Multifunctional transcription factor TFII-I is an activator of BRCA1 function.
Multifunctional transcription factor TFII-I is an activator of BRCA1 function.
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DOI：
10.1038/bjc.2011.75
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发表时间：
2011-04-12
影响因子：
8.8
通讯作者：
Taketani, Y.
中科院分区：
文献类型：
--
作者：
Tanikawa, M.;Wada-Hiraike, O.;Nakagawa, S.;Shirane, A.;Hiraike, H.;Koyama, S.;Miyamoto, Y.;Sone, K.;Tsuruga, T.;Nagasaka, K.;Matsumoto, Y.;Ikeda, Y.;Shoji, K.;Oda, K.;Fukuhara, H.;Nakagawa, K.;Kato, S.;Yano, T.;Taketani, Y.
TFII-I是一种多功能转录因子，已知其特异性结合几种DNA序列元件并介导生长因子信号传导。编码TFII-I和相关转录因子家族的染色体位置7q11.23处的微缺失可能导致Williams-Beuren综合征的发作，Williams-Beuren综合征是一种常染色体显性遗传疾病，其特征为独特的认知特征、糖尿病、高血压、焦虑和颅面缺陷。遗传性乳腺癌和卵巢癌易感基因产物BRCA 1已被证明是通过结合SIRT 1的启动子区域而作为SIRT 1表达的正调节因子，但迄今为止尚未研究BRCA 1和TFII-I之间的串扰。探讨了TFII-I和BRCA 1之间的物理相互作用。为了确定TFII-I的病理生理功能，研究了其作为BRCA 1的转录辅因子的作用。我们发现TFII-I的羧基末端和BRCA 1的羧基末端之间存在物理相互作用，也称为BRCT结构域。内源性TFII-I和BRCA 1在完整细胞的细胞核中形成复合物，并观察到辐射诱导的核灶的形成。我们还表明，TFII-I的表达刺激BRCT的转录激活功能的瞬时表达测定。TFII-I的表达也增强了全长BRCA 1介导的SIRT 1启动子的转录激活。这些结果揭示了TFII-I调节BRCA 1细胞功能的内在机制，为了解乳腺癌的发生发展提供了重要的意义。
The TFII-I is a multifunctional transcriptional factor known to bind specifically to several DNA sequence elements and to mediate growth factor signalling. A microdeletion at the chromosomal location 7q11.23 encoding TFII-I and the related family of transcription factors may result in the onset of Williams–Beuren syndrome, an autosomal dominant genetic disorder characterised by a unique cognitive profile, diabetes, hypertension, anxiety, and craniofacial defects. Hereditary breast and ovarian cancer susceptibility gene product BRCA1 has been shown to serve as a positive regulator of SIRT1 expression by binding to the promoter region of SIRT1, but cross talk between BRCA1 and TFII-I has not been investigated to date. A physical interaction between TFII-I and BRCA1 was explored. To determine pathophysiological function of TFII-I, its role as a transcriptional cofactor for BRCA1 was investigated. We found a physical interaction between the carboxyl terminus of TFII-I and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous TFII-I and BRCA1 form a complex in nuclei of intact cells and formation of irradiation-induced nuclear foci was observed. We also showed that the expression of TFII-I stimulates the transcriptional activation function of BRCT by a transient expression assay. The expression of TFII-I also enhanced the transcriptional activation of the SIRT1 promoter mediated by full-length BRCA1. These results revealed the intrinsic mechanism that TFII-I may modulate the cellular functions of BRCA1, and provide important implications to understand the development of breast cancer.
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影响因子：
8
作者：
Wada, O;Oishi, H;Kato, S
通讯作者：
Kato, S
DOI：
10.1073/pnas.94.11.5820
发表时间：
1997-05-27
影响因子：
11.1
作者：
Humphrey, JS;Salim, A;Klausner, RD
通讯作者：
Klausner, RD
影响因子：
4.8
作者：
Wen, YD;Cress, WD;Seto, E
通讯作者：
Seto, E
DOI：
10.1073/pnas.93.24.13595
发表时间：
1996-11-26
影响因子：
11.1
作者：
Monteiro, ANA;August, A;Hanafusa, H
通讯作者：
Hanafusa, H
影响因子：
16
作者：
Wang, Rui-Hong;Zheng, Yin;Kim, Hyun-Seok;Xu, Xiaoling;Cao, Liu;Luhasen, Tyler;Lee, Mi-Hye;Xiao, Cuiying;Vassilopoulos, Athanassios;Chen, Weiping;Gardner, Kevin;Man, Yan-Gao;Hung, Mien-Chie;Finkel, Toren;Deng, Chu-Xia
通讯作者：
Deng, Chu-Xia