ArticleCancer gene therapy2022
Epigenetically silenced apoptosis-associated tyrosine kinase (AATK) facilitates a decreased expression of Cyclin D1 and WEE1, phosphorylates TP53 and reduces cell proliferation in a kinase-dependent manner.
Article in Cancer gene therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- DNA Methylation as a Mediator of Cardiovascular Disease Risk in Relation to PTSD Severity: Identification of Potential Epigenetic Biomarkers.medRxiv : the preprint server for health sciences · 2026Article
- Bioinformatics differential expression analysis of the effect of cannabidiol in chronic myeloid leukaemia cell line.Global medical genetics · 2025Article
- Identification of Ageing-related Hub Genes in Humans, Mouse and Rat Based on Bioinformatics Analysis.Annals of neurosciences · 2025Article
- Epigenetic silencing and CRISPR-mediated reactivation of tight junction protein claudin10b (CLDN10B) in renal cancer.Clinical epigenetics · 2025Article
- Identification of N6-methyladenosine-associated ferroptosis biomarkers in cervical cancer.Hereditas · 2025Article
- Expression of miRNA-338-3p/miRNA-1250-5p/miRNA-3065-5p clusters in peripheral blood mononuclear cells of ischemic stroke.Scientific reports · 2025Article
- Article
- SIAH3 is frequently epigenetically silenced in cancer and regulates mitochondrial metabolism.International journal of cancer · 2025Article
- RFW captures species-level metagenomic functions by integrating genome annotation information.Cell reports methods · 2024Article
- Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.MedComm · 2023Review
- Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing.International journal of molecular sciences · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Silencing of the Apoptosis associated Tyrosine Kinase gene (AATK) has been described in cancer. In our study, we specifically investigated the epigenetic inactivation of AATK in pancreatic adenocarcinoma, lower grade glioma, lung, breast, head, and neck cancer. The resulting loss of AATK correlates with impaired patient survival. Inhibition of DNA methyltransferases (DNMTs) reactivated AATK in glioblastoma and pancreatic cancer. In contrast, epigenetic targeting via the CRISPR/dCas9 system with either EZH2 or DNMT3A inhibited the expression of AATK. Via large-scale kinomic profiling and kinase assays, we demonstrate that AATK acts a Ser/Thr kinase that phosphorylates TP53 at Ser366. Furthermore, whole transcriptome analyses and mass spectrometry associate AATK expression with the GO term 'regulation of cell proliferation'. The kinase activity of AATK in comparison to the kinase-dead mutant mediates a decreased expression of the key cell cycle regulators Cyclin D1 and WEE1. Moreover, growth suppression through AATK relies on its kinase activity. In conclusion, the Ser/Thr kinase AATK represses growth and phosphorylates TP53. Furthermore, expression of AATK was correlated with a better patient survival for different cancer entities. This data suggests that AATK acts as an epigenetically inactivated tumor suppressor gene.
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