ArticleMolecular and cellular biology2007
ATF4-dependent oxidative induction of the DNA repair enzyme Ape1 counteracts arsenite cytotoxicity and suppresses arsenite-mediated mutagenesis.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- DNA-Protein Cross-Links Derived from Abasic DNA Lesions: Recent Progress and Future Directions.Chemical research in toxicology · 2025Review
- A bioinformatic analysis found low expression and clinical significance of ATF4 in breast cancer.Heliyon · 2024Article
- A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.Frontiers in molecular neuroscience · 2023Review
- Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro.Nucleic acids research · 2022Article
- Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity.Oncoimmunology · 2022Article
- Oxidative DNA damage is concurrently repaired by base excision repair (BER) and apyrimidinic endonuclease 1 (APE1)-initiated nonhomologous end joining (NHEJ) in cortical neurons.Neuropathology and applied neurobiology · 2020Article
- Targeting protein quality control pathways in breast cancer.BMC biology · 2017Review
- Expression of a phosphorylated form of ATF4 in lung and non-small cell lung cancer tissues.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Human AP endonuclease 1: a potential marker for the prediction of environmental carcinogenesis risk.Oxidative medicine and cellular longevity · 2014Review
- ATF4 is directly recruited by TLR4 signaling and positively regulates TLR4-trigged cytokine production in human monocytes.Cellular & molecular immunology · 2013Article
- p300/CBP-associated factor selectively regulates the extinction of conditioned fear.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Functional RNA interference (RNAi) screen identifies system A neutral amino acid transporter 2 (SNAT2) as a mediator of arsenic-induced endoplasmic reticulum stress.The Journal of biological chemistry · 2012Article
- Article
- Activation transcription factor-4 and the acute vascular response to injury.Journal of molecular medicine (Berlin, Germany) · 2010Review
- The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1 phosphorylation in neuronal death.Nature cell biology · 2010Article
- Redox regulation of DNA repair: implications for human health and cancer therapeutic development.Antioxidants & redox signaling · 2010Review
- Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced neuroprotection against global cerebral ischemia.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Ape1/Ref-1 Stimulates GDNF/GFRalpha1-mediated Downstream Signaling and Neuroblastoma Proliferation.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2009Article
- The many functions of APE1/Ref-1: not only a DNA repair enzyme.Antioxidants & redox signaling · 2009Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Arsenite is a human carcinogen causing skin, bladder, and lung tumors, but the cellular mechanisms underlying these effects remain unclear. We investigated expression of the essential base excision DNA repair enzyme apurinic endonuclease 1 (Ape1) in response to sodium arsenite. In mouse 10T(1/2) fibroblasts, Ape1 induction in response to arsenite occurred about equally at the mRNA, protein, and enzyme activity levels. Analysis of the APE1 promoter region revealed an AP-1/CREB binding site essential for arsenite-induced transcriptional activation in both mouse and human cells. Electrophoretic mobility shift assays indicated that an ATF4/c-Jun heterodimer was the responsible transcription factor. RNA interference targeting c-Jun or ATF4 eliminated arsenite-induced APE1 transcription. Suppression of Ape1 or ATF4 sensitized both mouse fibroblasts (10T(1/2)) and human lymphoblastoid cells (TK6) to arsenite cytotoxicity. Expression of Ape1 from a transgene did not efficiently restore arsenite resistance in ATF4-depleted cells but did offset initial accumulation of abasic DNA damage following arsenite treatment. Mutagenesis by arsenite (at the TK and HPRT loci in TK6 cells) was observed only for ATF4-depleted cells, which was strongly offset by Ape1 expression from a transgene. Therefore, the ATF4-mediated up-regulation of Ape1 and other genes plays a key role against arsenite-mediated toxicity and mutagenesis.
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