Human chromosome 5 carries a transcriptional regulator of human telomerase reverse transcriptase (hTERT)

Biochemical and Biophysical Research Communications
Dong-Lai QiH Kugoh

Abstract

Telomerase activation is crucial for cells that tend to be immortalized. Increased telomerase activity is correlated with upregulation of telomerase reverse transcriptase (TERT) expression. In most human somatic cells, hTERT expression is suppressed by multiple factors. We have previously shown that human chromosome 5 carries a possible suppressor of mouse tert mtert expression in a mouse melanoma cell line, B16-F10 cells. However, the function of the transcriptional regulator of TERT on this chromosome remains unclear. To examine the functional role of a putative hTERT regulator(s) on this chromosome, we transferred human chromosome 5 in a human melanoma cell line, A2058 cells by microcell-mediated chromosome transfer (MMCT). Microcell hybrid clones with an introduced chromosome 5, but not chromosome 10, showed a remarkable decrease in the growth rate with an obvious cellular morphological alteration and eventually cellular senescence. Moreover, this phenomenon was accompanied by a reduction of hTERT expression and telomerase activity. Most importantly, we found that transcriptional suppression of hTERT by the introduction of chromosome 5 is largely mediated by regulating hTERT promoter activity. Furthermore, the hTERT promote...Continue Reading

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Citations

Feb 9, 2011·Molecular and Cellular Biology·Dong-Lai QiHiroyuki Kugoh
Jul 28, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Marta GladychBlazej Rubis
Jan 6, 2016·Cancers·Hiroyuki KugohMitsuo Oshimura
Sep 28, 2015·Biochemical and Biophysical Research Communications·Sachiyo NishioHiroyuki Kugoh
Aug 14, 2019·PloS One·Takahito OhiraHiroyuki Kugoh

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