Exonuclease with activity against single- and double-stranded DNA and RNA. Mediates p53-induced apoptosis. When induced by p53 following DNA damage, digests double-stranded DNA to form single-stranded DNA and amplifies DNA damage signals, leading to enhancement of apoptosis.
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.
To investigate ionizing radiation response, we screened genes that exhibit higher expression following gamma irradiation. We report here the isolation and functional characterization of a novel ionizing radiation-induced gene, AEN. Sequence analysis of AEN revealed exonuclease domain highly similar to that of exonuclease III. The AEN protein revealed DNase activity by cleaving various DNA substrates. Subcellular distribution of AEN exhibited nuclear colocalization with apoptotic nucleases such as CAD and AIF following irradiation. Moreover AEN distribution revealed perinuclear staining pattern which could be seen with other apoptotic nucleases. Irradiation of AEN-expressing cells resulted in synergistic increase of apoptosis whereas AEN deletion mutant in exonuclease domain did not. Our data, thus, suggest that radiation-induced AEN cleaves DNA in concert with other apoptotic nucleases and thereby enhances apoptosis following ionizing irradiation.
To investigate ionizing radiation response, we screened genes that exhibit higher expression following gamma irradiation. We report here the isolation and functional characterization of a novel ionizing radiation-induced gene, AEN. Sequence analysis of AEN revealed exonuclease domain highly similar to that of exonuclease III. The AEN protein revealed DNase activity by cleaving various DNA substrates. Subcellular distribution of AEN exhibited nuclear colocalization with apoptotic nucleases such as CAD and AIF following irradiation. Moreover AEN distribution revealed perinuclear staining pattern which could be seen with other apoptotic nucleases. Irradiation of AEN-expressing cells resulted in synergistic increase of apoptosis whereas AEN deletion mutant in exonuclease domain did not. Our data, thus, suggest that radiation-induced AEN cleaves DNA in concert with other apoptotic nucleases and thereby enhances apoptosis following ionizing irradiation.
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.
Interacting selectively and non-covalently with any nucleic acid.
IEAInterPro 2 GO
GO biological process
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:0042771]
A series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage, and ends when the execution phase of apoptosis is triggered.
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.
Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a ionizing radiation stimulus. Ionizing radiation is radiation with sufficient energy to remove electrons from atoms and may arise from spontaneous decay of unstable isotopes, resulting in alpha and beta particles and gamma rays. Ionizing radiation also includes X-rays.
To investigate ionizing radiation response, we screened genes that exhibit higher expression following gamma irradiation. We report here the isolation and functional characterization of a novel ionizing radiation-induced gene, AEN. Sequence analysis of AEN revealed exonuclease domain highly similar to that of exonuclease III. The AEN protein revealed DNase activity by cleaving various DNA substrates. Subcellular distribution of AEN exhibited nuclear colocalization with apoptotic nucleases such as CAD and AIF following irradiation. Moreover AEN distribution revealed perinuclear staining pattern which could be seen with other apoptotic nucleases. Irradiation of AEN-expressing cells resulted in synergistic increase of apoptosis whereas AEN deletion mutant in exonuclease domain did not. Our data, thus, suggest that radiation-induced AEN cleaves DNA in concert with other apoptotic nucleases and thereby enhances apoptosis following ionizing irradiation.
Protein involved in apoptotic programmed cell death. Apoptosis is characterized by cell morphological changes, including blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation and chromosomal DNA fragmentation, and eventually death. Unlike necrosis, apoptosis produces cell fragments, called apoptotic bodies, that phagocytic cells are able to engulf and quickly remove before the contents of the cell can spill out onto surrounding cells and cause damage. In general, apoptosis confers advantages during an organism's life cycle.
Protein induced by DNA damage or protein involved in the response to DNA damage. Drug- or radiation-induced injuries in DNA introduce deviations from its normal double-helical conformation. These changes include structural distortions which interfere with replication and transcription, as well as point mutations which disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. Response to DNA damage results in either repair or tolerance.
Enzyme which catalyzes hydrolysis reaction, i.e. the addition of the hydrogen and hydroxyl ions of water to a molecule with its consequent splitting into two or more simpler molecules.
Enzyme that degrades nucleic acids into shorter oligonucleotides or single nucleotide subunits by hydrolyzing sugar-phosphate bonds in the nucleic acid backbone.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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