Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1429-1438 |
| Number of pages | 10 |
| Journal | Cell Death and Differentiation |
| Volume | 12 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2005 |
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Keywords
- Apoptosis
- bcl-2
- Mitochondria
- Telomerase
ASJC Scopus subject areas
- Cell Biology
Cite this
Involvement of hTERT in apoptosis induced by interference with Bcl-2 expression and function. / Del Bufalo, D.; Rizzo, A.; Trisciuoglio, D.; Cardinali, G.; Torrisi, M. R.; Zangemeister-Wittke, U.; Zupi, G.; Biroccio, A.
In: Cell Death and Differentiation, Vol. 12, No. 11, 11.2005, p. 1429-1438.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Involvement of hTERT in apoptosis induced by interference with Bcl-2 expression and function
AU - Del Bufalo, D.
AU - Rizzo, A.
AU - Trisciuoglio, D.
AU - Cardinali, G.
AU - Torrisi, M. R.
AU - Zangemeister-Wittke, U.
AU - Zupi, G.
AU - Biroccio, A.
PY - 2005/11
Y1 - 2005/11
N2 - 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.
AB - 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.
KW - Apoptosis
KW - bcl-2
KW - Mitochondria
KW - Telomerase
UR - http://www.scopus.com/inward/record.url?scp=27344446189&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27344446189&partnerID=8YFLogxK
U2 - 10.1038/sj.cdd.4401670
DO - 10.1038/sj.cdd.4401670
M3 - Article
VL - 12
SP - 1429
EP - 1438
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
IS - 11
ER -