized USP7 facilitates the bevacizumab resistance of ovarian cancer through deubiquitinating PTK2.Journal of gynecologic oncology · 2026Article
- Article
- A reliable prognostic model for hepatocellular carcinoma using neutrophil extracellular traps and immune related genes.Scientific reports · 2025Article
- Dihydromyricetin mitigates abdominal aortic aneurysmActa pharmaceutica Sinica. B · 2025Article
- Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
- Sodium formate induces development-dependent intestinal epithelial injury via necroptosis and apoptosis.Redox report : communications in free radical research · 2024Article
- Inhibition of USP7 enhances CD8Acta pharmacologica Sinica · 2024Article
- Effects of Chinese Gallotannins on Antioxidant Function, Intestinal Health, and Gut Flora in Broilers Challenged withAnimals : an open access journal from MDPI · 2024Article
- The deubiquitinase USP7 and E3 ligase TRIM21 regulate vasculogenic mimicry and malignant progression of RMS by balancing SNAI2 homeostasis.Journal of experimental & clinical cancer research : CR · 2024Article
- Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Protective effect of dexmedetomidine against delayed bone healing caused by morphine via PI3K/Akt mediated Nrf2 antioxidant defense system.Frontiers in pharmacology · 2024Article
- Exon-intron split analysis reveals posttranscriptional regulatory signals induced by high and low n-6/n-3 polyunsaturated fatty acid ratio diets in piglets.Journal of animal science · 2023Article
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heme oxygenase-1 (HO-1) is an inducible heme degradation enzyme that plays a cytoprotective role against various oxidative and inflammatory stresses. However, it has also been shown to exert an important role in cancer progression through a variety of mechanisms. Although transcription factors such as Nrf2 are involved in HO-1 regulation, the posttranslational modifications of HO-1 after oxidative insults and the underlying mechanisms remain unexplored. Here, we screened and identified that the deubiquitinase USP7 plays a key role in the control of redox homeostasis through promoting HO-1 deubiquitination and stabilization in hepatocytes. We used low-dose arsenic as a stress model which does not affect the transcriptional level of HO-1, and found that the interaction between USP7 and HO-1 is increased after arsenic exposure, leading to enhanced HO-1 expression and attenuated oxidative damages. Furthermore, HO-1 protein is ubiquitinated at K243 and subjected to degradation under resting conditions; whereas when after arsenic exposure, USP7 itself can be ubiquitinated at K476, thereafter promoting the binding between USP7 and HO-1, finally leading to enhanced HO-1 deubiquitination and protein accumulation. Moreover, depletion of USP7 and HO-1 inhibit liver tumor growth in vivo, and USP7 positively correlates with HO-1 protein level in clinical human hepatocellular carcinoma (HCC) specimens. In summary, our findings reveal a critical role of USP7 as a HO-1 deubiquitinating enzyme in the regulation of oxidative stresses, and suggest that USP7 inhibitor might be a potential therapeutic agent for treating HO-1 overexpressed liver cancers.
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