Human telomerase reverse transcriptase immortalizes bovine lens epithelial cells and suppresses differentiation through regulation of the ERK signaling pathway

Juan Wang, Hao Feng, Xiao Qin Huang, Hua Xiang, Ying Wei Mao, Jin Ping Liu, Qin Yan, Wen Bin Liu, Yan Liu, Mi Deng, Lili Gong, Shuming Sun, Chen Luo, Shao Jun Liu, Xuan Jie Zhang, Yun Liu, David Wan Cheng Li

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Abstract

Telomerase is a specialized reverse transcriptase that extends telomeres of eukaryotic chromosomes. The functional telomerase complex contains a telomerase reverse transcriptase catalytic subunit and a telomerase template RNA. We have previously demonstrated that human telomerase reverse transcriptase (hTERT) catalytic subunit is functionally compatible with a telomerase template RNA from rabbit. In this study, we show that hTERT is also functionally compatible with a telomerase template RNA from bovine. Introduction of hTERT into bovine lens epithelial cells (BLECs) provides the transfected cells telomerase activity. The expressed hTERT in BLECs supports normal growth of the transfected cells for 108 population doublings so far, and these cells are still extremely healthy in both morphology and growth. In contrast, the vector-transfected cells display growth crisis after 20 population doublings. These cells run into cellular senescence due to shortening of the telomeres and also commit differentiation as indicated by the accumulation of the differentiation markers, β-crystallin and filensin. hTERT prevents the occurrence of both events. By synthesizing new telomere, hTERT prevents replicative senescence, and through regulation of MEK/ERK, protein kinase C, and protein kinase A and eventual suppression of the MEK/ERK signaling pathway, hTERT inhibits differentiation of BLECs. Our finding that hTERT can suppress RAS/RAF/MEK/ERK signaling pathway to prevent differentiation provides a novel mechanism to explain how hTERT regulates cell differentiation.

Original languageEnglish (US)
Pages (from-to)22776-22787
Number of pages12
JournalJournal of Biological Chemistry
Volume280
Issue number24
DOIs
StatePublished - Jun 17 2005

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wang, J., Feng, H., Huang, X. Q., Xiang, H., Mao, Y. W., Liu, J. P., Yan, Q., Liu, W. B., Liu, Y., Deng, M., Gong, L., Sun, S., Luo, C., Liu, S. J., Zhang, X. J., Liu, Y., & Li, D. W. C. (2005). Human telomerase reverse transcriptase immortalizes bovine lens epithelial cells and suppresses differentiation through regulation of the ERK signaling pathway. Journal of Biological Chemistry, 280(24), 22776-22787. https://doi.org/10.1074/jbc.M500032200