Ale-Agha Niloofar, Dyballa-Rukes Nadine, Jakob Sascha, Altschmied Joachim, Haendeler Judith
IUF - Leibniz Research Institute for Environmental Medicine at the University of Duesseldorf gGmbH, 40225 Duesseldorf, Germany.
Central Institute of Clinical Chemistry and Laboratory Medicine, University of Duesseldorf, Germany; IUF - Leibniz Research Institute for Environmental Medicine at the University of Duesseldorf gGmbH, 40225 Duesseldorf, Germany.
Exp Gerontol. 2014 Aug;56:189-93. doi: 10.1016/j.exger.2014.02.011. Epub 2014 Feb 28.
Over the last 40 years it has become clear that telomeres, the end of the chromosomes, and the enzyme telomerase reverse transcriptase (TERT), which is required to counteract their shortening, play a pivotal role in senescence and aging. However, over the last years several studies demonstrated that TERT belongs to the group of dual-targeted proteins. It contains a bipartite nuclear localization signal as well as a mitochondrial targeting sequence and, under physiological conditions, is found in both organelles in several cell types including terminally differentiated, post-mitotic cells. The canonical function of TERT is to prevent telomere erosion and thereby the development of replicative senescence and genetic instability. Besides telomere extension, TERT exhibits other non-telomeric activities such as cell cycle regulation, modulation of cellular signaling and gene expression, augmentation of proliferative lifespan as well as DNA damage responses. Mitochondrial TERT is able to reduce reactive oxygen species, mitochondrial DNA damage and apoptosis. Because of the localization of TERT in the nucleus and in the mitochondria, it must have different functions in the two organelles as mitochondrial DNA does not contain telomeric structures. However, the organelle-specific functions are not completely understood. Strikingly, the regulation by phosphorylation of TERT seems to reveal multiple parallels. This review will summarize the current knowledge about the cellular functions and post-translational regulation of the dual-targeted protein TERT.
在过去40年里，很明显，端粒（染色体末端）以及为抵消其缩短所必需的端粒酶逆转录酶（TERT）在衰老过程中起着关键作用。然而，在过去几年里，多项研究表明TERT属于双靶向蛋白组。它含有一个双分核定位信号以及一个线粒体靶向序列，在生理条件下，在包括终末分化的有丝分裂后细胞在内的几种细胞类型的两种细胞器中都能找到。TERT的经典功能是防止端粒侵蚀，从而防止复制性衰老和遗传不稳定的发生。除了端粒延长外，TERT还表现出其他非端粒活性，如细胞周期调控、细胞信号传导和基因表达的调节、增殖寿命的延长以及DNA损伤反应。线粒体TERT能够减少活性氧、线粒体DNA损伤和细胞凋亡。由于TERT定位于细胞核和线粒体，由于线粒体DNA不包含端粒结构，它在这两种细胞器中必定具有不同的功能。然而，细胞器特异性功能尚未完全了解。引人注目的是，TERT的磷酸化调节似乎显示出多个相似之处。本综述将总结关于双靶向蛋白TERT的细胞功能和翻译后调节的当前知识。
