ArticleOncotarget2016
Regulation of limited N-terminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed.
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- Binding of AP endonuclease-1 to G-quadruplex DNA depends on the N-terminal domain, MgACS bio & med chem Au · 2021Article
- Vitexin inhibits APEX1 to counteract the flow-induced endothelial inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Lysine acetylation of NKG2D ligand Rae-1 stabilizes the protein and sensitizes tumor cells to NKG2D immune surveillance.Cancer letters · 2021Article
- APE1 and SSRP1 is overexpressed in muscle invasive bladder cancer and associated with poor survival.Heliyon · 2021Article
- Functional Role of N-Terminal Extension of Human AP Endonuclease 1 In Coordination of Base Excision DNA Repair via Protein-Protein Interactions.International journal of molecular sciences · 2020Article
- Cleavage of the APE1 N-Terminal Domain in Acute Myeloid Leukemia Cells Is Associated with Proteasomal Activity.Biomolecules · 2020Article
- Targeting Histone Chaperone FACT Complex Overcomes 5-Fluorouracil Resistance in Colon Cancer.Molecular cancer therapeutics · 2020Article
- Acetylation and Deacetylation of DNA Repair Proteins in Cancers.Frontiers in oncology · 2020Review
- APE1 and NPM1 protect cancer cells from platinum compounds cytotoxicity and their expression pattern has a prognostic value in TNBC.Journal of experimental & clinical cancer research : CR · 2019Article
- The Molecular Chaperone Heat Shock Protein 70 Controls Liver Cancer Initiation and Progression by Regulating Adaptive DNA Damage and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathways.Molecular and cellular biology · 2019Article
- Article
- Human AP-endonuclease (Ape1) activity on telomeric G4 structures is modulated by acetylatable lysine residues in the N-terminal sequence.DNA repair · 2019Article
- miR-513a-5p regulates radiosensitivity of osteosarcoma by targeting human apurinic/apyrimidinic endonuclease.Oncotarget · 2018Article
- CREBBP and p300 lysine acetyl transferases in the DNA damage response.Cellular and molecular life sciences : CMLS · 2018Review
- The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression.Cellular signalling · 2017Article
- Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism.Nature communications · 2017Article
- Human Apurinic/Apyrimidinic Endonuclease (APE1) Is Acetylated at DNA Damage Sites in Chromatin, and Acetylation Modulates Its DNA Repair Activity.Molecular and cellular biology · 2017Article
- Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Mammalian apurinic/apyrimidinic (AP) endonuclease 1 (APE1), a ubiquitous and multifunctional protein, plays an essential role in the repair of both endogenous and drug-induced DNA damages in the genome. Unlike its E.coli counterpart Xth, mammalian APE1 has a unique N-terminal domain and possesses both DNA damage repair and transcriptional regulatory functions. Although the overexpression of APE1 in diverse cancer types and the association of APE1 expression with chemotherapy resistance and poor prognosis are well documented, the cellular and molecular mechanisms that alter APE1 functions during tumorigenesis are largely unknown. Here, we show the presence of full-length APE1 and N-terminal truncated isoforms of APE1 in tumor tissue samples of various cancer types. However, primary tumor tissue has higher levels of acetylated APE1 (AcAPE1) as well as full-length APE1 compared to adjacent non-tumor tissue. We found that APE1 is proteolytically cleaved by an unknown serine protease at its N-terminus following residue lysine (Lys) Lys6 and/or Lys7 and after Lys27 and Lys31 or Lys32. Acetylation of these Lys residues in APE1 prevents this proteolysis. The N-terminal domain of APE1 and its acetylation are required for modulation of the expression of hundreds of genes. Importantly, we found that AcAPE1 is essential for sustained cell proliferation. Together, our study demonstrates that increased acetylation levels of APE1 in tumor cells inhibit the limited N-terminal proteolysis of APE1 and thereby maintain the functions of APE1 to promote tumor cells' sustained proliferation and survival.
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