ArticleThe Journal of biological chemistry2014
The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53 by regulating its oligomerization.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research.International journal of molecular sciences · 2021Pooled it
- NUAK1 Inhibition Alleviates Ischemia-Reperfusion Injury via SYNE1-YAP1.Circulation research · 2026Article
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- HERC2 as a Potential Biomarker for Prognosis and Response to Bevacizumab in Ovarian Cancer: A Bioinformatics Approach.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Germline Whole-Exome Sequencing in Non-Smoker Lung Cancer Patients Reveals Pathogenic Variants in Lung Cancer Driver Genes.Genes, chromosomes & cancer · 2025Article
- The disordered negatively charged C-terminus of the large HECT E3 ubiquitin ligase HERC2 provides structural and thermal stability to the HECT C-lobe.Protein science : a publication of the Protein Society · 2024Article
- Autophagy dysregulation via the USP20-ULK1 axis in the HERC2-related neurodevelopmental disorder.Cell death discovery · 2024Article
- DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.Advances in experimental medicine and biology · 2024Review
- Validation of a murine proteome-wide phage display library for identification of autoantibody specificities.JCI insight · 2023Article
- Istradefylline modulates purinergic enzymes and reduces malignancy-associated factors in B16F10 melanoma cells.Purinergic signalling · 2023Article
- Malignancies in Prader-Willi Syndrome: Results From a Large International Cohort and Literature Review.The Journal of clinical endocrinology and metabolism · 2023Review
- Ubiquitin E3 ligases in cancer: somatic mutation and amplification.BMB reports · 2023Review
- The genomic landscape of familial glioma.Science advances · 2023Article
- Pan-cancer association of DNA repair deficiencies with whole-genome mutational patterns.eLife · 2023Article
- The Role of HECT E3 Ubiquitin Ligases in Colorectal Cancer.Biomedicines · 2023Review
- HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.Cellular and molecular life sciences : CMLS · 2022Article
- Involvement of HECT-type E3 ubiquitin ligase genes in salt chemotaxis learning in Caenorhabditis elegans.Genetics · 2022Article
- The Downregulation of Both Giant HERCs,Journal of clinical medicine · 2022Article
- Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition.Journal of translational medicine · 2021Article
- Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor suppressor p53 is a transcription factor that coordinates the cellular response to several kinds of stress. p53 inactivation is an important step in tumor progression. Oligomerization of p53 is critical for its posttranslational modification and its ability to regulate the transcription of target genes necessary to inhibit tumor growth. Here we report that the HECT E3 ubiquitin ligase HERC2 interacts with p53. This interaction involves the CPH domain of HERC2 (a conserved domain within Cul7, PARC, and HERC2 proteins) and the last 43 amino acid residues of p53. Through this interaction, HERC2 regulates p53 activity. RNA interference experiments showed how HERC2 depletion reduces the transcriptional activity of p53 without affecting its stability. This regulation of p53 activity by HERC2 is independent of proteasome or MDM2 activity. Under these conditions, up-regulation of cell growth and increased focus formation were observed, showing the functional relevance of the HERC2-p53 interaction. This interaction was maintained after DNA damage caused by the chemotherapeutic drug bleomycin. In these stressed cells, p53 phosphorylation was not impaired by HERC2 knockdown. Interestingly, p53 mutations that affect its tetramerization domain disrupted the HERC2-p53 interaction, suggesting a role for HERC2 in p53 oligomerization. This regulatory role was shown using cross-linking assays. Thus, the inhibition of p53 activity after HERC2 depletion can be attributed to a reduction in p53 oligomerization. Ectopic expression of HERC2 (residues 2292-2923) confirmed these observations. Together, these results identify HERC2 as a novel regulator of p53 signaling.
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