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Hop2 Interacts with ATF4 to Promote Osteoblast Differentiation.
Journal of Bone and Mineral Research ( IF 5.1 ) Pub Date : 2019-11-04 , DOI: 10.1002/jbmr.3857
Yang Zhang 1, 2 , Tonghui Lin 1 , Na Lian 1 , Huan Tao 3 , Cong Li 1 , Lingzhen Li 4 , Xiangli Yang 1
Affiliation  

Activating transcription factor 4 (ATF4) is a member of the basic leucine zipper (bZip) transcription factor family required for the terminal differentiation of osteoblasts. Despite its critical importance as one of the three main osteoblast differentiation transcription factors, regulators of osteoblast terminal maturation remain poorly defined. Here we report the identification of homologous pairing protein 2 (Hop2) as a dimerization partner of ATF4 in osteoblasts via the yeast two-hybrid system. Deletional mapping revealed that the Zip domain of Hop2 is necessary and sufficient to bind ATF4 and to enhance ATF4-dependent transcription. Ectopic Hop2 expression in preosteoblasts increased endogenous ATF4 protein content and accelerated osteoblast differentiation. Mice lacking Hop2 (Hop2-/- ) have a normal stature but exhibit an osteopenic phenotype similar to the one observed in Atf4-/- mice, albeit milder, which is associated with decreased Osteocalcin mRNA expression and reduced type I collagen synthesis. Compound heterozygous mice (Atf4+/- :Hop2+/- ) display identical skeletal defects to those found in Hop2-/- mice. These results indicate that Hop2 plays a previous unknown role as a determinant of osteoblast maturation via its regulation of ATF4 transcriptional activity. Our work for the first time reveals a function of Hop2 beyond its role in guiding the alignment of homologous chromosomes. © 2019 American Society for Bone and Mineral Research.

中文翻译:

Hop2与ATF4相互作用以促进成骨细胞分化。

激活转录因子4(ATF4)是成骨细胞终末分化所需的基本亮氨酸拉链(bZip)转录因子家族的成员。尽管作为三个主要的成骨细胞分化转录因子之一至关重要,但成骨细胞末端成熟的调控因子仍然定义不清。在这里,我们报告通过酵母双杂交系统鉴定成骨细胞中ATF4的二聚体作为同源配对蛋白2(Hop2)。理想的作图表明,Hop2的Zip结构域对于结合ATF4和增强ATF4依赖性转录是必要和充分的。前成骨细胞中异位Hop2表达增加内源性ATF4蛋白含量并加速成骨细胞分化。缺乏Hop2(Hop2-/-)的小鼠具有正常的身材,但表现出与Atf4-/-小鼠相似的骨质疏松表型,尽管较轻,这与骨钙蛋白mRNA表达降低和I型胶原合成减少有关。复合杂合小鼠(Atf4 +/-:Hop2 +/-)显示出与Hop2-/-小鼠相同的骨骼缺陷。这些结果表明,Hop2通过调节ATF4转录活性,在成骨细胞成熟中起着以前未知的作用。我们的工作首次揭示了Hop2在指导同源染色体比对中的功能。©2019美国骨骼和矿物质研究学会。这与减少骨钙素mRNA的表达和减少I型胶原蛋白的合成有关。复合杂合小鼠(Atf4 +/-:Hop2 +/-)显示出与Hop2-/-小鼠相同的骨骼缺陷。这些结果表明,Hop2通过调节ATF4转录活性,在成骨细胞成熟中起着以前未知的作用。我们的工作首次揭示了Hop2在指导同源染色体比对中的功能。©2019美国骨骼和矿物质研究学会。这与减少骨钙素mRNA的表达和减少I型胶原蛋白的合成有关。复合杂合小鼠(Atf4 +/-:Hop2 +/-)显示出与Hop2-/-小鼠相同的骨骼缺陷。这些结果表明,Hop2通过调节ATF4转录活性,在成骨细胞成熟中起着以前未知的作用。我们的工作首次揭示了Hop2在指导同源染色体比对中的功能。©2019美国骨骼和矿物质研究学会。我们的工作首次揭示了Hop2在指导同源染色体比对中的功能。©2019美国骨骼和矿物质研究学会。我们的工作首次揭示了Hop2在指导同源染色体比对中的功能。©2019美国骨骼和矿物质研究学会。
更新日期:2019-11-04
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