ArticleOncogene2017
DUB3 and USP7 de-ubiquitinating enzymes control replication inhibitor Geminin: molecular characterization and associations with breast cancer.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 62 citations in OpenAlex.
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- Review
- Article
- Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.Molecular cancer · 2024Article
- USP7 Deregulation Impairs S Phase Specific DNA Repair after Irradiation in Breast Cancer Cells.Biomedicines · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Implications of ubiquitination and the maintenance of replication fork stability in cancer therapy.Bioscience reports · 2023Review
- m6A eraser FTO impairs gemcitabine resistance in pancreatic cancer through influencing NEDD4 mRNA stability by regulating the PTEN/PI3K/AKT pathway.Journal of experimental & clinical cancer research : CR · 2023Article
- Article
- COMMD3 loss drives invasive breast cancer growth by modulating copper homeostasis.Journal of experimental & clinical cancer research : CR · 2023Article
- Emerging potential of ubiquitin-specific proteases and ubiquitin-specific proteases inhibitors in breast cancer treatment.World journal of clinical cases · 2022Review
- Hao-Fountain syndrome and genital disorders: report of a new possible association.Italian journal of pediatrics · 2022Article
- Article
- DUB3/KLF4 combats tumor growth and chemoresistance in hepatocellular carcinoma.Cell death discovery · 2022Article
- RNA interference screens discover proteases as synthetic lethal partners of PI3K inhibition in breast cancer cells.Theranostics · 2022Article
- Highlights in USP7 inhibitors for cancer treatment.Frontiers in chemistry · 2022Review
- The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review.Cancer cell international · 2021Review
- Coordinating DNA Replication and Mitosis through Ubiquitin/SUMO and CDK1.International journal of molecular sciences · 2021Review
- USP7 limits CDK1 activity throughout the cell cycle.The EMBO journal · 2021Article
- Ubiquitin-specific protease 7 as a potential therapeutic target in dogs with hematopoietic malignancies.Journal of veterinary internal medicine · 2021Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Correct control of DNA replication is crucial to maintain genomic stability in dividing cells. Inappropriate re-licensing of replicated origins is associated with chromosomal instability (CIN), a hallmark of cancer progression that at the same time provides potential opportunities for therapeutic intervention. Geminin is a critical inhibitor of the DNA replication licensing factor Cdt1. To properly achieve its functions, Geminin levels are tightly regulated through the cell cycle by ubiquitin-dependent proteasomal degradation, but the de-ubiquitinating enzymes (DUBs) involved had not been identified. Here we report that DUB3 and USP7 control human Geminin. Overexpression of either DUB3 or USP7 increases Geminin levels through reduced ubiquitination. Conversely, depletion of DUB3 or USP7 reduces Geminin levels, and DUB3 knockdown increases re-replication events, analogous to the effect of Geminin depletion. In exploring potential clinical implications, we found that USP7 and Geminin are strongly correlated in a cohort of invasive breast cancers (P<1.01E-08). As expected, Geminin expression is highly prognostic. Interestingly, we found a non-monotonic relationship between USP7 and breast cancer-specific survival, with both very low or high levels of USP7 associated with poor outcome, independent of estrogen receptor status. Altogether, our data identify DUB3 and USP7 as factors that regulate DNA replication by controlling Geminin protein stability, and suggest that USP7 may be involved in Geminin dysregulation during breast cancer progression.
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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.