Regulation of the tumour suppressors APC and BRCA1 by nuclear export

通过核输出调节肿瘤抑制因子 APC 和 BRCA1

• 批准号: nhmrc : 107350
• 负责人: A/Pr Beric Henderson
• 金额: $ 35.4万
• 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/regulation-tumour-suppressors-nuclear-export/99779
• 关键词: Regulation; tumour; suppressors; APC; BRCA1

Cancer cells lack the ability to control their own growth, and thus continously divide in their local environment, leading to tumour formation. Tumour suppressor proteins, like APC and BRCA1, normally function as regulators to help cells respond to outside signals and to stop growing when necessary. The inactivation and altered cellular localisation of tumour suppressor proteins can contribute to cancer development. We have found that the APC and BRCA1 proteins, whose inactivation leads to development of colon cancer and breast cancer, respectively, contain signals that dictate their movement within the cell. Our novel preliminary findings reveal that APC and BRCA1 are able to move in and out of the cell nucleus. We aim to define how this occurs, and examine how the regulation of their cellular location affects the normal function of these cancer-suppressing proteins. Finally, abnormalities in the nuclear passage of APC or BRCA1 might explain their altered cellular location in cancer cells.

癌细胞缺乏控制自身生长的能力，因此在局部环境中不断分裂，导致肿瘤形成。肿瘤抑制蛋白，如APC和BRCA1，通常起调节作用，帮助细胞对外界信号作出反应，并在必要时停止生长。肿瘤抑制蛋白的失活和细胞定位的改变可以促进癌症的发展。我们发现APC和BRCA1蛋白的失活分别导致结肠癌和乳腺癌的发展，它们包含指示它们在细胞内运动的信号。我们新的初步研究结果表明，APC和BRCA1能够进出细胞核。我们的目标是确定这是如何发生的，并检查它们的细胞位置的调节如何影响这些癌症抑制蛋白的正常功能。最后，APC或BRCA1的核传代异常可能解释了它们在癌细胞中细胞位置的改变。