Study gene regulation of telomerase by transcription factor KLF4 in stem cells

• Main Authors: Chui-Wei Wong, 黃翠薇
• Other Authors: Shu-Chun Teng
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/01366240947350365009

博士 === 國立臺灣大學 === 微生物學研究所 === 98 === The zinc finger Kruppel-like transcription factor 4 (KLF4) has been implicated in cancer formation and stem cell regulation. However, the function of KLF4 in tumorigenesis and stem cell regulation are poorly understood due to limited knowledge of its targets in these cells. In this study, we have revealed a surprising link between KLF4 and regulation of telomerase, which offers important insight into how KLF4 contributes to cancer formation and stem cell regulation. KLF4 sufficiently activated expression of the human telomerase catalytic subunit, hTERT, in telomerase-low ALT and fibroblast cells, while down-regulation of KLF4 reduced its expression in cancerous and stem cells which normally exhibits high expression. Furthermore, KLF4-dependent induction of hTERT was mediated by a KLF4 binding site in the proximal promoter region of hTERT. In human embryonic stem cells, expression of hTERT replaced KLF4 function to maintain their self-renewal. Therefore, our findings demonstrate that hTERT is one of the major targets of KLF4 in cancer and stem cells to maintain long-term proliferation potential.