Negative regulation of selected bHLH proteins by eHAND
Negative regulation of selected bHLH proteins by eHAND
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DOI：
10.1006/excr.2000.4898
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发表时间：
2000-06-15
影响因子：
3.7
通讯作者：
Christy, BA
中科院分区：
文献类型：
--
作者：
Bounpheng, MA;Morrish, TA;Christy, BA
bHLH蛋白eHAND在胚外、中胚层和心脏细胞谱系的发育中起重要作用，推测是通过与其他HLH蛋白的异二聚化和DNA结合。在这项研究中，我们已经确定了一个新的转录活性的eHAND。在瞬时转染试验中，eHAND是一些但不是所有bHLH蛋白激活的有效抑制剂，eHAND可以阻止这些bHLH蛋白与E-box DNA结合。有趣的是，eHAND也可以强烈抑制MyoD的反式激活活性，类似于E47栓系二聚体，这表明了不同的作用机制。eHAND还抑制MyoD依赖性骨骼肌细胞分化和肌肉特异性肌球蛋白重链蛋白的表达。此外，我们表明，eHAND可以抑制活性的天然p75 LNGFR启动子，其表达重叠的eHAND和dHAND。eHAND的抑制活性可能归因于多种机制，例如作为辅阻遏物的能力、阻遏结构域的存在以及其在无活性复合物中螯合E蛋白的能力。基于其对bHLH蛋白和细胞分化的抑制作用，我们提出eHAND可能通过几种机制来负调节bHLH蛋白MASH-2的活性，从而促进胎盘巨细胞增殖。(C)北京大学出版社.
The bHLH protein eHAND plays an important role in the development of extraembryonic, mesodermal, and cardiac cell lineages, presumably through heterodimerization with other HLH proteins and DNA binding. In this study, we have identified a novel transcriptional activity of eHAND. In transient transfection assays, eHAND is a potent inhibitor of activation by some but not all bHLH proteins, eHAND can prevent E-box DNA binding by these bHLH proteins. Interestingly, eHAND can also strongly inhibit transactivation activity by a MyoD similar to E47 tethered dimer, which suggests a distinct mechanism of action. eHAND also inhibits MyoD-dependent skeletal muscle cell differentiation and expression of the muscle-specific myosin heavy chain protein. In addition, we show that eHAND can repress activity of the natural p75LNGFR promoter, whose expression overlaps that of eHAND and dHAND. The inhibitory activity of eHAND may be attributed to multiple mechanisms, such as the ability to act as a corepressor, the presence of a repression domain, and its ability to sequester E proteins in an inactive complex. Based upon its inhibitory effect on bHLH proteins and cellular differentiation, we propose that eHAND may function by several mechanisms to promote placental giant cell proliferation by negatively regulating the activities of the bHLH protein MASH-2. (C) 2000 Academic Press.