Upstream stimulating factor-1 (USF1) and USF2 bind to and activate the promoter of the Adenomatous polyposis coli (APC) tumor suppressor gene
Upstream stimulating factor-1 (USF1) and USF2 bind to and activate the promoter of the Adenomatous polyposis coli (APC) tumor suppressor gene
复制标题
DOI：
10.1002/1097-4644(20010501)81:2
复制
发表时间：
2001-01-01
影响因子：
4
通讯作者：
Narayan, S
中科院分区：
文献类型：
--
作者：
Jaiswal, AS;Narayan, S
腺瘤性大肠杆菌 (APC) 基因产物参与细胞周期停滞和细胞凋亡，功能丧失与结直肠癌的发生有关。尽管已证明APC基因是可诱导的，但其转录调控尚未阐明。因此，我们对 APC 基因的启动子区域和基础表达所需的转录因子进行了表征。 APC 基因具有无 TATA 的启动子，并包含八聚体、AP2、Sp1、CAAT 盒的共有结合位点以及 E 盒 A、B 和 M 的三个核苷酸序列。E 盒在多种癌细胞系中发挥作用，上游刺激因子 1 (USF1) 和 USF2 与这些位点相互作用，对 B 位点具有优选的序列特异性。在 HCT-116 细胞中瞬时转染测定中，对 USF1 和 USF2 对克隆的 APC 启动子的激活进行分析表明，E-box B 位点的突变完全消除了基础启动子活性。此外，具有 E-box A、B 和 M 位点缺失突变的 HCT-116 细胞中 USF1 和 USF2 的异位表达表明，这些 E-box 有助于 USF1 和 USF2 介导的 APC 启动子转录激活，最大启动子活性与 E-box B 位点相关。因此，USF1和USF2转录因子对于APC基因表达至关重要。 (C) 2001 Wiley-Liss, Inc.
The adenomatous polyposis coli (APC) gene product is involved in cell cycle arrest and apoptosis, and loss of function is associated with the development of colorectal carcinogenesis. Although it has been demonstrated that the APC gene is inducible, its transcriptional regulation has not been elucidated. Therefore, we characterized the promoter region of the APC gene and transcription factors required for basal expression. The APC gene has a TATA-less promoter and contains consensus binding sites for Octamer, AP2, Sp1, a CAAT-box, and three nucleotide sequences for E-box A, B, and M. The E-boxes are functional in several cancer cell lines and upstream stimulating factor-1 (USF1) and USF2 interact with these sites, with a preferred sequence-specificity for the B site. Analysis of activation of the cloned APC promoter by USF1 and USF2 in transient transfection assays in HCT-116 cells demonstrated that mutation of the E- box B site completely abolished the basal promoter activity. Further, the ectopic USF1 and USF2 expression in HCT-116 cells with deletion mutations of E-box A, B, and M sites showed that these E-boxes contribute to USF1- and USF2-mediated transcriptional activation of the APC promoter, with maximum promoter activity being associated with the E-box B site. Thus, USF1 and USF2 transcription factors are critical for APC gene expression. (C) 2001 Wiley-Liss, Inc.