Endoplasmic reticulum stress activates telomerase.

Telomerase contributes to cell proliferation and survival through both telomere-dependent and telomere-independent mechanisms. In this report, we discovered that endoplasmic reticulum (ER) stress transiently activates the catalytic components of telomerase (TERT) expression in human cancer cell lines and murine primary neural cells. Importantly, we show that depletion of hTERT sensitizes cells to undergo apoptosis under ER stress, whereas increased hTERT expression reduces ER stress-induced cell death independent of catalytically active enzyme or DNA damage signaling. Our findings establish a functional link between ER stress and telomerase, both of which have important implications in the pathologies associated with aging and cancer.

端粒酶通过端粒依赖和端粒非依赖机制促进细胞增殖和存活。在本报告中，我们发现内质网（ER）应激可瞬时激活人类癌细胞系和小鼠原代神经细胞中端粒酶催化成分（TERT）的表达。重要的是，我们表明hTERT的缺失使细胞在内质网应激下更易发生凋亡，而hTERT表达增加可减少内质网应激诱导的细胞死亡，且这种作用与具有催化活性的酶或DNA损伤信号无关。我们的研究结果建立了内质网应激和端粒酶之间的功能联系，这两者在与衰老和癌症相关的病理学中都具有重要意义。