Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 478 (3), 1198-204

Telomerase Reverse Transcriptase Induces Basal and Amino Acid Starvation-Induced Autophagy Through mTORC1

Affiliations

Telomerase Reverse Transcriptase Induces Basal and Amino Acid Starvation-Induced Autophagy Through mTORC1

Muhammad Ali et al. Biochem Biophys Res Commun.

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.

Keywords: Autophagy; Cell viability; Human telomerase reverse transcriptase (hTERT); Mammalian target of rapamycin complex 1 (mTORC1); Telomerase.

Similar articles

See all similar articles

Cited by 5 PubMed Central articles

Publication types

LinkOut - more resources

Feedback