Chen Fabian, Kook Hyun, Milewski Rita, Gitler Aaron D, Lu Min Min, Li Jun, Nazarian Ronniel, Schnepp Robert, Jen Kuangyu, Biben Christine, Runke Greg, Mackay Joel P, Novotny Jiri, Schwartz Robert J, Harvey Richard P, Mullins Mary C, Epstein Jonathan A
Department of Medicine, University of Pennsylvania Health System, Philadelphia, PA 19104, USA.
Cell. 2002 Sep 20;110(6):713-23. doi: 10.1016/s0092-8674(02)00932-7.
Hop is a small, divergent homeodomain protein that lacks certain conserved residues required for DNA binding. Hop gene expression initiates early in cardiogenesis and continues in cardiomyocytes throughout embryonic and postnatal development. Genetic and biochemical data indicate that Hop functions directly downstream of Nkx2-5. Inactivation of Hop in mice by homologous recombination results in a partially penetrant embryonic lethal phenotype with severe developmental cardiac defects involving the myocardium. Inhibition of Hop activity in zebrafish embryos likewise disrupts cardiac development and results in severely impaired cardiac function. Hop physically interacts with serum response factor (SRF) and inhibits activation of SRF-dependent transcription by inhibiting SRF binding to DNA. Hop encodes an unusual homeodomain protein that modulates SRF-dependent cardiac-specific gene expression and cardiac development.
Hop是一种小型的、具有差异的同源异型结构域蛋白，它缺乏DNA结合所需的某些保守残基。Hop基因表达在心脏发生早期启动，并在整个胚胎和出生后发育过程中在心肌细胞中持续存在。遗传和生化数据表明，Hop在Nkx2-5的直接下游发挥作用。通过同源重组使小鼠体内的Hop失活会导致部分胚胎致死表型，伴有涉及心肌的严重发育性心脏缺陷。抑制斑马鱼胚胎中的Hop活性同样会破坏心脏发育并导致心脏功能严重受损。Hop与血清反应因子（SRF）发生物理相互作用，并通过抑制SRF与DNA的结合来抑制SRF依赖性转录的激活。Hop编码一种不寻常的同源异型结构域蛋白，该蛋白调节SRF依赖性心脏特异性基因表达和心脏发育。
