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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

Lookup NU author(s): Professor Craig RobsonORCiD

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Abstract

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. (C) 2014 Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Romeo MM, Ko B, Kim J, Brady R, Heatley HC, He J, Harrod CK, Barnett B, Ratner L, Lairmore MD, Martinez E, Luscher B, Robson CN, Henriksson M, Harrod R

Publication type: Article

Publication status: Published

Journal: Virology

Year: 2015

Volume: 476

Pages: 271-288

Print publication date: 01/02/2015

Online publication date: 05/01/2015

Acceptance date: 05/12/2014

ISSN (print): 0042-6822

ISSN (electronic): 1096-0341

Publisher: Academic Press

URL: http://dx.doi.org/10.1016/j.virol.2014.12.008

DOI: 10.1016/j.virol.2014.12.008

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