Involvement of hTERT in apoptosis induced by interference with Bcl-2 expression and function

D. Del Bufalo, A. Rizzo, D. Trisciuoglio, G. Cardinali, M. R. Torrisi, U. Zangemeister-Wittke, G. Zupi, A. Biroccio

Research output: Contribution to journalArticlepeer-review


Here, we investigated the role of telomerase on Bcl-2-dependent apoptosis. To this end, the 4625 Bcl-2/Bcl-xL bispecific antisense oligonucleotide and the HA14-1 Bcl-2 inhibitor were used. We found that apoptosis induced by 4625 oligonucleotide was associated with decreased Bcl-2 protein expression and telomerase activity, while HA14-1 triggered apoptosis without affecting both Bcl-2 and telomerase levels. Interestingly, HA14-1 treatment resulted in a profound change from predominantly nuclear to a predominantly cytoplasmic localization of hTERT. Downregulation of endogenous hTERT protein by RNA interference markedly increased apoptosis induced by both 4625 and HA14-1, while overexpression of wild-type hTERT blocked Bcl-2-dependent apoptosis in a p53-independent manner. Catalytically and biologically inactive hTERT mutants showed a similar behavior as the wild-type form, indicating that hTERT inhibited the 4625 and HA14-1-induced apoptosis regardless of telomerase activity and its ability to lengthening telomeres. Finally, hTERT overexpression abrogated 4625 and HA14-1-induced mitochondrial dysfunction and nuclear translocation of hTERT. In conclusion, our results demonstrate that hTERT is involved in mitochondrial apoptosis induced by targeted inhibition of Bcl-2.

Original languageEnglish
Pages (from-to)1429-1438
Number of pages10
JournalCell Death and Differentiation
Issue number11
Publication statusPublished - Nov 2005


  • Apoptosis
  • bcl-2
  • Mitochondria
  • Telomerase

ASJC Scopus subject areas

  • Cell Biology


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