Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor.
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.
Jin
Xun
X
Cell Growth Regulation Laboratory (CGRL), School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Beck
Samuel
S
Sohn
Young-Woo
YW
Kim
Jun-Kyum
JK
Kim
Sung-Hak
SH
Yin
Jinlong
J
Pian
Xumin
X
Kim
Sung-Chan
SC
Choi
Yun-Jaie
YJ
Kim
Hyunggee
H
D017209:Apoptosis; D020134:Catalytic Domain; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D004249:DNA Damage; D005333:Fetus / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000172:deficiency / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D016222:Fibroblast Growth Factor 2; C509186:TERT protein, human; D019098:Telomerase