Stimulation of the murine Uchl1 gene promoter by the B-Myb transcription factor
Stimulation of the murine Uchl1 gene promoter by the B-Myb transcription factor
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DOI：
10.1016/s0169-5002(03)00279-4
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发表时间：
2003-10-01
期刊：
影响因子：
5.3
通讯作者：
Gray, DA
中科院分区：
文献类型：
--
作者：
Long, EM;Long, MA;Gray, DA
据报道，人肺癌经常过表达普遍存在的细胞周期转录因子B-myb和泛素羧基末端水解酶UCHL 1，UCHL 1是一种表达通常限于肺中的神经元和神经内分泌细胞的酶。这些标记物共表达的一个可能的解释是Uchl 1受B-Myb的转录调控，并且在肿瘤中UCHL 1的异位表达是B-Myb过表达的直接结果。我们在小鼠模型系统中通过克隆小鼠Uchl 1启动子并分析其受小鼠B-Myb的调控来验证这一假设。共转染的B-Myb诱导Uchl 1启动子驱动的荧光素酶报告基因的表达，但诱导不依赖于启动子区域中鉴定的myb共识结合位点的存在。正如其他基因所报道的那样，B-Myb的诱导取决于Uchl 1 TATA盒的背景。在肺上皮中表达截短的组成型活性形式的B-Myb的转基因小鼠显示UCHL 1蛋白的表达升高。我们的结论是，B-Myb可以刺激Uchl 1在培养细胞和体内的表达。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
It has been reported that human lung cancers frequently overexpress both the ubiquitous cell cycle transcription factor B-myb and the ubiquitin carboxyterminal hydrolase UCHL1, an enzyme whose expression is normally limited to neurons and neuroendocrine cells in the lung. A possible explanation for the co-expression of these markers is that Uchl1 is subject to transcriptional regulation by B-Myb, and in tumors the ectopic expression of UCHL1 is a direct consequence of B-Myb overexpression. We have tested this hypothesis in the mouse model system by cloning the murine Uchl1 promoter and analyzing its regulation by murine B-Myb. Expression of a Luciferase reporter gene driven by the Uchl1 promoter was induced by cotransfected B-Myb, but induction was not dependent on the presence of a myb consensus binding site identified in the promoter region. B-Myb induction was dependent on the context of the Uchl1 TATA box, as has been reported for other genes. Transgenic mice expressing a truncated, constitutively active form of B-Myb in the lung epithelium showed elevated expression of UCHL1 protein. We conclude that B-Myb can stimulate expression of the Uchl1 both in cultured cells and in vivo. (C) 2003 Elsevier Ireland Ltd. All rights reserved.