Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30II accessory protein and the induction of oncogenic cellular transformation by p30II/c-MYC

Megan M. Romeo, Bookyung Ko, Janice Kim, Rebecca Brady, Hayley C. Heatley, Jeffrey He, Carolyn K. Harrod, Braden Barnett, Lee Ratner, Michael Dale Lairmore, Ernest Martinez, Bernhard Lüscher, Craig N. Robson, Marie Henriksson, Robert Harrod

Research output: Contribution to journalArticle

8 Scopus citations

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 Lys→Arg substitution mutants are impaired for oncogenic transformation with p30II in c-myc-/- 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.

Original languageEnglish (US)
Pages (from-to)271-288
Number of pages18
JournalVirology
Volume476
DOIs
StatePublished - Feb 1 2015

Keywords

  • Acetylation
  • Apoptosis
  • C-MYC
  • HTLV-1
  • P30
  • Transformation

ASJC Scopus subject areas

  • Virology

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    Romeo, M. M., Ko, B., Kim, J., Brady, R., Heatley, H. C., He, J., Harrod, C. K., Barnett, B., Ratner, L., Lairmore, M. D., Martinez, E., Lüscher, B., Robson, C. N., Henriksson, M., & Harrod, R. (2015). Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30II accessory protein and the induction of oncogenic cellular transformation by p30II/c-MYC. Virology, 476, 271-288. https://doi.org/10.1016/j.virol.2014.12.008