title: 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.
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 p30(II) 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.
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Romeo
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Bookyung
authors.initials: B
authors.lastname: Ko
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Brady
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Hayley C
authors.initials: HC
authors.lastname: Heatley
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: He
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Harrod
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA.
authors.forename: Braden
authors.initials: B
authors.lastname: Barnett
authors.affiliation: Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Ratner
authors.affiliation: University of California-Davis, School of Veterinary Medicine, One Shields Avenue, Davis, CA 95618, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Lairmore
authors.affiliation: Department of Biochemistry, University of California, Riverside, CA 92521, USA.
authors.forename: Ernest
authors.initials: E
authors.lastname: Martinez
authors.affiliation: Institute of Biochemistry, Klinikum, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.affiliation: Northern Institute for Cancer Research, Newcastle University, The Medical School, Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Robson
authors.affiliation: Department of Microbiology, Cell and Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Henriksson
authors.affiliation: Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design, and Delivery, Southern Methodist University, Dallas, TX 75275-0376, USA. Electronic address: rharrod@smu.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Harrod
mesh_terms: D000107:Acetylation; D020816:Amino Acid Motifs; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D015490:HTLV-I Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012191:Retroviridae Proteins; C072814:tof protein, Human T-lymphotropic virus 1
keywords: Acetylation; Apoptosis; HTLV-1; Transformation; c-MYC; p30