异构体ΔASPP2可拮抗ASPP2对p53(细胞)凋亡功能的增强作用  

The Isomer ΔASPP2 Abrogates ASPP2-promoted p53 Apoptosis

作　　者：丁渭 侯庆生[2] 王东阳[3] 刘凯 夏海滨[3] 石英 陈德喜 

机构地区：[1]北京佑安医院北京市肝病研究所,北京100054 [2]山东省肿瘤医院消化道肿瘤外科,济南250117 [3]陕西师范大学生命科学学院基因治疗研究室,西安710062

出　　处：《中国生物化学与分子生物学报》2012年第2期133-139,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然基金(No.81071843;No.30910103915;No.81100288和No.30870853)资助项目~~

摘　　要：p53凋亡刺激蛋白2(apoptosis stimulating protein 2 of p53,ASPP2)能够与p53蛋白结合特异性地增强其促细胞凋亡功能,进而发挥肿瘤抑制作用.我们发现的1个比ASPP2少300多个N端氨基酸的异构体ΔASPP2.目前,ΔASPP2对p53起何种作用尚不清楚.在本研究中,我们构建了rAd-ASPP2、rAd-ΔASPP2腺病毒,利用rAd-p53、rAd-ASPP2、rAd-ΔASPP2感染p53缺失的细胞系H1299,在MMS的作用下研究ASPP2和ΔASPP2对p53介导的细胞凋亡的影响.结果发现,p53自身过表达能明显促进肿瘤细胞的凋亡;ASPP2可显著增强p53介导的MMS引起的H1299细胞凋亡的作用;然而,ΔASPP2对p53介导的细胞凋亡没有明显影响但却显著抑制rAd-ASPP2增强的rAd-p53的促细胞凋亡作用.p53-ASPP2复合体可能改变p53蛋白的构象,促进p53和增强子Bax的结合活性.p53转录调控基因的表达研究显示,ΔASPP2的存在可显著抑制ASPP2增强p53介导的bax基因转录活性,提示ΔASPP2可能与ASPP2结合后来抑制p53的凋亡基因转录活性.Apoptosis stimulating protein 2 of p53（ASPP2） interacts with p53 and specifically enhances p53-induced apoptosis to suppress tumor growth.ΔASPP2 is an isoform of ASPP2,which contains 300 amino acid residues shorter than ASPP2 at N-terminal,but how ΔASPP2 interacts with p53 remains unclear.In this study,rAd-ASPP2,rAd-ΔASPP2 adenovirus were constructed and transfected into H1299（p53 deleted cell line） to investigate the interaction of ASPP2 and ΔASPP2 to p53-mediated cell apoptosis.It was found that over-expression of p53 significantly promoted the apoptosis of tumor cells.ASPP2 enhanced the p53 mediated apoptosis of H1299 induced by MMS.ΔASPP2 had no obvious effect on p53-mediated apoptosis,but inversed the enhanced pro-apoptosis of rAd-p53 by rAd-ASPP2.p53-ASPP2 complex may change the conformation of p53 and facilitate the interaction of p53 and Bax.Expression of p53 transcriptional control gene demonstrated that ΔASPP2 suppress transcription of bax mediated by p53,which had been enhanced by ASPP2.The results suggested that ΔASPP2 may interact with ASPP2 and retain the apoptosis gene transcription function of p53.

关 键 词：重组p53腺病毒 p53凋亡刺激蛋白2(ASPP2) ASPP2亚型(ΔASPP2) H1299细胞株 细胞凋亡 

分 类 号：Q291[生物学—细胞生物学]