Functional analysis of the p160 Myb-binding protein - a regulator of multiple transcription factors?

p160 Myb 结合蛋白的功能分析 - 多种转录因子的调节因子？

• 批准号: nhmrc : 104878
• 负责人: Prof Thomas Gonda
• 金额: $ 25.12万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/functional-analysis-p160-transcription-factors/98824
• 关键词: Functional; analysis; p160; Myb; binding

The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is likely to be responsible for regulating Myb. However, it has recently become apparent that p160 interacts with a number of other transcription factors in addition Myb. The primary aim of this project is to elucidate precisely how p160 interacts with Myb and what the consequences of this interaction are. A range of experimental approaches, which range from in vitro to genetic studies, will be employed to do this. We will test a specific role of p160 suggested by our preliminary studies - that of a transporter of transcription factors between the nucleus and the cytoplasm of the cell. Because of the wide range of transcription factors that p160 interacts with, its effects on the function of the cell are likely to be profound. For this same reason, it is difficult to specifically predict the possible medical-health implications of this work However, what we know to date is consistent with a role for p160 as a tumour suppressor gene. Moreover, parts of this project aim to generate genetic information and tools which will help in determining whether p160 does play such a role and generally, in identifying any other associations of p160 with particular diseases.

c-myb基因是正常血细胞生成的关键分子调节因子，但该基因的改变也会导致白血病。由c-myb基因编码的蛋白质（Myb）作为转录因子，即控制其他基因的活性。有充分的证据表明，与其他蛋白质的相互作用可以调节Myb的活性。我们的实验室已经确定了一种我们认为是这样的蛋白质p160，它与Myb的一部分结合，降低了它的活性，因此它可能负责调节Myb。然而，最近发现p160与Myb之外的许多其他转录因子相互作用。该项目的主要目的是精确地阐明p160如何与Myb相互作用以及这种相互作用的后果。将采用从体外到基因研究的一系列实验方法来实现这一目标。我们将测试p160在我们的初步研究中提出的一种特殊作用——在细胞核和细胞质之间作为转录因子的转运体。由于p160与多种转录因子相互作用，其对细胞功能的影响可能是深远的。出于同样的原因，很难具体预测这项工作可能的医学健康意义。然而，我们迄今所知道的是p160作为肿瘤抑制基因的作用是一致的。此外，该项目的部分目的是产生遗传信息和工具，这些信息和工具将有助于确定p160是否确实发挥这种作用，并在一般情况下确定p160与特定疾病的任何其他关联。