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.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2016|
Bibliographical noteFunding Information:
This research was supported by a grant ( 14182MFDS978 ) from Korea Food and Drug Administration in 2016, the National Research Foundation of Korea (NRF) grants funded by the Ministry of Education, Science and Technology (MEST) of the Korean government ( 2010-0020878 , 2015R1A2A1A01003845 ); a Korea Healthcare Technology R&D Project from the Ministry of Health & Welfare Affairs ( A085136 ). The Yonsei University , Yonsei-SNU collaborative research fund of 2014 also provided funding for this study. M.A. was also supported by the Higher Education Commission (HEC) of the Pakistan government .
© 2016 The Author(s)
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology