Open Access
Article
Control of cell death pathways by HTLV-1 proteins
Daniela Saggioro1,Micol Silic-Benussi1,Roberta Biasiotto1,Donna M D'Agostino1,Vincenzo Ciminale1
1
Molecular Immunology and Oncology Unit, Istituto Oncologico Veneto-IRRCS, via Gattamelata 64, I-35128 Padova, Italy
DOI: 10.2741/3456 Volume 14 Issue 9, pp.3338-3351
Published: 01 January 2009
Abstract

Individuals infected with HTLV-1 harbor the virus mainly in CD4+ memory T-cells as a lifelong infection that remains subclinical in the majority of cases. However, about 3-5% of HTLV-1-infected individuals develop an aggressive T-cell neoplasia (ATLL) or a neurodegenerative disease (TSP/HAM) after a latency period ranging from years to decades. This review summarizes the current knowledge of the effects of the HTLV-1 proteins Tax, p13 and p12 on cell death and survival pathways. Tax, the major oncogenic determinant of HTLV-1, enhances cell survival through its effects on the NF-kappaB, CREB and AKT pathways and on the tumor suppressors p53 and Rb. p13 is targeted to the inner mitochondrial membrane and sensitizes cells to the Fas/ceramide apoptotic pathway and reactive oxygen species-mediated cell death. p12 enhances release of calcium from the endoplasmic reticulum and therefore may influence calcium-dependent apoptotic signals, including opening of the mitochondrial permeability transition pore. The long-term fate of HTLV-1-infected cells (apoptosis, survival, transformation) may therefore depend on the balance of the effects of Tax, p13 and p12 on cell death pathways.

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Daniela Saggioro, Micol Silic-Benussi, Roberta Biasiotto, Donna M D'Agostino, Vincenzo Ciminale. Control of cell death pathways by HTLV-1 proteins. Frontiers in Bioscience-Landmark. 2009. 14(9); 3338-3351.