Irminger-Finger Irmgard, Ratajska Magda, Pilyugin Maxim
Molecular Gynecology and Obstetrics Laboratory, Department of Gynecology and Obstetrics and Department of Medical Genetics and Laboratories, University Hospitals Geneva, Geneva, Switzerland; Centre for Cell Therapy and Regenerative Medicine, University of Western Australia, Nedlands, WA, Australia.
Centre for Cell Therapy and Regenerative Medicine, University of Western Australia, Nedlands, WA, Australia; Department of Gynecology and Obstetrics, Medical University of Gdansk, Gdansk, Poland.
Int J Biochem Cell Biol. 2016 Mar;72:1-17. doi: 10.1016/j.biocel.2015.12.008. Epub 2015 Dec 29.
For nearly two decades most research on BARD1 was closely linked to research on BRCA1, the breast cancer predisposition gene. The co-expression of BARD1 and BRCA1 genes in most tissues, the nearly identical phenotype of Bard1 and Brca1 knock-out mice, and the fact that BRCA1 and BARD1 proteins form a stable complex, led to the general assumption that BARD1 acts as an accessory to BRCA1. More recent research on both proteins showed that BRCA1 and BARD1 might have common as well as separate functions. This review is an overview of how BARD1 functions and controls BRCA1. It highlights also experimental evidence for dominant negative, tumor promoting, functions of aberrant isoforms of BARD1 that are associated with and drivers of various types of cancer.
在近二十年里，大多数关于BARD1的研究都与乳腺癌易感基因BRCA1的研究紧密相关。BARD1和BRCA1基因在大多数组织中的共表达、Bard1和Brca1基因敲除小鼠几乎相同的表型，以及BRCA1和BARD1蛋白形成稳定复合物这一事实，使得人们普遍认为BARD1是BRCA1的辅助因子。最近对这两种蛋白的研究表明，BRCA1和BARD1可能既有共同功能，也有各自独立的功能。这篇综述概述了BARD1如何发挥功能并调控BRCA1。它还强调了一些实验证据，这些证据表明BARD1异常异构体具有显性负性、促肿瘤功能，与各种类型癌症的发生相关并起着驱动作用。
