ArticlePloS one2013
Dual regulatory roles of human AP-endonuclease (APE1/Ref-1) in CDKN1A/p21 expression.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation.Expert opinion on therapeutic targets · 2026Review
- Role of APE1/Ref-1 in hydrogen peroxide-induced apoptosis in human renal HK-2 cells.Kidney research and clinical practice · 2024Article
- Levels of APE1 Repair Gene and CLEC4M in Lung Cancer Patients Receiving Cisplatin Chemotherapy.Archives of Razi Institute · 2023Article
- Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation.Cancers · 2021Review
- Exploring the Role of Non-Coding RNAs in the Pathophysiology of Systemic Lupus Erythematosus.Biomolecules · 2020Review
- Review
- Targeting Histone Chaperone FACT Complex Overcomes 5-Fluorouracil Resistance in Colon Cancer.Molecular cancer therapeutics · 2020Article
- Defenses against Pro-oxidant Forces - Maintenance of Cellular and Genomic Integrity and Longevity.Radiation research · 2018Review
- APE1/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells.Oncotarget · 2018Article
- The Role of Long Non-coding RNAs in the Pathogenesis of RA, SLE, and SS.Frontiers in medicine · 2018Article
- The extracellular role of DNA damage repair protein APE1 in regulation of IL-6 expression.Cellular signalling · 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
- Microarray analysis of differential gene expression profiles in blood cells of naturally BLV-infected and uninfected Holstein-Friesian cows.Molecular biology reports · 2017Article
- Article
- Regulation of limited N-terminal proteolysis of APE1 in tumor via acetylation and its role in cell proliferation.Oncotarget · 2016Article
- Endothelial cell tumor growth is Ape/ref-1 dependent.American journal of physiology. Cell physiology · 2015Article
- New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.Cellular and molecular life sciences : CMLS · 2015Review
- Apurinic/apyrimidinic endonuclease/redox factor-1 (APE1/Ref-1) redox function negatively regulates NRF2.The Journal of biological chemistry · 2015Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The human AP-endonuclease (APE1/Ref-1), an essential multifunctional protein involved in repair of oxidative DNA damage as well as in transcriptional regulation, is often overexpressed in tumor cells. APE1 was earlier shown to stimulate p53's DNA binding and its transactivation function in the expression of cyclin-dependent kinase inhibitor p21 (CDKN1A) gene. Here, we show APE1's stable binding to p53 cis elements which are required for p53-mediated activation of p21 in p53-expressing wild type HCT116 cells. However, surprisingly, we observed APE1-dependent repression of p21 in isogenic p53-null HCT116 cells. Ectopic expression of p53 in the p53-null cells abrogated this repression suggesting that APE1's negative regulatory role in p21 expression is dependent on the p53 status. We then identified APE1's another binding site in p21's proximal promoter region containing cis elements for AP4, a repressor of p21. Interestingly, APE1 and AP4 showed mutual dependence for p21 repression. Moreover, ectopic p53 in p53-null cells inhibited AP4's association with APE1, their binding to the promoter and p21 repression. These results together establish APE1's role as a co-activator or co-repressor of p21 gene, dependent on p53 status. It is thus likely that APE1 overexpression and inactivation of p53, often observed in tumor cells, promote tumor cell proliferation by constitutively downregulating p21 expression.
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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.