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

C-myb基因是正常血细胞产生的关键分子调节器，但该基因的改变也可能导致白血病。C-myb基因编码的蛋白(Myb)起转录因子的作用，即控制其他基因的活性。有很好的证据表明，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，从而降低了它的活性，因此很可能负责调节Myb。然而，最近发现p160除了与Myb相互作用外，还与许多其他转录因子相互作用。这个项目的主要目的是确切地阐明p160是如何与Myb相互作用的，以及这种相互作用的后果是什么。从体外到基因研究的一系列实验方法将被用来做这项工作。我们将测试我们的初步研究提出的p160的一个特殊作用--在细胞核和细胞质之间运送转录因子的作用。由于p160与广泛的转录因子相互作用，它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带来的医疗健康影响，然而，我们迄今所知的与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生成遗传信息和工具，这些信息和工具将有助于确定p160是否确实发挥了这种作用，并通常有助于确定p160与特定疾病的任何其他联系。

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.