Telomerase reverse transcriptase regulates the expression of a key cell cycle regulator, cyclin D1.
Cells require a mechanism to maintain telomere stability in order to overcome replicative senescence and telomerase catalyzes the synthesis and extension of telomeric DNA, therefore, be a rate-limiting step in cellular immortality and oncogenesis. However, some studies have raised questions about whether the stabilization of chromosome ends entirely explains the ability of telomerase to promote tumorigenesis. To elucidate non-canonical functions of human telomerase reverse transcriptase (hTERT), we used loss-of-function and gain-of-function studies. We demonstrated that hTERT shRNA down-regulated and hTERT overexpression up-regulated the expression and transcriptional activity of a key cell cycle regulator, cyclin D1, in human prostate epithelial cell lines, DU-145 and BPH-1. Based on these observations, we propose that in addition to its well-defined function in telomere length regulation, hTERT has a novel role in the modulation of cyclin D1 expression.
Jagadeesh
Shankar
S
Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA.
Banerjee
Partha P
PP
D021581:Active Transport, Cell Nucleus; D002453:Cell Cycle; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D019938:Cyclin D1; D019098:Telomerase