The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis.

The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis.
Virology. 2018 Feb 17;518:103-115
Authors: Romeo M, Hutchison T, Malu A, White A, Kim J, Gardner R, Smith K, Nelson K, Bergeson R, McKee R, Harrod C, Ratner L, Lüscher B, Martinez E, Harrod R
Abstract
In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression. We therefore hypothesized that p53-regulated pro-survival signals may thwart the cell's metabolic anticancer defenses to support oncogene-activation in lymphoid cancers. Here we show that the Tp53-induced glycolysis and apoptosis regulator (TIGAR) promotes c-myc oncogene-activation by the human T-cell leukemia virus type-1 (HTLV-1) latency-maintenance factor p30II, associated with c-Myc deregulation in ATL clinical isolates. TIGAR prevents the intracellular accumulation of c-Myc-induced ROS and inhibits oncogene-induce...

Source: Virology - February 17, 2018 Category: Virology Authors: Romeo M, Hutchison T, Malu A, White A, Kim J, Gardner R, Smith K, Nelson K, Bergeson R, McKee R, Harrod C, Ratner L, Lüscher B, Martinez E, Harrod R Tags: Virology Source Type: research