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猪Lhx3/LIM-3/P-Lim LIM同源结构域转录因子的特性分析

Characterization of the porcine Lhx3/LIM-3/P-Lim LIM homeodomain transcription factor.

作者信息

Meier B C, Price J R, Parker G E, Bridwell J L, Rhodes S J

机构信息

Department of Biology, Indiana University-Purdue University at Indianapolis, 46202-5132, USA.

出版信息

Mol Cell Endocrinol. 1999 Jan 25;147(1-2):65-74. doi: 10.1016/s0303-7207(98)00213-5.

Abstract

Lhx3/LIM-3/P-Lim is a LIM homeodomain transcription factor which is essential in mice for the development of anterior and intermediate lobes of the pituitary gland. We report the cloning and characterization of porcine Lhx3. The porcine Lhx3 protein exhibits strong similarity to murine Lhx3 within the amino terminal LIM domains and the homeodomain, however, it is diverged in regions outside these motifs. Expression vectors for porcine Lhx3 activated murine and porcine alpha-glycoprotein reporter genes in transfection assays, and recombinant porcine Lhx3 protein specifically bound to a target site within the porcine alpha-glycoprotein gene upstream sequence. In addition, porcine Lhx3 synergistically induced transcription from prolactin enhancer/promoter reporter genes in cooperation with the Pit-1 pituitary transcription factor. Porcine Lhx3 protein interacted with Pit-1 protein in solution and also with the LIM domain-binding protein NLI/Lbd1/CLIM. Together, these data indicate that many aspects of Lhx3 function in the mammalian pituitary are conserved and that Lhx3 may be involved in the activation of trophic hormone genes during early and late stages of pituitary organogenesis. Divergence in the Lhx3 amino acid sequence between mammalian species may suggest distinct activities for this protein in some species and may help identify important functional domains of this key developmental transcription factor.

摘要

Lhx3/LIM-3/P-Lim是一种LIM同源结构域转录因子,对小鼠垂体前叶和中叶的发育至关重要。我们报告了猪Lhx3的克隆和特征。猪Lhx3蛋白在氨基末端LIM结构域和同源结构域内与小鼠Lhx3表现出高度相似性,然而,在这些基序之外的区域存在差异。在转染实验中,猪Lhx3的表达载体激活了小鼠和猪的α-糖蛋白报告基因,重组猪Lhx3蛋白特异性结合到猪α-糖蛋白基因上游序列内的一个靶位点。此外,猪Lhx3与垂体转录因子Pit-1协同诱导催乳素增强子/启动子报告基因的转录。猪Lhx3蛋白在溶液中与Pit-1蛋白相互作用,也与LIM结构域结合蛋白NLI/Lbd1/CLIM相互作用。总之,这些数据表明Lhx3在哺乳动物垂体中的许多功能方面是保守的,并且Lhx3可能参与垂体器官发生早期和晚期滋养激素基因的激活。哺乳动物物种间Lhx3氨基酸序列的差异可能表明该蛋白在某些物种中具有不同的活性,并可能有助于确定这个关键发育转录因子的重要功能结构域。

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