ArticleOncogene2010
MdmX is a substrate for the deubiquitinating enzyme USP2a.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 96 citations in OpenAlex.
- Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer.Cell death & disease · 2026Article
- Deubiquitinases and Cancer.Journal of pharmacy & bioallied sciences · 2024Review
- Roles of deubiquitinases in urologic cancers (Review).Oncology letters · 2024Review
- Roles of naïve CD4Journal of translational medicine · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Inhibition of USP2 Enhances TRAIL-Mediated Cancer Cell Death through Downregulation of Survivin.International journal of molecular sciences · 2023Article
- Targeted therapy based on ubiquitin-specific proteases, signalling pathways and E3 ligases in non-small-cell lung cancer.Frontiers in oncology · 2023Review
- DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities.Experimental & molecular medicine · 2022Review
- The emerging role of deubiquitylating enzymes as therapeutic targets in cancer metabolism.Cancer cell international · 2022Review
- USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes.International journal of molecular sciences · 2021Review
- The Cross Talk Between p53 and mTOR Pathways in Response to Physiological and Genotoxic Stresses.Frontiers in cell and developmental biology · 2021Review
- Decreased USP2a Expression Inhibits Trophoblast Invasion and Associates With Recurrent Miscarriage.Frontiers in immunology · 2021Article
- Dissenting degradation: Deubiquitinases in cell cycle and cancer.Seminars in cancer biology · 2020Review
- Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics.Cancers · 2020Review
- Downregulation of ubiquitin-specific protease 2 possesses prognostic and diagnostic value and promotes the clear cell renal cell carcinoma progression.Annals of translational medicine · 2020Article
- The role of ubiquitin-specific peptidases in cancer progression.Journal of biomedical science · 2019Review
- Metabolic stress controls mutant p53 R248Q stability in acute myeloid leukemia cells.Scientific reports · 2019Article
- TGF-β signaling pathway mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
It has previously been shown that ubiquitin-specific protease 2a (USP2a) is a regulator of the Mdm2/p53 pathway. USP2a binds to Mdm2 and can deubiquitinate Mdm2 without reversing Mdm2-mediated p53 ubiquitination. Overexpression of USP2a causes accumulation of Mdm2 and promotes p53 degradation. We now show that MdmX is also a substrate for USP2a. MdmX associates with USP2a independently of Mdm2. Ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2-mediated degradation of MdmX. This correlates with the ability of wild-type USP2a to deubiquitinate MdmX. siRNA-mediated knockdown of USP2a in NTERA-2 testicular embryonal carcinoma cells and MCF7 breast cancer cells causes destabilization of MdmX and results in a decrease in MdmX protein levels, showing that endogenous USP2a participates in the regulation of MdmX stability. The therapeutic drug, cisplatin decreases MdmX protein expression. USP2a mRNA and protein levels were also reduced after cisplatin exposure. The magnitude and time course of USP2a downregulation suggests that the reduction in USP2a levels could contribute to the decrease in MdmX expression following treatment with cisplatin. Knockdown of USP2a increases the sensitivity of NTERA-2 cells to cisplatin, raising the possibility that suppression of USP2a in combination with cisplatin may be an approach for cancer therapy.
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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.