ArticleOncogene2008
Retinoblastoma protein modulates gankyrin-MDM2 in regulation of p53 stability and chemosensitivity in cancer cells.
Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Synthesis and evaluation of 2,5-substituted pyrimidines as small-molecule gankyrin binders.Future medicinal chemistry · 2024Article
- Gankyrin inhibits ferroptosis through the p53/SLC7A11/GPX4 axis in triple-negative breast cancer cells.Scientific reports · 2023Article
- MDM2 is a Potential Target Gene of Glycyrrhizic Acid for Circumventing Breast Cancer Resistance to Tamoxifen: Integrative Bioinformatics Analysis.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Gankyrin as Potential Biomarker for Colorectal Cancer With Occult Liver Metastases.Frontiers in oncology · 2021Article
- Article
- Gankyrin as a potential therapeutic target for cancer.Investigational new drugs · 2017Review
- Testis specific Y-like 5: gene expression, methylation and implications for drug sensitivity in prostate carcinoma.BMC cancer · 2017Article
- Inhibition of apoptosis by oncogenic hepatitis B virus X protein: Implications for the treatment of hepatocellular carcinoma.World journal of hepatology · 2016Review
- Scratching the Surface: Resurfacing Proteins to Endow New Properties and Function.Cell chemical biology · 2016Review
- Article
- Discovery of a small-molecule binder of the oncoprotein gankyrin that modulates gankyrin activity in the cell.Scientific reports · 2016Article
- Gankyrin is a predictive and oncogenic factor in well-differentiated and dedifferentiated liposarcoma.Oncotarget · 2014Article
- A miR-199a/miR-214 self-regulatory network via PSMD10, TP53 and DNMT1 in testicular germ cell tumor.Scientific reports · 2014Article
- The Complex Relationship between Liver Cancer and the Cell Cycle: A Story of Multiple Regulations.Cancers · 2014Article
- Tumour suppressor genes in chemotherapeutic drug response.Bioscience reports · 2012Review
- Gankyrin Oncoprotein: Structure, Function, and Involvement in Cancer.Current chemical biology · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
MDM2 is a key ubiquitin E3 ligase for p53 and its activity is critically regulated by a set of modulators, including ARF, p300, YY1 and recently by gankyrin, an oncoprotein frequently overexpressed in human heptocellular carcinomas. We have previously shown that MDM2 binds to and promotes retinoblastoma protein (Rb) degradation. Here we show that Rb inhibits MDM2 E3 ligase activity resulting in stabilization of p53. In addition, we demonstrated that Rb inhibits MDM2-mediated p53 ubiquitination in a gankyrin-dependent manner and the Rb-gankyrin interaction is critical for Rb-induced p53 stabilization. Furthermore, acute ablation of Rb facilitates gankyrin-mediated p53 destabilization, and desensitizes cancer cells for chemotherapy-induced apoptosis. These results indicate that Rb antagonizes gankyrin to inhibit MDM2-mediate p53 ubiquitination in cancer cells and suggest that the status of both p53 and Rb is important for efficacy of cancer chemotherapy.
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Registered trials
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