Role of the Growth Hormone Binding Protein as a Transcriptional Activator

生长激素结合蛋白作为转录激活剂的作用

• 批准号: nhmrc : 142960
• 负责人: Prof Michael Waters
• 金额: $ 25.82万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-growth-hormone-transcriptional-activator/77452
• 关键词: Role; Growth; Hormone; Binding; Protein

Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This proposal examines a novel way that GH could work, that is by sending the extracellular part of its receptor (GHBP) to the nucleus, where it can directly activate gene readout. This would have the effect of augmenting the normal action of GH to regulate gene readout. We have exciting preliminary data which makes us think this may be a new mechanism for hormone activation of genes. The level of GHBP in the nucleus is regulated, and if a defect in export of the GHBP occurred, this would lead to accumulation of nuclear GHBP and stimulate cell proliferation. This may be important in cancer cell proliferation, since we find nuclear GHBP in cancers.

生长激素是治疗侏儒症的重要激素治疗药物。最近，已经发现了生长激素的许多新的治疗应用，特别是关于其作为合成代谢剂的作用。这些包括术后恢复，增强骨折愈合，克罗恩病，扩张型心肌病，不孕症，当然还有衰老。该提案研究了GH可以工作的一种新方式，即通过将其受体的细胞外部分（GHBP）发送到细胞核，在那里它可以直接激活基因读出。这将具有增强GH调节基因读出的正常作用的效果。我们有令人兴奋的初步数据，使我们认为这可能是激素激活基因的新机制。GHBP在细胞核中的水平是受调节的，如果GHBP的输出发生缺陷，这将导致细胞核GHBP的积累并刺激细胞增殖。这在癌细胞增殖中可能是重要的，因为我们在癌症中发现了核GHBP。