title: Cellular functions of the dual-targeted catalytic subunit of telomerase, telomerase reverse transcriptase--potential role in senescence and aging.
abstract: 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.
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine at the University of Duesseldorf gGmbH, 40225 Duesseldorf, Germany. Electronic address: Niloofar.Ale-Agha@uni-duesseldorf.de.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Ale-Agha
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine at the University of Duesseldorf gGmbH, 40225 Duesseldorf, Germany. Electronic address: Nadine.Dyballa@uni-duesseldorf.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Dyballa-Rukes
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine at the University of Duesseldorf gGmbH, 40225 Duesseldorf, Germany. Electronic address: Sascha.Jakob@uni-duesseldorf.de.
authors.forename: Sascha
authors.initials: S
authors.lastname: Jakob
authors.affiliation: IUF - Leibniz Research Institute for Environmental Medicine at the University of Duesseldorf gGmbH, 40225 Duesseldorf, Germany. Electronic address: Joachim.Altschmied@uni-duesseldorf.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Altschmied
authors.affiliation: 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. Electronic address: juhae001@uni-duesseldorf.de.
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
mesh_terms: D021581:Active Transport, Cell Nucleus; D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020134:Catalytic Domain; D016922:Cellular Senescence; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D010766:Phosphorylation; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: Aging; Mitochondria; Nucleus; Senescence; Telomerase reverse transcriptase