ArticleMolecular oncology2020
Regulation of the MDM2-p53 pathway by the ubiquitin ligase HERC2.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 62 citations in OpenAlex.
- HERC2 as a Potential Biomarker for Prognosis and Response to Bevacizumab in Ovarian Cancer: A Bioinformatics Approach.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Extra-Ribosomal Roles for Ribosomal Proteins and Their Relevance to Tumour Suppression, Carcinogenesis and Cancer Progression.Cancers · 2025Review
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Correlation of p53 oligomeric status and its subcellular localization in the presence of the AML-associated NPM mutant.PloS one · 2025Article
- Long noncoding RNAs in ubiquitination, protein degradation, and human diseases.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Review
- Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment.EXCLI journal · 2024Review
- Ubiquitin E3 ligases in cancer: somatic mutation and amplification.BMB reports · 2023Review
- The genomic landscape of familial glioma.Science advances · 2023Article
- The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer.Biomedicines · 2023Review
- HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway.Journal of experimental & clinical cancer research : CR · 2023Article
- HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.Cellular and molecular life sciences : CMLS · 2022Article
- Targeting Apoptosis in AML: Where Do We Stand?Cancers · 2022Review
- MAGED2 Is Required under Hypoxia for cAMP Signaling by Inhibiting MDM2-Dependent Endocytosis of G-Alpha-S.Cells · 2022Article
- Potential anti-hepatocellular carcinoma properties and mechanisms of action of clerodane diterpenes isolated from Polyalthia longifolia seeds.Scientific reports · 2022Article
- Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2022Article
- HERC3 regulates epithelial-mesenchymal transition by directly ubiquitination degradation EIF5A2 and inhibits metastasis of colorectal cancer.Cell death & disease · 2022Article
- HERC3 directly targets RPL23A for ubiquitination degradation and further regulates Colorectal Cancer proliferation and the cell cycle.International journal of biological sciences · 2022Article
- Ribosomal L1 domain-containing protein 1 coordinates with HDM2 to negatively regulate p53 in human colorectal Cancer cells.Journal of experimental & clinical cancer research : CR · 2021Article
- PRDX2 promotes the proliferation of colorectal cancer cells by increasing the ubiquitinated degradation of p53.Cell death & disease · 2021Article
- miR-29a sensitizes the response of glioma cells to temozolomide by modulating the P53/MDM2 feedback loop.Cellular & molecular biology letters · 2021Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 tumor suppressor protein is a transcription factor that plays a prominent role in protecting cells from malignant transformation. Protein levels of p53 and its transcriptional activity are tightly regulated by the ubiquitin E3 ligase MDM2, the gene expression of which is transcriptionally regulated by p53 in a negative feedback loop. The p53 protein is transcriptionally active as a tetramer, and this oligomerization state is modulated by a complex formed by NEURL4 and the ubiquitin E3 ligase HERC2. Here, we report that MDM2 forms a complex with oligomeric p53, HERC2, and NEURL4. HERC2 knockdown results in a decline in MDM2 protein levels without affecting its protein stability, as it reduces its mRNA expression by inhibition of its promoter activation. DNA damage induced by bleomycin dissociates MDM2 from the p53/HERC2/NEURL4 complex and increases the phosphorylation and acetylation of oligomeric p53 bound to HERC2 and NEURL4. Moreover, the MDM2 promoter, which contains p53-response elements, competes with HERC2 for binding of oligomeric, phosphorylated and acetylated p53. We integrate these findings in a model showing the pivotal role of HERC2 in p53-MDM2 loop regulation. Altogether, these new insights in p53 pathway regulation are of great interest in cancer and may provide new therapeutic targets.
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