ArticleMolecular and cellular biology2012
RAD6 regulates the dosage of p53 by a combination of transcriptional and posttranscriptional mechanisms.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses.Molecular medicine reports · 2026Article
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- Role of circRNA in E3 Modification under Human Disease.Biomolecules · 2022Review
- The circular RNA hsa_circ_0001394 promotes hepatocellular carcinoma progression by targeting the miR-527/UBE2A axis.Cell death discovery · 2022Article
- Epigenetic regulation of the Warburg effect by H2B monoubiquitination.Cell death and differentiation · 2020Article
- Identification of cancer sex-disparity in the functional integrity of p53 and its X chromosome network.Nature communications · 2019Article
- RAD6B Plays a Critical Role in Neuronal DNA Damage Response to Resist Neurodegeneration.Frontiers in cellular neuroscience · 2019Article
- High expression of ubiquitin-conjugating enzyme E2A predicts poor prognosis in hepatocellular carcinoma.Oncology letters · 2018Article
- Interactome Analysis Reveals a Novel Role for RAD6 in the Regulation of Proteasome Activity and Localization in Response to DNA Damage.Molecular and cellular biology · 2017Article
- Neuronal hemoglobin affects dopaminergic cells' response to stress.Cell death & disease · 2017Article
- Damage-inducible intragenic demethylation of the human TP53 tumor suppressor gene is associated with transcription from an alternative intronic promoter.Molecular carcinogenesis · 2016Article
- UBE2B is implicated in myofibrillar protein loss in catabolic C2C12 myotubes.Journal of cachexia, sarcopenia and muscle · 2016Article
- A conserved RAD6-MDM2 ubiquitin ligase machinery targets histone chaperone ASF1A in tumorigenesis.Oncotarget · 2015Article
- Role of E2-Ub-conjugating enzymes during skeletal muscle atrophy.Frontiers in physiology · 2015Review
- RAD6 promotes homologous recombination repair by activating the autophagy-mediated degradation of heterochromatin protein HP1.Molecular and cellular biology · 2015Article
- MDM2's social network.Oncogene · 2014Review
- The PTTG1-binding factor (PBF/PTTG1IP) regulates p53 activity in thyroid cells.Endocrinology · 2014Article
- Human RAD6 promotes G1-S transition and cell proliferation through upregulation of cyclin D1 expression.PloS one · 2014Article
- Ubiquitin- and ubiquitin-like proteins-conjugating enzymes (E2s) in breast cancer.Molecular biology reports · 2013Article
- Histone H2B lysine 120 monoubiquitination is required for embryonic stem cell differentiation.Cell research · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maintaining an appropriate cellular concentration of p53 is critical for cell survival and normal development in various organisms. In this study, we provide evidence that the human E2 ubiquitin-conjugating enzyme RAD6 plays a critical role in regulating p53 protein levels under both normal and stress conditions. Knockdown and overexpression of RAD6 affected p53 turnover and transcription. We showed that RAD6 can form a ternary complex with MDM2 and p53 that contributes to the degradation of p53. Chromatin immunoprecipitation (ChIP) analysis showed that RAD6 also binds to the promoter and coding regions of the p53 gene and modulates the levels of H3K4 and K79 methylation on local chromatin. When the cells were exposed to stress stimuli, the RAD6-MDM2-p53 ternary complex was disrupted; RAD6 was then recruited to the chromatin of the p53 gene, resulting in an increase in histone methylation and p53 transcription. Further studies showed that stress-induced p53 transcriptional activation, cell apoptosis, and disrupted cell cycle progression are all RAD6 dependent. Overall, this work demonstrates that RAD6 regulates p53 levels in a "yin-yang" manner through a combination of two distinct mechanisms in mammalian cells.
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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.