title: Human telomerase catalytic subunit (hTERT) suppresses p53-mediated anti-apoptotic response via induction of basic fibroblast growth factor.
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.
authors.affiliation: Cell Growth Regulation Laboratory (CGRL), School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Xun
authors.initials: X
authors.lastname: Jin
authors.forename: Samuel
authors.initials: S
authors.lastname: Beck
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Sohn
authors.forename: Jun-Kyum
authors.initials: JK
authors.lastname: Kim
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Kim
authors.forename: Jinlong
authors.initials: J
authors.lastname: Yin
authors.forename: Xumin
authors.initials: X
authors.lastname: Pian
authors.forename: Sung-Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: 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*
chemical_list: D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D016222:Fibroblast Growth Factor 2; C509186:TERT protein, human; D019098:Telomerase