Specificity protein 1 transcription factor regulates human ARTS promoter activity through multiple binding sites.
Specificity protein 1 transcription factor regulates human ARTS promoter activity through multiple binding sites.
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特异性蛋白 1 转录因子通过多个结合位点调节人类 ARTS 启动子活性
DOI：
10.1371/journal.pone.0120072
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Duan Y
中科院分区：
文献类型：
--
作者：
Xu F;Sun W;Li P;Chen J;Zhu D;Sun X;Wang J;Feng J;Song K;Duan Y
TGF-β 信号通路 (ARTS) 中的凋亡相关蛋白是一种不寻常的线粒体 Septin 样蛋白，具有肿瘤抑制因子的功能。来自人类Septin4基因的剪接变体有多种，其中之一是ARTS，也称为Septin4_i2。与Septin4的其他成员不同，ARTS可以诱导许多细胞凋亡，然而，ARTS转录调控的潜在分子机制尚未阐明。在本研究中，我们试图分析培养的 HEK-293T 和 LX-2 细胞中 ARTS 的启动子区域，目的是阐明驱动 ARTS 表达的潜在转录机制。我们有效地证明了 ARTS 启动子的 -824 至 -5 bp 区域对于 ARTS 转录至关重要，并在该核心启动子区域内鉴定了四个假定的特异性蛋白 1 (Sp1) 结合位点。 ChIP 分析表明 Sp1 蛋白可以结合其中两个位点（-735/-718 和 -173/-157），并且每个 Sp1 结合位点的突变导致 ARTS 启动子活性显着降低。总之，所有结果表明Sp1转录因子可能有助于ARTS基因的转录。 ARTS 特定启动子的潜在分子事件也可用于解释为什么 ARTS 在某些人类疾病期间被选择性沉默。这将为进一步研究ARTS对细胞凋亡的作用提供基础。
Apoptosis-related protein in the TGF-β signaling pathway (ARTS) is an unusual mitochondrial Septin-like protein which functions as a tumor suppressor. There are various splice variants derived from the human Septin4 gene, one of which is ARTS, also known as Septin4_i2. Unlike other Septin4 members, ARTS can induce apoptosis in many cells, however, the underlying molecular mechanism for the transcriptional regulation of ARTS has yet to be deciphered. In this study, we attempted to analyze the promoter region of ARTS in cultured HEK-293T and LX-2 cells with the purpose of elucidating the underlying transcriptional mechanisms driving ARTS expression. We effectively demonstrated that the -824 to -5 bp region of the ARTS promoter was essential for ARTS transcription and identified four putative specificity protein 1 (Sp1) binding sites within this core promoter region. ChIP analysis showed that Sp1 protein could bind to two of these sites (-735/-718 and -173/-157) and mutation of each Sp1 binding site led to a significant decrease in ARTS promoter activity. In conclusion, all the results indicated that the Sp1 transcription factor could contribute to ARTS gene transcription. The underlying molecular events of the specific promoter of ARTS could also be used to explain why ARTS is selectively silenced during some human diseases. This would provide basis for further study on the function of ARTS on cell apoptosis.
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影响因子：
3.5
作者：
Peterson EA;Petty EM
通讯作者：
Petty EM
影响因子：
3.7
作者：
Reingewertz TH;Shalev DE;Sukenik S;Blatt O;Rotem-Bamberger S;Lebendiker M;Larisch S;Friedler A
通讯作者：
Friedler A
影响因子：
30.8
作者：
Futscher, BW;Oshiro, MM;Domann, FE
通讯作者：
Domann, FE
影响因子：
12.4
作者：
Edison, N.;Zuri, D.;Larisch, S.
通讯作者：
Larisch, S.
影响因子：
4.5
作者：
Gottfried, Yossi;Rotem, Asaf;Larisch, Sarit
通讯作者：
Larisch, Sarit