Publication Date:
2012-06-23
Description:
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(DeltaEx3/+)) 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hoffmeyer, Katrin -- Raggioli, Angelo -- Rudloff, Stefan -- Anton, Roman -- Hierholzer, Andreas -- Del Valle, Ignacio -- Hein, Kerstin -- Vogt, Riana -- Kemler, Rolf -- New York, N.Y. -- Science. 2012 Jun 22;336(6088):1549-54. doi: 10.1126/science.1218370.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22723415" target="_blank"〉PubMed〈/a〉
Keywords:
Adult Stem Cells/*metabolism
;
Animals
;
Cell Line, Tumor
;
Embryonic Stem Cells/*metabolism
;
HEK293 Cells
;
Humans
;
Kruppel-Like Transcription Factors/metabolism
;
Mice
;
Neoplasms/genetics/*metabolism
;
Promoter Regions, Genetic
;
RNA, Messenger/genetics/metabolism
;
Telomerase/*genetics/metabolism
;
Telomere/metabolism/ultrastructure
;
Telomere Homeostasis
;
Transcription Initiation Site
;
Wnt Proteins/metabolism
;
*Wnt Signaling Pathway
;
beta Catenin/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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