ArticleThe FEBS journal2020
Direct regulation of Chk1 protein stability by E3 ubiquitin ligase HUWE1.
Article in The FEBS journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.PLoS genetics · 2026Article
- Proteasomal-dependent CHK1 degradation leads to DNA damage accumulation in ALS cellular model systems.Cell death & disease · 2026Article
- A C-degron regulates Chk1 kinase by allowing stability of inactive Chk1 and by making it short- lived upon activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity.Nature communications · 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
- CHK1 inhibition increases the therapeutic response to radiotherapy via antitumor immunity in ARID1A-deficient colorectal cancer.Cell death & disease · 2025Article
- Proteomics-Based Trapping to Study Substrates of Histone Deacetylase 6 Catalytic Domain 1.Biochemistry · 2025Article
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model.International journal of molecular sciences · 2025Article
- Protein ubiquitination in ovarian cancer immunotherapy: The progress and therapeutic strategy.Genes & diseases · 2024Review
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.The Biochemical journal · 2024Review
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 2024Review
- Ki-67 is necessary during DNA replication for fork protection and genome stability.Genome biology · 2024Article
- The E3 ligase HUWE1 increases the sensitivity of CRC to oxaliplatin through TOMM20 degradation.Oncogene · 2024Article
- Article
- HAPSTR1 localizes HUWE1 to the nucleus to limit stress signaling pathways.Cell reports · 2023Article
- HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation.eLife · 2023Article
- Protein degradation: expanding the toolbox to restrain cancer drug resistance.Journal of hematology & oncology · 2023Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The HECT E3 ubiquitin ligase HUWE1 is required for a wide array of important functions in cell biology. Although HUWE1 is known to play a role in DNA damage signaling, the mechanism(s) that underlie this function remain elusive. HUWE1 regulates effectors of DNA replication and genotoxic stress tolerance. However, the loss of HUWE1 can also result in the accrual of significant endogenous DNA damage due to insufficient remediation of replication stress induced by an overabundance of key substrates. We discovered that HUWE1 depletion leads to a significant increase in levels of the single-strand break effector kinase Chk1, independent of the DNA damage response, activation of apical DNA damage repair (DDR) signaling kinases (ATM and ATR), and the tumor suppressor p53. We also identified multiple lysine residues on Chk1 that are polyubiquitinated by HUWE1 in vitro, many of which are within the kinase domain. HUWE1 knockdown also markedly prolonged the protein half-life of Chk1 in steady-state conditions and resulted in greater stabilization of Chk1 protein than depletion of Cul4A, an E3 ubiquitin ligase previously described to control Chk1 abundance. Moreover, prolonged replication stress induced by hydroxyurea or camptothecin resulted in a reduction of Chk1 protein levels, which was rescued by HUWE1 knockdown. Our study indicates that HUWE1 plays a significant role in the regulation of the DDR signaling pathway by directly modulating the abundance of Chk1 protein.
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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.