文章基本信息

标题：Comprehensive Search for X-ray-responsive Elements and Binding Factors in the Regulatory Region of the GADD45a Gene
其他标题：Comprehensive Search for X-ray-responsive Elements and Binding Factors in the Regulatory Region of the GADD45a Gene
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作者：KAZUHIRO DAINO ; SACHIKO ICHIMURA ; MITSURU NENOI 等
期刊名称：Journal of Radiation Research
印刷版ISSN：0449-3060
电子版ISSN：1349-9157
出版年度：2003
卷号：44
期号：4
页码：311-318
DOI：10.1269/jrr.44.311
摘要：The growth arrest and DNA damage-inducible protein 45alpha ( GADD45a ) gene is responsive to a variety of DNA-damaging agents. It is known that induction of the GADD45a gene is regulated in a p53-dependent manner after ionizing irradiation. Our previous study showed that X-ray irradiation increased the transcription rate of the GADD45a gene much earlier than the maximum accumulation of stabilized p53 protein in human myeloblastic leukemia ML-1 cells. We hypothesized that some transcription factor(s) may cooperate with p53 in regulating the GADD45a gene early after the irradiation of ML-1 cells. This idea is supported by recent studies showing that the p53-dependent activation of several genes in human and mouse cells requires some additional transcription factors, such as Sp1, GKLF, Ets1, and IRF-1. To examine the possible involvement of cooperating factors in transcriptional regulation of the GADD45a gene by ionizing radiation, we comprehensively searched for the X-ray-inducible binding locus of the nuclear factor throughout the upstream region (-2244 bp/ 89 bp) and the third intron ( 1389 bp/ 2488 bp) of the GADD45a gene by EMSA using 136 probes. The X-ray-responsive binding of nuclear factors was detected at eight loci. Oct, NF-κB, HNF, NF-AT, and KLF family transcription factors were identified by a competition assay. It is possible that some of these factors cooperate with p53 to mediate transcriptional regulation of the GADD45a gene after ionizing irradiation.
关键词：X-ray-responsive element;Transcription factor;X-ray irradiation;Myeloblastic leukemia cells