title: Control of cell death pathways by HTLV-1 proteins.
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.
authors.affiliation: Molecular Immunology and Oncology Unit, Istituto Oncologico Veneto-IRRCS, via Gattamelata 64, I-35128 Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Saggioro
authors.forename: Micol
authors.initials: M
authors.lastname: Silic-Benussi
authors.forename: Roberta
authors.initials: R
authors.lastname: Biasiotto
authors.forename: Donna M
authors.initials: DM
authors.lastname: D'Agostino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ciminale
mesh_terms: D016923:Cell Death / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival; D006706:Homeostasis; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology*; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D014764:Viral Proteins