Journal
SCIENCE
Volume 336, Issue 6088, Pages 1549-1554Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1218370
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- Max Planck Society
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Telomerase activity controls telomere length and plays a pivotal role in stem cells, aging, and cancer. Here, we report a molecular link between Wnt/beta-catenin signaling and the expression of the telomerase subunit Tert. beta-Catenin-deficient mouse embryonic stem (ES) cells have short telomeres; conversely, ES cell expressing an activated form of beta-catenin (beta-cat(Delta Ex3/+)) have long telomeres. We show that beta-catenin regulates Tert expression through the interaction with Klf4, a core component of the pluripotency transcriptional network. beta-Catenin binds to the Tert promoter in a mouse intestinal tumor model and in human carcinoma cells. We uncover a previously unknown link between the stem cell and oncogenic potential whereby beta-catenin regulates Tert expression, and thereby telomere length, which could be critical in human regenerative therapy and cancer.
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