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Jae-il Roh

Jae-il Roh

Yonsei University, South Korea

Title: Hexokinase 2 is a molecular bridge linking telomerase and autophagy

Biography

Jae-il Roh has completed his PhD from Yonsei University and continuing his research at the same laboratory. He is working in Prof. Han-Woong Lee’s lab and
interested in mouse genetics, generation of mouse models, and cancer.

Abstract

Autophagy is systematically regulated by upstream factors and nutrients. Recent studies report that telomerase and hexokinase 2 (HK2) regulate autophagy through mTOR and that telomerase has the capacity to bind to the HK2 promoter. Here, we show that HK2 is a molecular bridge linking telomerase to autophagy. TERT-induced autophagy activation and its further enhancement by glucose deprivation were suppressed by HK2 inhibition in HepG2 cells. The HK2 downstream factor mTOR was responsible for TERT-induced autophagy activation under glucose deprivation, implying that TERT promotes autophagy through a HK2-mTOR pathway. TERC played a similar role as TERT, and simultaneous expression of TERT and TERC synergistically enhanced HK2 expression and autophagy. At the gene level, TERT bound to the HK2 promoter at a specific region harboring the telomerase-responsive sequence TTGGG. Mutagenesis of TERC and the TERT-responsive element on the HK2 promoter revealed that TERC is required for the binding of TERT to the HK2 promoter. We demonstrate the existence of a telomerase-HK2-mTOR-autophagy axis and suggest that inhibition of the interaction between telomerase and the HK2 promoter sensitizes cells to metabolic stress, and this pathway could be targeted for anti-cancer therapies.