p53-dependent upregulation of PIG3 transcription by γ-ray irradiation and its interaction with KAP1 in responding to DNA damage  

作　　者：QIN Xia ZHANG ShiMeng LI Bingi LIU XiaoDan HE XingPeng SHANG ZengFu XU QinZhi ZHAO ZengQiang YE QiNong ZHOU PingKun 

机构地区：[1]Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, China [2]College of Public Health, University of South China, Hengyang 421000, China [3]Beijing Institute ofBiotechnology, Beijing 100850, China

出　　处：《Chinese Science Bulletin》2011年第30期3162-3171,共10页

基　　金：supported by the National Basic Research Program of China (2007CB914603);the National Natural Science Foundation of China (30970677);the Outstanding Youth Scientist Foundation of National Natural Science Foundation of China (30825011)

摘　　要：PIG3 (p53-inducible gene 3), originally identified as one of a set of genes induced by p53 before the onset of apoptosis, was assumed to contribute to early cellular response to DNA damage. Here, we studied the relation between p53 status and the increased expression of PIG3 by ionizing radiation (IR), and the related clues regarding the involvement of PIG3 in the cellular response to IR-induced DNA damage signaling. We demonstrated that the pentanucleotide microsatellite sequence was responsible for the p53-dependent induction of PIG3 transcription after irradiation, while sequence upstream of PIG3 promoter could maintain the basal level of expression which was not inducible by irradiation. The interaction of PIG3 and the KRAB-ZFP-associated protein 1 (KAP1), a DNA damage response protein, was revealed. PIG3 nucleus foci were formed 15 min after γ-ray irradiation, and which were found to partially colocalize with the phospho-KAP-1 foci as well as γ-H2AX foci. Although the lac operator tagged EGFP based reporter system revealed that PIG3 does not remodel chromatin in large scale in the cells under normal growing condition, it indeed prompted the chromatin relaxation in the cellular response to DNA damage signaling. All these data suggest that PIG3 is involved in IR-induced DNA damage response, and which maybe partially attribute to its interaction with KAP1.P1G3 （p53-inducible gene 3）, originally identified as one of a set of genes induced by p53 before the onset of apoptosis, was assumed to contribute to early cellular response to DNA damage. Here, we studied the relation between p53 status and the increased expression of PIG3 by ionizing radiation （IR）, and the related clues regarding the involvement of PIG3 in the cellular response to IR-induced DNA damage signaling. We demonstrated that the pentanucleotide microsatellite sequence was responsible for the p53-dependent induction of PIG3 transcription after irradiation, while sequence upstream of PIG3 promoter could maintain the basal level of expression which was not inducible by irradiation. The interaction of PIG3 and the KRAB-ZFP-associated protein 1 （KAP1）, a DNA damage response protein, was revealed. PIG3 nucleus foci were formed 15 min after ＂/-ray irradiation, and which were found to partially colocalize with the phospho-KAP-1 foci as well as γ-H2AX foci. Although the lac operator tagged EGFP based reporter system revealed that PIG3 does not remodel chromatin in large scale in the cells under normal growing condition, it indeed prompted the chromatin relaxation in the cellular response to DNA damage signaling. All these data suggest that PIG3 is involved in IR-induced DNA damage response, and which maybe partially attribute to its interaction with KAP1.

关 键 词：DNA损伤 射线照射 p53 转录 依赖性 诱导基因 细胞反应 染色质重塑 

分 类 号：R363[医药卫生—病理学]