Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor

Xun Jin, Samuel Beck, Young Woo Sohn, Jun Kyum Kim, Sung Hak Kim, Jinlong Yin, Xumin Pian, Sung Chan Kim, Yun Jaie Choi, Hyunggee Kim

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Although human telomerase catalytic subunit (TERT) has several cellular functions including telomere homeostasis, genomic stability, cell proliferation, and tumorigenesis, the molecular mechanism underlying anti-apoptosis regulated by TERT remains to be elucidated. Here, we show that ectopic expression of TERT in spontaneously immortalized human fetal fibroblast (HFFS) cells, which are a telomerase- and p53-positive, leads to increases of cell proliferation and transformation, as well as a resistance to DNA damage response and inactivation of p53 function. We found that TERT and a mutant TERT (no telomerase activity) induce expression of basic fibroblast growth factor (bFGF), and ectopic expression of bFGF also allows cells to be resistant to DNA-damaging response and to suppress activation of p53 function under DNA-damaging induction. Furthermore, loss of TERT or bFGF markedly increases a p53 activity and DNA-damage sensitivity in HFFS, HeLa and U87MG cells. Therefore, our findings indicate that a novel TERT-bFGF axis accelerates the inactivation of p53 and consequent increase of resistance to DNA-damage response.

Original languageEnglish
Pages (from-to)574-582
Number of pages9
JournalExperimental and Molecular Medicine
Volume42
Issue number8
DOIs
Publication statusPublished - 2010

Keywords

  • Apoptosis
  • Cell death
  • Fibroblast growth factor 2
  • Telomerase
  • Tumor suppressor protein p53

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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