Cited by 105Cancer-related Molecular PathwaysCell death mechanisms and regulationDNA Repair Mechanisms

p53 target gene AEN is a nuclear exonuclease required for p53-dependent apoptosis

Kawase, T, Ichikawa, H, Ohta, T, Nozaki, N, Tashiro, F, Ohki, R, Taya, Y·2008·Oncogene

Abstract

DNA degradation is one of the biochemical hallmarks detected in apoptotic cells, and several nucleases have been reported to function cooperatively in this process. It has also been suggested that different sets of nucleases are activated by different stimuli, and induce distinct patterns of DNA degradation. Here we report that apoptosis-enhancing nuclease (AEN) is a novel direct target gene of p53. AEN is induced by p53 with various DNA damage, and its expression is regulated by the phosphorylation status of p53. We demonstrate that AEN is a typical exonuclease with conserved exonuclease domains Exo I-III, and it targets both single- and double-stranded DNA and RNA. AEN induces apoptosis by itself, and the conserved domains are essential for both AEN nuclease activity and its apoptosis-inducing ability. AEN possesses nuclear and nucleolar localization signals, and it translocates from the nucleolus to nucleoplasm upon apoptosis induction. We also show the dislocation of nucleophosmin in conjunction with the translocation of AEN to the nucleoplasm, indicating the ability of AEN in nucleolus disruption. In addition, AEN is shown to be required for efficient DNA fragmentation in p53-dependent apoptosis. These results suggest that AEN is an important downstream mediator of p53 in apoptosis induction.

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Crossref · 10.1038/onc.2008.32

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  • The p53 target gene AEN encodes for an apoptosis-enhancing nuclease that further supports apoptosis through digestion of double-stranded DNA.

    “The p53 target gene AEN encodes for an apoptosis-enhancing nuclease that further supports apoptosis through digestion of double-stranded DNA.44”

    From Census and evaluation of p53 target genes (2017) · cites this paper as [44]

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Authors
Kawase, T., Ichikawa, H., Ohta, T., Nozaki, N., Tashiro, F., Ohki, R., & Taya, Y.
Affiliations
  • National Cancer Center Research Institute (JP)
  • Kanagawa Dental University (JP)
  • Tokyo University of Science (JP)
  • Japan Science and Technology Agency (JP)
Corresponding author
  • Ohki, R
  • Taya, Y
Venue
Oncogene
Published
2008-02-11
Volume
27
Issue
27
Pages
3797-3810
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
OpenAlex
W1998743183
Cited by
105
References
41
Citations by year
2026: 7 · 2025: 4 · 2024: 11 · 2023: 13 · 2022: 9 · 2021: 12 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 3
FWCI
2.11
Type
journal article
Language
en
Open access
closed
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
AEN, p53 target genes, p53-dependent apoptosis, exonuclease activity, DNA fragmentation, p53 phosphorylation, nucleolus, nucleophosmin, DNA damage response, nucleic acid degradation
MeSH terms
DNA Damage, Exodeoxyribonucleases, Exonucleases, Humans, Kinetics, Mutation, Neoplasms, Phosphorylation, Gene Expression Regulation, Enzymologic, Genes, p53, Tumor Suppressor Protein p53, Apoptosis, DNA Fragmentation

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