Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Virology (New York, N.Y.), 2015-02, Vol.476, p.271-288

Erscheinungsjahr

2015

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The human T-cell leukemia retrovirus type-1 (HTLV-1) p30 super(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 super(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 super(II) and c-MYC remain to be completely understood. Herein we demonstrate that p30 super(II) induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys arrow right Arg substitution mutants are impaired for oncogenic transformation with p30 super(II) in c-myc super(-/-) HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30 super(II) is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30 super(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 super(II)/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis.