Pollok S, Bauerschmidt C, Sänger J, Nasheuer H-P, Grosse F
Leibniz Institute for Age Research, Fritz Lipmann Institute, Jena, Germany Radiation Oncology and Biology, University of Oxford, UK Institute of Pathology, Bad Berka, Germany National University of Ireland, Department of Biochemistry, Galway, Ireland Center for Molecular Biomedicine, Friedrich Schiller University, Jena, Germany.
FEBS J. 2007 Jul;274(14):3669-3684. doi: 10.1111/j.1742-4658.2007.05900.x. Epub 2007 Jul 3.
Cell division cycle protein 45 (Cdc45) plays a critical role in DNA replication to ensure that chromosomal DNA is replicated only once per cell cycle. We analysed the expression of human Cdc45 in proliferating and nonproliferating cells. Our findings show that Cdc45 protein is absent from long-term quiescent, terminally differentiated and senescent human cells, although it is present throughout the cell cycle of proliferating cells. Moreover, Cdc45 is much less abundant than the minichromosome maintenance (Mcm) proteins in human cells, supporting the concept that origin binding of Cdc45 is rate limiting for replication initiation. We also show that the Cdc45 protein level is consistently higher in human cancer-derived cells compared with primary human cells. Consequently, tumour tissue is preferentially stained using Cdc45-specific antibodies. Thus, Cdc45 expression is tightly associated with proliferating cell populations and Cdc45 seems to be a promising candidate for a novel proliferation marker in cancer cell biology.
细胞分裂周期蛋白45（Cdc45）在DNA复制过程中起着关键作用，以确保染色体DNA在每个细胞周期中仅复制一次。我们分析了人类Cdc45在增殖细胞和非增殖细胞中的表达情况。我们的研究结果表明，长期静止、终末分化和衰老的人类细胞中不存在Cdc45蛋白，尽管它在增殖细胞的整个细胞周期中都存在。此外，在人类细胞中，Cdc45的丰度远低于微小染色体维持（Mcm）蛋白，这支持了Cdc45与起始点的结合对复制起始起限速作用这一观点。我们还表明，与原代人类细胞相比，人类癌症衍生细胞中的Cdc45蛋白水平始终较高。因此，使用Cdc45特异性抗体对肿瘤组织进行优先染色。因此，Cdc45的表达与增殖细胞群体密切相关，并且Cdc45似乎是癌细胞生物学中一种新型增殖标志物的有希望的候选者。
