Dahmcke Christina Mackeprang, Büchmann-Møller Stine, Jensen Niels A, Mitchelmore Cathy
Eucaryotic Cell Biology Research Group, Department of Science, Roskilde University, Roskilde, Denmark.
Mol Cell Neurosci. 2008 Aug;38(4):589-94. doi: 10.1016/j.mcn.2008.05.007. Epub 2008 May 20.
In order to understand the gene-mediated processes underlying sporadic Alzheimer's disease (AD), we carried out a subtractive cloning screen for novel AD candidate genes. We identified the gene encoding the DNA replication factor CIZ1 (CDKN1A interacting zinc finger protein 1) as being more highly expressed in Alzheimer tissue than in healthy brains. We show here that an isoform of CIZ1 which lacks a glutamine-rich region, due to alternative splicing in exon 8, is upregulated in AD brains relative to the full-length CIZ1 protein. We demonstrate for the first time that a minimal 28 amino acid sequence within this region is required for CIZ1 to associate with the nuclear matrix and to form nuclear foci.
为了了解散发性阿尔茨海默病（AD）潜在的基因介导过程，我们对新的AD候选基因进行了消减克隆筛选。我们鉴定出编码DNA复制因子CIZ1（细胞周期蛋白依赖性激酶1A相互作用锌指蛋白1）的基因在阿尔茨海默病组织中的表达高于健康大脑。我们在此表明，由于外显子8中的可变剪接，缺乏富含谷氨酰胺区域的CIZ1同工型在AD大脑中相对于全长CIZ1蛋白上调。我们首次证明该区域内最小的28个氨基酸序列是CIZ1与核基质结合并形成核灶所必需的。
