title: Telomerase reverse transcriptase induces basal and amino acid starvation-induced autophagy through mTORC1.
abstract: Telomerase is a reverse transcriptase that consists of the telomerase RNA component (TERC) and the reverse transcriptase catalytic subunit (TERT) and specializes in the elongation of telomere ends. New evidence suggests that beyond classical telomere maintenance, TERT also possesses telomere length-independent functions that are executed via interaction with other binding proteins. One such reported TERT-interacting proteins is mTOR, a master nutrient sensor that is upregulated in several cancers; however, the physiological implications of the TERT-mTOR interaction in normal cellular processes as well as in tumorigenesis are poorly understood. Here, we report that TERT inhibits the kinase activity of mTOR complex 1 (mTORC1) in multiple cell lines, resulting in the activation of autophagy under both basal and amino acid-deprived conditions. Furthermore, TERT-deficient cells display the inability to properly execute the autophagy flux. Functionally, TERT-induced autophagy provides a survival advantage to cells in nutrient-deprived conditions. Collectively, these findings support a model in which gain of TERT function modulates mTORC1 activity and induces autophagy, which is required for metabolic rewiring to scavenge the nutrients necessary for fueling cancer cell growth in challenging tumor microenvironments.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Sushil
authors.initials: S
authors.lastname: Devkota
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Jae-Il
authors.initials: JI
authors.lastname: Roh
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea; Laboratory Animal Research Center, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: hwl@yonsei.ac.kr.
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000596:Amino Acids / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D019098:Telomerase
keywords: Autophagy; Cell viability; Human telomerase reverse transcriptase (hTERT); Mammalian target of rapamycin complex 1 (mTORC1); Telomerase