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

作者：Romeo Megan M; Ko Bookyung; Kim Janice; Brady Rebecca; Heatley Hayley C; He Jeffrey; Harrod Carolyn K; Barnett Braden; Ratner Lee; Lairmore Michael D; Martinez Ernest; Luescher Bernhard; Robson Craig N; Henriksson Marie; Harrod Robert^*

来源：Virology, 2015, 476: 271-288.

DOI：10.1016/j.virol.2014.12.008

• HTLV-1
• p30
• c-MYC
• Acetylation
• Transformation
• Apoptosis

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 p3011 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.

• 出版日期2015-2