TY - JOUR
T1 - Relevance of CREB phosphorylation in the anti-apoptotic function of human T-lymphotropic virus type 1 tax protein in serum-deprived murine fibroblasts
AU - Trevisan, Roberta
AU - Daprai, Laura
AU - Acquasaliente, Lidia
AU - Ciminale, Vincenzo
AU - Chieco-Bianchi, Luigi
AU - Saggioro, Daniela
PY - 2004/9/10
Y1 - 2004/9/10
N2 - The human T-cell leukemia virus type 1 (HTLV-1) Tax transactivator is thought to play a primary role in the development of HTLV-1-mediated diseases. Using a murine fibroblast model, we previously showed that Tax reduces apoptosis induced by serum starvation by preventing cytochrome c release from the mitochondria. As Tax can enhance the transcriptional activity of nuclear factor NF-kB and cAMP-responsive element binding protein/activating transcription factor-1 (CREB/ATF-1), we investigated the relevance of these routes in the anti-apoptotic effects of Tax. Results showed that a Tax mutant retaining CREB/ATF-1 transactivating activity protects murine fibroblasts from serum-depletion-induced apoptosis, while two CREB/ATF-1-defective mutants did not. Treatment with forskolin, an activator of CREB, significantly attenuated cytochrome c release and Bax translocation in response of serum deprivation. In analogy to forskolin treatment, Tax expression results in sustained phosphorylation of CREB at Ser133 during serum starvation. Considered together, these results underscore a primary role of CREB transcriptional activation in preventing apoptosis triggered by growth factor withdrawal, and suggest that Tax might in part function by affecting the phosphorylation state of CREB.
AB - The human T-cell leukemia virus type 1 (HTLV-1) Tax transactivator is thought to play a primary role in the development of HTLV-1-mediated diseases. Using a murine fibroblast model, we previously showed that Tax reduces apoptosis induced by serum starvation by preventing cytochrome c release from the mitochondria. As Tax can enhance the transcriptional activity of nuclear factor NF-kB and cAMP-responsive element binding protein/activating transcription factor-1 (CREB/ATF-1), we investigated the relevance of these routes in the anti-apoptotic effects of Tax. Results showed that a Tax mutant retaining CREB/ATF-1 transactivating activity protects murine fibroblasts from serum-depletion-induced apoptosis, while two CREB/ATF-1-defective mutants did not. Treatment with forskolin, an activator of CREB, significantly attenuated cytochrome c release and Bax translocation in response of serum deprivation. In analogy to forskolin treatment, Tax expression results in sustained phosphorylation of CREB at Ser133 during serum starvation. Considered together, these results underscore a primary role of CREB transcriptional activation in preventing apoptosis triggered by growth factor withdrawal, and suggest that Tax might in part function by affecting the phosphorylation state of CREB.
KW - Apoptosis
KW - Bax
KW - Cytochrome c
KW - Forskolin
KW - HTLV-1
KW - P-CREB
KW - Tax
UR - http://www.scopus.com/inward/record.url?scp=4043074186&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4043074186&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2004.05.024
DO - 10.1016/j.yexcr.2004.05.024
M3 - Article
C2 - 15302573
AN - SCOPUS:4043074186
VL - 299
SP - 57
EP - 67
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -