Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30^II accessory protein and the induction of oncogenic cellular transformation by p30^II/c-MYC

The human T-cell leukemia retrovirus type-1 (HTLV-1) p30^II protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30^II interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30^II and c-MYC remain to be completely understood. Herein we demonstrate that p30^II induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30^II in c-myc^-/- HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30^II is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30^II inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30^II/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis.