Irminger-Finger Irmgard, Leung Wai Choi
Louis Jeantet Laboratory of Aging Research, Department of Geriatrics, University of Geneva, Geneva, Switzerland.
Int J Biochem Cell Biol. 2002 Jun;34(6):582-7. doi: 10.1016/s1357-2725(01)00161-3.
Breast cancer susceptibility gene 1 (BRCA1)-associated RING domain (BARD1) was discovered as a protein interacting with the RING domain of BRCA1. It is structurally homologous to BRCA1 with which it shares the conserved RING finger and BRCT domains. BARD1 is strongly expressed in spleen and testis, correlated with the expression of BRCA1. Co-localization of BARD1 with BRCA1 and other repair proteins indicate a function in DNA repair. A potential role of BARD1-BRCA1 complexes in ubiquitination of RNA Pol II, and the interaction of BARD1 with polyadenylation factor CstF-50, thus inhibiting mRNA processing, provide mechanisms for tumor suppression. BRCA1-independent functions of BARD1 were first noted by its inordinate expression in hormonally regulated uterine tissue. BARD1 repression lead to a premalignant phenotype in mammary gland epithelial cells. The interaction of BARD1 with NF-kappaB, suggests modulation of transcriptional activity independent of BRCA1. Elevated BARD1 expression in apoptotic tumor cells was found associated with anti-BARD1 immune response thus leading to new therapeutic approaches.
乳腺癌易感基因1（BRCA1）相关的RING结构域（BARD1）最初被发现是一种与BRCA1的RING结构域相互作用的蛋白质。它在结构上与BRCA1同源，二者共享保守的RING指结构域和BRCT结构域。BARD1在脾脏和睾丸中强烈表达，与BRCA1的表达相关。BARD1与BRCA1及其他修复蛋白的共定位表明其在DNA修复中发挥作用。BARD1-BRCA1复合物在RNA聚合酶II泛素化中的潜在作用，以及BARD1与聚腺苷酸化因子CstF-50的相互作用从而抑制mRNA加工，为肿瘤抑制提供了机制。BARD1不依赖BRCA1的功能最初是通过其在激素调节的子宫组织中的过度表达而被注意到的。BARD1的抑制导致乳腺上皮细胞出现癌前表型。BARD1与核因子κB的相互作用表明其对转录活性的调节独立于BRCA1。在凋亡肿瘤细胞中发现BARD1表达升高与抗BARD1免疫反应相关，从而带来了新的治疗方法。
