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Title:
The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage | Journal of Human Genetics
Description:
The tumor suppressor p53 plays a crucial role in the cellular response to DNA damage by transcriptional activation of numerous downstream genes. Although a considerable number of p53 target genes have been reported, the precise mechanism of p53-regulated tumor suppression still remains to be elucidated. Here, we report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell death. The DFNA5 gene has been previously reported to be responsible for autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5 gene was strongly induced by exogenous and endogenous p53. The chromatin immunoprecipitation assay indicated that a potential p53-binding sequence is located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay revealed that the sequence displays p53-dependent transcriptional activity. The ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence of p53; however, it was inhibited in the absence of p53. Finally, the expression of DFNA5 mRNA was remarkably induced by gamma-ray irradiation in the colon of p53(+/+) mice but not in that of p53(โ/โ) mice. These results suggest that DFNA5 plays a role in the p53-regulated cellular response to genotoxic stress probably by cooperating with p53.
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Keywords {๐}
dfna, cells, expression, cell, gene, dna, article, google, scholar, cas, fig, response, pbs, cancer, protein, role, damage, apoptosis, analysis, mrna, nature, cellular, mice, hearing, function, human, impairment, death, assay, pdependent, antibody, nakamura, arakawa, etoposideinduced, hepg, wildtype, genes, pregulated, line, apoptotic, target, pwaf, infected, van, mutant, sequences, reported, sequence, presence, results,
Topics {โ๏ธ}
nature portfolio si-mscv-puro-h1r-p53ri retrovirus permissions reprints privacy policy si-mscv-puro-h1r retrovirus open reading frame mrna purification kits advertising include cell-cycle-regulating proteins nature 404 nature 408 nature p53-dependent cell-cycle checkpoint pcr-blunt ii-topo plasmid etoposide-resistant mewo-eto-1 cells social media pcr-blunt ii-topo etoposide-induced cell death author information authors p53-inducible ubiquitin-protein ligase genotoxin-induced cell death parental mewo-eto-1 cells semi-quantitative rt-pcr analysis tumor suppressor p53 etoposide-induced dna damage dna damage-induced apoptosis author correspondence predictive p53 binding-sites brain-specific p53-target gene p53-regulated tumor suppression dna damage-repair proteins hiroshi egamiย &ย hideo baba induce p53-dependent apoptosis induce p53-dependent apotosis ecori-digested dna fragment hepg2-p53-cont cells subjected lung-cancer cell line consensus p53-binding sequence regulates p53-dependent apoptosis gsdme-mediated pyroptosis promotes semi-quantitative rt-pcr 4ย mg/ml bromophenol blue gamma-irradiation-induced apoptosis mouse anti-flag antibody etoposide-induced apoptotic cells p53-dependent apoptotic pathway g418-resistant colonies grown p53-independent ceramide formation pyroptosis cell death p53-mediated cellular response
Questions {โ}
- Furthermore, does DFNA5 mediate the p53-regulated cellular response outside the cochlea?
- How do we explain such contrasting dual roles of DFNA5 in the cellular response to DNA damage?
- The most important question is how and where does DFNA5 function as a mediator of p53?
- Van Laer L, Vrijiens K, Thys S et al (2004) DFNA5: hearing impairment exon instead of hearing impairment gene?
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datePublished:2006-08-01T00:00:00Z
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p53
Tumor suppressor gene
Hearing impairment
DNA damage
Cell death
Apoptosis
Etoposide
p53 target gene
Human Genetics
Molecular Medicine
Gene Function
Gene Expression
Gene Therapy
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headline:The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage
description:The tumor suppressor p53 plays a crucial role in the cellular response to DNA damage by transcriptional activation of numerous downstream genes. Although a considerable number of p53 target genes have been reported, the precise mechanism of p53-regulated tumor suppression still remains to be elucidated. Here, we report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell death. The DFNA5 gene has been previously reported to be responsible for autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5 gene was strongly induced by exogenous and endogenous p53. The chromatin immunoprecipitation assay indicated that a potential p53-binding sequence is located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay revealed that the sequence displays p53-dependent transcriptional activity. The ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence of p53; however, it was inhibited in the absence of p53. Finally, the expression of DFNA5 mRNA was remarkably induced by gamma-ray irradiation in the colon of p53(+/+) mice but not in that of p53(รขยย/รขยย) mice. These results suggest that DFNA5 plays a role in the p53-regulated cellular response to genotoxic stress probably by cooperating with p53.
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Tumor suppressor gene
Hearing impairment
DNA damage
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p53 target gene
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Gene Function
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