ArticleScience advances2020
CHK2-FOXK axis promotes transcriptional control of autophagy programs.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 64 citations in OpenAlex.
- AKT Phosphorylation of FOXK2 at Ser398 Impacts Breast Cancer Cell Growth and Viability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- PRMT7-mediated arginine methylation of FOXK activates Wnt/β-catenin signalling to drive doxorubicin resistance in diffuse large B-cell lymphoma.Clinical and translational medicine · 2026Article
- XunZi, an AI biologist, reveals disease-modifying targets.Nature biomedical engineering · 2026Article
- pCancer and FOXK2 (Forkhead Box K2): Oncogenic and Tumor-Suppressive Roles of FOXK2 in Cancer.Biochemical genetics · 2026Review
- FOXK2/SH2D3A axis recruits EGFR to drive papillary thyroid cancer progression and confers sensitivity to EGFR inhibition.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Review
- FOXK1: a multifaceted regulator in metabolic reprogramming and disease progression.Biology direct · 2026Review
- Deficiency ofZoological research · 2026Article
- CDCA7 promotes chemoresistance of drug-tolerant persister cells in breast cancer by upregulating the expression of autophagy-related protein genes.Frontiers in immunology · 2026Article
- CHK1 and CHK2 as Context-Dependent Rheostats of Genotoxic Stress: Implications for Cell Fate and Tumor Immunity.International journal of biological sciences · 2026Review
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- A ROS-mediated oxidation-O-GlcNAcylation cascade governs ferroptosis.Nature cell biology · 2025Article
- Interplay of Oxidative Stress, Autophagy, and Rubicon in Ovarian Follicle Dynamics: Orchestrating Ovarian Aging.Antioxidants (Basel, Switzerland) · 2025Review
- Rubicon, a Key Molecule for Oxidative Stress-Mediated DNA Damage, in Ovarian Granulosa Cells.Antioxidants (Basel, Switzerland) · 2025Article
- The role of FOXK2-FBXO32 in breast cancer tumorigenesis: Insights into ribosome-associated pathways.Thoracic cancer · 2025Article
- Guarding against digestive-system cancers: Unveiling the role of Chk2 as a potential therapeutic target.Genes & diseases · 2025Review
- The essential role of TTC28 in maintaining chromosomal stability via HSPA8 chaperone-mediated autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MicroRNA-mediated autophagy and drug resistance in cancer: mechanisms and therapeutic strategies.Discover oncology · 2024Review
- Premature senescence is regulated by crosstalk among TFEB, the autophagy lysosomal pathway and ROS derived from damaged mitochondria in NaAsOCell death discovery · 2024Article
- NLRP4 renders pancreatic cancer resistant to olaparib through promotion of the DNA damage response and ROS-induced autophagy.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is an evolutionarily conserved catabolic process, which plays a vital role in removing misfolded proteins and clearing damaged organelles to maintain internal environment homeostasis. Here, we uncovered the checkpoint kinase 2 (CHK2)-FOXK (FOXK1 and FOXK2) axis playing an important role in DNA damage-mediated autophagy at the transcriptional regulation layer. Mechanistically, following DNA damage, CHK2 phosphorylates FOXK and creates a 14-3-3γ binding site, which, in turn, traps FOXK proteins in the cytoplasm. Because FOXK functions as the transcription suppressor of ATGs, DNA damage-mediated FOXKs' cytoplasmic trapping induces autophagy. In addition, we found that a cancer-derived FOXK mutation induces FOXK hyperphosphorylation and enhances autophagy, resulting in chemoresistance. Cotreatment with cisplatin and chloroquine overcomes the chemoresistance caused by FOXK mutation. Overall, our study highlights a mechanism whereby DNA damage triggers autophagy by increasing autophagy genes via CHK2-FOXK-mediated transcriptional control, and misregulation of this pathway contributes to chemoresistance.
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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.