Spanish National Cancer Centre, Madrid, Spain.
Aging Cell. 2010 Oct;9(5):653-66. doi: 10.1111/j.1474-9726.2010.00596.x. Epub 2010 Jul 22.
Mammalian telomeres are formed by tandem repeats of the TTAGGG sequence bound by a specialized six-protein complex known as shelterin, which has fundamental roles in the regulation of telomere length and telomere capping. In the past, the study of mice genetically modified for telomerase components has been instrumental to demonstrate the role of telomere length in cancer and aging. Recent studies using genetically modified mice for shelterin proteins have highlighted an equally important role of telomere-bound proteins in cancer and aging, even in the presence of proficient telomerase activity and normal telomere length. In this review, we will focus on recent findings, suggesting a role of shelterin components in cancer and aging.
哺乳动物端粒由 TTAGGG 序列的串联重复组成,由一种称为 shelterin 的特殊六蛋白复合物结合,该复合物在调节端粒长度和端粒封端方面具有重要作用。过去,对端粒酶成分进行基因修饰的小鼠的研究有助于证明端粒长度在癌症和衰老中的作用。最近使用基因修饰小鼠研究 shelterin 蛋白的研究突出了端粒结合蛋白在癌症和衰老中的同样重要作用,即使在端粒酶活性正常和端粒长度正常的情况下也是如此。在这篇综述中,我们将重点介绍最近的发现,这些发现表明 shelterin 成分在癌症和衰老中发挥作用。