biostudies-literatureUnknown41(7)Jin YUpregulation of human telomerase reverse transcriptase (hTERT) expression is an important factor in the cellular survival and cancer. Although growing evidence suggests that hTERT inhibits cellular apoptosis by telomere-independent functions, the mechanisms involved are not fully understood. Here, we show that hTERT contains a BH3-like motif, a short peptide sequence found in BCL-2 family proteins, and interacts with anti-apoptotic BCL-2 family proteins MCL-1 and BCL-xL, suggesting a functional link between hTERT and the mitochondrial pathway of apoptosis. Additionally, we propose that hTERT can be categorized into the atypical BH3-only proteins that promote cellular survival, possibly due to the non-canonical interaction between hTERT and antiapoptotic proteins. Although the detailed mechMolecules and cells684-694https://www.ebi.ac.uk/biostudies/studies/S-EPMC6078858biostudies-literatureTelomerase Reverse Transcriptase Contains a BH3-Like Motif and Interacts with BCL-2 Family Members.PMC6078858You LKim HJJin YLee HWfalseTelomerase Reverse Transcriptase Contains a BH3-Like Motif and Interacts with BCL-2 Family Members.Upregulation of human telomerase reverse transcriptase (hTERT) expression is an important factor in the cellular survival and cancer. Although growing evidence suggests that hTERT inhibits cellular apoptosis by telomere-independent functions, the mechanisms involved are not fully understood. Here, we show that hTERT contains a BH3-like motif, a short peptide sequence found in BCL-2 family proteins, and interacts with anti-apoptotic BCL-2 family proteins MCL-1 and BCL-xL, suggesting a functional link between hTERT and the mitochondrial pathway of apoptosis. Additionally, we propose that hTERT can be categorized into the atypical BH3-only proteins that promote cellular survival, possibly due to the non-canonical interaction between hTERT and antiapoptotic proteins. Although the detailed mech2018-01-01T00:00:00Z2018 Jul2025-04-04T23:44:41.112Z2019-03-26T23:52:12ZS-EPMC60788582993747910.14348/molcells.2018.0206