ArticleMolecular biology of the cell2007
Cdc6 stability is regulated by the Huwe1 ubiquitin ligase after DNA damage.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 137 citations in OpenAlex.
- Chemogenetic ubiquitin E1 inhibitor TAK-243 CRISPR screen uncovers HAPSTR1/HUWE1 axis in chromatin proteostasis and cell cycle control.Science advances · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- The E3 ubiquitin ligase HUWE1 is required for KRAS-induced lung cancer.Cell death & disease · 2026Article
- 3-hydroxyanthranilic acid suppresses colorectal cancer growth and enhances 5-fluorouracil sensitivity via the YY1-p53 and YY1-DKK4 axes.Frontiers in pharmacology · 2026Article
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.bioRxiv : the preprint server for biology · 2025Article
- The role of HECT-type E3 ubiquitin ligases in DNA damage response and repair.Cell death discovery · 2025Review
- HUWE1-Mediated Degradation of MUTYH Facilitates DNA Damage and Mitochondrial Dysfunction to Promote Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
- The E3 ligase HUWE1 increases the sensitivity of CRC to oxaliplatin through TOMM20 degradation.Oncogene · 2024Article
- Induced degradation of lineage-specific oncoproteins drives the therapeutic vulnerability of small cell lung cancer to PARP inhibitors.Science advances · 2024Article
- Suppression of interferon α and γ response by Huwe1-mediated Miz1 degradation promotes SARS-CoV-2 replication.Frontiers in immunology · 2024Article
- The ubiquitin-like modifier FAT10 covalently modifies HUWE1 and strengthens the interaction of AMBRA1 and HUWE1.PloS one · 2023Article
- Ubiquitin ligase E3 HUWE1/MULE targets transferrin receptor for degradation and suppresses ferroptosis in acute liver injury.Cell death and differentiation · 2022Article
- The giant E3 ligase HUWE1 is linked to tumorigenesis, spermatogenesis, intellectual disability, and inflammatory diseases.Frontiers in cellular and infection microbiology · 2022Review
- Huwe1 supports B-cell development, B-cell-dependent immunity, somatic hypermutation and class switch recombination by regulating proliferation.Frontiers in immunology · 2022Article
- HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain.Nature chemical biology · 2021Article
- Solenoid architecture of HUWE1 contributes to ligase activity and substrate recognition.Molecular cell · 2021Article
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27 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The Cdc6 protein is an essential component of pre-replication complexes (preRCs), which assemble at origins of DNA replication during the G1 phase of the cell cycle. Previous studies have demonstrated that, in response to ionizing radiation, Cdc6 is ubiquitinated by the anaphase promoting complex (APC(Cdh1)) in a p53-dependent manner. We find, however, that DNA damage caused by UV irradiation or DNA alkylation by methyl methane sulfonate (MMS) induces Cdc6 degradation independently of p53. We further demonstrate that Cdc6 degradation after these forms of DNA damage is also independent of cell cycle phase, Cdc6 phosphorylation of the known Cdk target residues, or the Cul4/DDB1 and APC(Cdh1) ubiquitin E3 ligases. Instead Cdc6 directly binds a HECT-family ubiquitin E3 ligase, Huwe1 (also known as Mule, UreB1, ARF-BP1, Lasu1, and HectH9), and Huwe1 polyubiquitinates Cdc6 in vitro. Degradation of Cdc6 in UV-irradiated cells or in cells treated with MMS requires Huwe1 and is associated with release of Cdc6 from chromatin. Furthermore, yeast cells lacking the Huwe1 ortholog, Tom1, have a similar defect in Cdc6 degradation. Together, these findings demonstrate an important and conserved role for Huwe1 in regulating Cdc6 abundance after DNA damage.
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