Abstract
Defects in the regulation of programmed cell death play a fundamental role in the development of neoplasia and neurological disorders, both of which are linked to the human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection. We previously showed that the HTLV-1 Tax protein protects from apoptosis induced by serum starvation by preventing cytochrome c release and Bax relocation to mitochondria, two early events in the mitochondrial apoptotic pathway. As a natural extension of these findings, and to better define the action of Tax, in the present study, we investigated the outcome of Tax and two mutants which are inactive in CREB/ATF (M47) or NF-κB (M22) pathways, in the control of apoptosis induced by the proapoptotic Bax protein. We found that activation of CREB, rather than NF-κB, is a key phenomenon in preventing apoptosis. Furthermore, the importance of CREB activation is strengthened by experiments with CREB mutants, treatment with forskolin, and in situ analysis of P-CREB status in cells transfected with Tax or its nonprotecting M47 mutant. Considered together, these results underscore a primary role of CREB in preventing apoptosis triggered by Bax, and suggest that Tax might act by affecting the phosphorylation state of CREB.
| Original language | English |
|---|---|
| Pages (from-to) | 1390-1400 |
| Number of pages | 11 |
| Journal | Experimental Cell Research |
| Volume | 312 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - May 1 2006 |
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Keywords
- Apoptosis
- Bax
- CREB-133
- Forskolin
- K-CREB
- Phospho-CREB
- Tax
ASJC Scopus subject areas
- Cell Biology
Cite this
Antiapoptotic effect of human T-cell leukemia virus type 1 tax protein correlates with its creb transcriptional activity. / Trevisan, Roberta; Daprai, Laura; Paloschi, Lucia; Vajente, Nicola; Chieco-Bianchi, Luigi; Saggioro, Daniela.
In: Experimental Cell Research, Vol. 312, No. 8, 01.05.2006, p. 1390-1400.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antiapoptotic effect of human T-cell leukemia virus type 1 tax protein correlates with its creb transcriptional activity
AU - Trevisan, Roberta
AU - Daprai, Laura
AU - Paloschi, Lucia
AU - Vajente, Nicola
AU - Chieco-Bianchi, Luigi
AU - Saggioro, Daniela
PY - 2006/5/1
Y1 - 2006/5/1
N2 - Defects in the regulation of programmed cell death play a fundamental role in the development of neoplasia and neurological disorders, both of which are linked to the human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection. We previously showed that the HTLV-1 Tax protein protects from apoptosis induced by serum starvation by preventing cytochrome c release and Bax relocation to mitochondria, two early events in the mitochondrial apoptotic pathway. As a natural extension of these findings, and to better define the action of Tax, in the present study, we investigated the outcome of Tax and two mutants which are inactive in CREB/ATF (M47) or NF-κB (M22) pathways, in the control of apoptosis induced by the proapoptotic Bax protein. We found that activation of CREB, rather than NF-κB, is a key phenomenon in preventing apoptosis. Furthermore, the importance of CREB activation is strengthened by experiments with CREB mutants, treatment with forskolin, and in situ analysis of P-CREB status in cells transfected with Tax or its nonprotecting M47 mutant. Considered together, these results underscore a primary role of CREB in preventing apoptosis triggered by Bax, and suggest that Tax might act by affecting the phosphorylation state of CREB.
AB - Defects in the regulation of programmed cell death play a fundamental role in the development of neoplasia and neurological disorders, both of which are linked to the human T-cell leukemia/lymphoma virus type 1 (HTLV-1) infection. We previously showed that the HTLV-1 Tax protein protects from apoptosis induced by serum starvation by preventing cytochrome c release and Bax relocation to mitochondria, two early events in the mitochondrial apoptotic pathway. As a natural extension of these findings, and to better define the action of Tax, in the present study, we investigated the outcome of Tax and two mutants which are inactive in CREB/ATF (M47) or NF-κB (M22) pathways, in the control of apoptosis induced by the proapoptotic Bax protein. We found that activation of CREB, rather than NF-κB, is a key phenomenon in preventing apoptosis. Furthermore, the importance of CREB activation is strengthened by experiments with CREB mutants, treatment with forskolin, and in situ analysis of P-CREB status in cells transfected with Tax or its nonprotecting M47 mutant. Considered together, these results underscore a primary role of CREB in preventing apoptosis triggered by Bax, and suggest that Tax might act by affecting the phosphorylation state of CREB.
KW - Apoptosis
KW - Bax
KW - CREB-133
KW - Forskolin
KW - K-CREB
KW - Phospho-CREB
KW - Tax
UR - http://www.scopus.com/inward/record.url?scp=33646045581&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646045581&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2006.01.009
DO - 10.1016/j.yexcr.2006.01.009
M3 - Article
VL - 312
SP - 1390
EP - 1400
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 8
ER -