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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), which binds to p53 protein specifically enhances its pro-apoptotic function, thus exerting a tumor suppressive effect.We found that one of the more than 300 N In this study, we constructed rAd-ASPP2, rAd-ΔASPP2 adenovirus, the use of rAd-p53, rAd-ASPP2, rAd- AASPP2 infected p53-deficient cell line H1299 and investigated the effect of ASPP2 and ΔASPP2 on p53-mediated apoptosis by MMS, and found that overexpression of p53 can significantly promote the apoptosis of tumor cells; ASPP2 can significantly enhance the expression of p53 However, AASPP2 had no significant effect on p53-mediated apoptosis but significantly inhibited the pro-apoptotic effect of rAd-ASPP2-enhanced rAd-p53.p53-ASPP2-complex Body may change the conformation of p53 protein and promote the binding activity of p53 and enhancer Bax.Expression of p53 transcriptional regulation gene expression study showed that the presence of ΔASPP2 could significantly inhibit ASPP2 enhanced p53-mediated bax gene transcription activity, suggesting that ΔASPP2 may be associated with ASPP2 Later engagement inhibit apoptosis gene transcription activity of p53.