The Lim-only protein LMO4 modulates the transcriptional activity of HEN1

The Lim-only protein LMO4 modulates the transcriptional activity of HEN1
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DOI:
10.1016/s0006-291x(03)01298-1
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发表时间:
2003-08-08
影响因子:
3.1
通讯作者:
Axelson, H
Axelson, H
中科院分区:
生物学4区
文献类型:
--
作者:
Manetopoulos, C;Hansson, A;Axelson, H

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碱性螺旋-环-螺旋蛋白HEN 1和仅LIM蛋白LMO 2和LMO 4在神经元细胞中表达。HEN 1是由于其与TAL 1的同源性而克隆的,TAL 1是一种对早期造血重要的bHLH蛋白。由于已经显示TAL 1与红细胞和白血病细胞中的LMO蛋白形成复合物,我们研究了HEN 1与LMO 2和LMO 4形成复合物的能力。通过哺乳动物双杂交分析,我们表明HEN 1与LMO 2和LMO 4都相互作用。为了表征HEN I单独或与LMO 2和LMO 4一起的转录能力,我们进行了报告基因测定。与广泛表达的bHLH蛋白E47相比,HEN 1是一种非常温和的转录激活因子,滴定实验表明,HEN 1与TAL 1一样,抑制E47介导的转录激活。此外,LMO 4而不是LMO 2能够增强这种效果。HEN 1在海马前体细胞中的过表达导致神经突延伸,这可以被LMO 4阻止。总之,这些结果表明,LMO蛋白可以调节HEN 1的转录活性。(C)2003年爱思唯尔公司All rights reserved.
The basic helix-loop-helix protein HEN1 and the LIM-only proteins LMO2 and LMO4 are expressed in neuronal cells. HEN1 was cloned by virtue of its homology to TAL1, a bHLH protein important for early hematopoiesis. Since it has been shown that TAL1 forms complex with LMO proteins in erythroid and leukemic cells we investigated the capacity of HEN1 to form complex with LMO2 and LMO4. By mammalian two-hybrid analysis, we show that HEN1 interacts with both LMO2 and LMO4. To characterize the transcriptional capacity of HEN I alone or together with LMO2 and LMO4, we performed reporter gene assays. In comparison with the ubiquitously expressed bHLH protein E47, HEN1 is a very modest transcriptional activator and titration experiments indicate that HEN1, like TAL1, represses E47 mediated transcriptional activation. Furthermore, LMO4 but not LMO2 was able to augment this effect. Overexpression of HEN1 in hippocampal precursor cells resulted in neurite extension, which could be prevented by LMO4. Taken together, these results indicate that LMO proteins can modulate the transcriptional activity of HEN1. (C) 2003 Elsevier Inc. All rights reserved.