Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6139675 | Virology | 2015 | 18 Pages |
Abstract
The human T-cell leukemia retrovirus type-1 (HTLV-1) p30II 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 p30II 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 p30II and c-MYC remain to be completely understood. Herein we demonstrate that p30II induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC LysâArg substitution mutants are impaired for oncogenic transformation with p30II in c-mycâ/â HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30II is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30II 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 p30II/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis.
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Authors
Megan M. Romeo, Bookyung Ko, Janice Kim, Rebecca Brady, Hayley C. Heatley, Jeffrey He, Carolyn K. Harrod, Braden Barnett, Lee Ratner, Michael D. Lairmore, Ernest Martinez, Bernhard Lüscher, Craig N. Robson, Marie Henriksson, Robert Harrod,