中文摘要：

BATF2/SARI是一种新发现的转录因子,具有与BATF和BATF3类似的碱性亮氨酸拉链结构,可抑制AP-1转录因子家族（AP-1 transcription factors）活性,从而发挥抑癌作用.但目前关于BATF2表达调节与功能尚不十分清楚.本研究证明,BATF2通过抑制p53相关的NF-κB活性诱导细胞凋亡.实时定量PCR检测mRNA揭示,BATF2/SARI在p53-野生型的A549、HeLa细胞高水平表达,但在p53-缺失型的H1299细胞表达较低.基因转染结合MTT法、TUNEL法显示,过表达BATF2可诱导凋亡,抑制肿瘤细胞增殖;这种抑制效应与细胞p53表达水平相关.采用含NF-κB或AP-1结合位点的（人工合成）启动子驱动的荧光素酶报告基因活性分析发现,过表达BATF2既可抑制AP-1,又可抑制NF-κB转录活性;抑制NF-κB活性与细胞p53状态有关.RNA干扰敲减A549、HeLa细胞的p53表达可消除过表达外源BATF2引起的NF-κB活性下降.本研究结果提示,BATF2通过抑制NF-κB及AP-1转录活性诱导凋亡,从而抑制细胞增殖;BATF2对NF-κB活性的抑制作用依赖p53.因此,BATF2作为一种抑癌基因产物,其作用机制可能比当前的认识和预期更为复杂.

英文摘要：

Human BATF2/SARI is a novel tumor suppressor gene,which contains a basic leucine zipper protein domain as BATF and BATF3.Except for the suppression of interferon-beta induced AP-1 transcription activities,the functional characteristics and the anti-tumor mechanism of BATF2 are largely unknown.In this study,we demonstrate that BATF2 induces apoptosis of tumor cells by inhibiting p53-associated NF-κB activity.Real-time quantitative PCR（RT-qPCR） showed that BATF2 was highly expressed in A549（p53-wild-type） and HeLa（p53-wild-type） cells but lower in H1299（p53-null） cells.Combination of gene transfection with TUNEL and MTT assays revealed that overexpression of BATF2 induced apoptosis,thereby inhibiting cell proliferation,which was correlated to p53 expression.Analyzing the activities of report luciferase,whose expression was driven by regulating sequences containing AP-1 and NF-κB sites,respectively,showed that overexpression of BATF2 inhibited both AP-1 and NF-κB transcriptional activities,in which the BATF2-inhibited effect on NF-κB but not AP-1 activity was related to p53.Knocking-down of p53 by RNA interference in A549 and HeLa cells could abolish the inhibition of NF-κB activities by BATF2.These results indicate that BATF2 can suppress the transcriptional activities of AP-1 and NF-κB to induce apoptosis and inhibit cell proliferation,and that suppression of NF-κB activity by BATF2 is correlated to p53.These data also suggest that the mechanisms underlining BATF2 inhibition of cell growth might be rather sophisticated.