REGULATION OF MICROTUBULE DYNAMICS BY LIM KINASE1 (LIMK1)

LIM 激酶 1 (LIMK1) 对微管动力学的调节

• 批准号: nhmrc : 395517
• 负责人: Dr Ora Bernard
• 金额: $ 25.74万
• 依托单位: St. Vincent's Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/regulation-microtubule-dynamics-kinase1-limk1/97925
• 关键词: REGULATION; MICROTUBULE; DYNAMICS; LIM; KINASE1

Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. We have found that LIMK1 is very important in controlling the polymerisation of one of the most abundant molecules in the cell, actin. We have now preliminary data to show that LIMK1 also controls another important cellular protein, tubulin. Changes in tubulin polymerisation are of extreme importance for cell division and drugs affecting the state of tubulin are very potent as anti-cancer drugs. The goals of this research are: (1) To confirm that LIMK1 regulates the polymerisation of tubulin and (2) To demonstrate that LIMK1 regulates tubulin polymerisation by controlling the activity of p25, a protein involved in tubulin polymerisation that is modified by LIMK1. The results from this research will be highly significant because LIMK1 is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise. Therefore, we have to identify the other functions of LIMK1 to eliminate the possibility that drugs that inhibit LIMK1 and metastasis don't affect other organs and cells in the body. New molecules regulated by LIMK1 may also be suitable targets for drug development because through their inhibition we may also regulate other LIMK1 activities and possibly metastasis.

与局限性疾病不同，播散性癌症很少能通过药物治疗治愈。我们发现LIM激酶（LIMK1）是我们实验室发现的一种蛋白质，在控制肿瘤细胞扩散的能力中起着重要作用，这一过程称为转移。因此，这种蛋白质成为开发新药物疗法以防止癌症扩散的重要靶点。我们发现LIMK1在控制细胞中最丰富的分子之一肌动蛋白的聚合中非常重要。我们现在有初步的数据表明LIMK1还控制另一种重要的细胞蛋白质微管蛋白。微管蛋白聚合的变化对细胞分裂极其重要，影响微管蛋白状态的药物作为抗癌药物非常有效。本研究的目的是：（1）证实LIMK1调节微管蛋白的聚合和（2）证明LIMK1通过控制p25的活性来调节微管蛋白聚合，p25是一种参与微管蛋白聚合的蛋白质，由LIMK1修饰。这项研究的结果将是非常重要的，因为LIMK1是一个新的药物开发靶点。抑制这种蛋白质的药物可能会阻止肿瘤侵袭和转移的能力。因此，我们必须确定LIMK1的其他功能，以消除抑制LIMK1和转移的药物不影响体内其他器官和细胞的可能性。由LIMK1调节的新分子也可能是药物开发的合适靶点，因为通过它们的抑制，我们也可以调节其他LIMK1活性和可能的转移。