ArticleNature chemical biology2023
SIRT1 deacetylates WEE1 and sensitizes cancer cells to WEE1 inhibition.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- An update of predictive biomarkers related to WEE1 inhibition in cancer therapy.Journal of cancer research and clinical oncology · 2024Pooled it
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- Photodynamic therapy mediates antitumor effects through multiple non‑apoptotic cell death pathways.Journal of biomedical science · 2026Review
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- SLC6A19-mediated tryptophan uptake suppresses renal cell carcinoma metastasis via activating NADOncogenesis · 2025Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Fbxo2 inhibits cell proliferation, migration and invasion by the ubiquitin-mediated degradation of WEE1 in renal cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Macrophage WEE1 Directly Binds to and Phosphorylates NF-κB p65 Subunit to Induce Inflammatory Response and Drive Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Diabetes-associated sleep fragmentation impairs liver and heart functionActa pharmaceutica Sinica. B · 2025Article
- Article
- Genetic Code Expansion: Recent Developments and Emerging Applications.Chemical reviews · 2025Review
- Emerging roles of mitochondrial sirtuin SIRT5 in succinylation modification and cancer development.Frontiers in immunology · 2025Review
- Reversible Acetylation of Non-histone Proteins in Human Cancers.Results and problems in cell differentiation · 2025Review
- Induction of ferroptosis by SIRT1 knockdown alleviates cytarabine resistance in acute myeloid leukemia by activating the HMGB1/ACSL4 pathway.International journal of oncology · 2025Article
- Wee1 inhibitor PD0166285 sensitized TP53 mutant lung squamous cell carcinoma to cisplatin via STAT1.Cancer cell international · 2024Article
- USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling.Nature communications · 2024Article
- ATR limits Rad18-mediated PCNA monoubiquitination to preserve replication fork and telomerase-independent telomere stability.The EMBO journal · 2024Article
- Article
- From sequencing to validation: NGS-based exploration of plasma miRNA in papillary thyroid carcinoma.Frontiers in oncology · 2024Article
- Targeting sirtuins for cancer therapy: epigenetics modifications and beyond.Theranostics · 2024Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cell-cycle checkpoint kinase WEE1 is emerging as a therapeutic target for cancer treatment. However, how its catalytic activity is regulated remains poorly understood, and reliable biomarkers for predicting response to WEE1 inhibitor remain to be identified. Here we identify an evolutionarily conserved segment surrounding its Lys177 residue that inhibits WEE1 activity through an intermolecular interaction with the catalytic kinase domain. Upon DNA damage, CHK1-dependent phosphorylation of WEE1 at Ser642 primes GCN5-mediated acetylation at Lys177, resulting in dissociation of the inhibitory segment from the kinase domain and subsequent activation of WEE1 and cell-cycle checkpoints. Conversely, SIRT1 associates with and deacetylates WEE1, which maintains it in an inactive state. Consequently, SIRT1 deficiency induces WEE1 hyperacetylation and activation, rendering cancer cells resistant to WEE1 inhibition. These results suggest that SIRT1 expression level and abundance of WEE1 Lys177 acetylation in tumor cells can serve as useful biomarkers for predicting WEE1 inhibitor sensitivity or resistance.
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Registered trials
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.