ArticleMolecular cell2020
CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer.Gynecologic oncology · 2022Trial
- TTC33 forms a complex with WDR61 and PHF5A to recruit factors relevant to genomic integrity.Nature communications · 2026Article
- Molecular modulators of cyclin-dependent kinase 4/6 inhibitor response in experimental glioma identified through genome-wide CRISPR-Cas9 screening.Neuro-oncology · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- FAM122A inhibition of PP2A-B55 through a bipartite binding mechanism.bioRxiv : the preprint server for biology · 2026Article
- A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture.bioRxiv : the preprint server for biology · 2026Article
- CHAMP1 complex promotes heterochromatin assembly and reduces replication stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Combining cryo-electron microscopy (cryo-EM) with orthogonal solution state methods to define the molecular basis of the phosphoprotein phosphatase family regulation and substrate specificity.Current opinion in structural biology · 2025Review
- Article
- CHAMP1 complex directs heterochromatin assembly and promotes homology-directed DNA repair.Nature communications · 2025Article
- Human axillary lymph node T follicular helper (Tfh) and Precursor-Tfh cells exhibit functional flexibility following seasonal influenza vaccination.Clinical & translational immunology · 2025Article
- Succinate dehydrogenase deficiency-driven succinate accumulation induces drug resistance in acute myeloid leukemia via ubiquitin-cullin regulation.Nature communications · 2024Article
- Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors.Molecular cancer · 2024Article
- Article
- FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs.Nature communications · 2024Article
- Increases in cyclin A/Cdk activity and in PP2A-B55 inhibition by FAM122A are key mitosis-inducing events.The EMBO journal · 2024Article
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- Article
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12 authors.
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Abstract
While effective anti-cancer drugs targeting the CHK1 kinase are advancing in the clinic, drug resistance is rapidly emerging. Here, we demonstrate that CRISPR-mediated knockout of the little-known gene FAM122A/PABIR1 confers cellular resistance to CHK1 inhibitors (CHK1is) and cross-resistance to ATR inhibitors. Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase that dephosphorylates the WEE1 protein and rescues WEE1 from ubiquitin-mediated degradation. The resulting increase in WEE1 protein expression reduces replication stress, activates the G2/M checkpoint, and confers cellular resistance to CHK1is. Interestingly, in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression. A combination of a CHK1i plus a WEE1 inhibitor can overcome CHK1i resistance of these tumor cells, thereby enhancing anti-cancer activity. The FAM122A expression level in a tumor cell can serve as a useful biomarker for predicting CHK1i sensitivity or resistance.
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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.