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Acetylation at lysine 346 controls the transforming activity of the HTLV-1 Tax oncoprotein in the Rat-1 fibroblast model.
Lodewick, Julie; Sampaio, Carla; Boxus, Mathieu; Rinaldi, Anne-Sophie; Coulonval, Katia; Willems, Luc; Roger, Pierre P; Bex, Françoise.
Afiliación
  • Lodewick J; Institute for Microbiological Research J-M Wiame (IRMW), Laboratory of Microbiology, Université Libre de Bruxelles, 1, Avenue E, Gryson, Brussels, Belgium.
Retrovirology ; 10: 75, 2013 Jul 23.
Article en En | MEDLINE | ID: mdl-23880157
BACKGROUND: Transformation by the Tax oncoprotein of the human T cell leukemia virus type 1 (HTLV-1) is governed by actions on cellular regulatory signals, including modulation of specific cellular gene expression via activation of signaling pathways, acceleration of cell cycle progression via stimulation of cyclin-dependent kinase activity leading to retinoblastoma protein (pRb) hyperphosphorylation and perturbation of survival signals. These actions control early steps in T cell transformation and development of Adult T cell leukemia (ATL), an aggressive malignancy of HTLV-1 infected T lymphocytes. Post-translational modifications of Tax by phosphorylation, ubiquitination, sumoylation and acetylation have been implicated in Tax-mediated activation of the NF-κB pathway, a key function associated with Tax transforming potential. RESULTS: In this study, we demonstrate that acetylation at lysine K(346) in the carboxy-terminal domain of Tax is modulated in the Tax nuclear bodies by the acetyltransferase p300 and the deacetylases HDAC5/7 and controls phosphorylation of the tumor suppressor pRb by Tax-cyclin D3-CDK4-p21(CIP) complexes. This property correlates with the inability of the acetylation deficient K(346)R mutant, but not the acetylation mimetic K(346)Q mutant, to promote anchorage-independent growth of Rat-1 fibroblasts. By contrast, acetylation at lysine K(346) had no effects on the ability of Tax carboxy-terminal PDZ-binding domain to interact with the tumor suppressor hDLG. CONCLUSIONS: The identification of the acetyltransferase p300 and the deacetylase HDAC7 as enzymes modulating Tax acetylation points to new therapeutic targets for the treatment of HTLV-1 infected patients at risk of developing ATL.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Virus Linfotrópico T Tipo 1 Humano / Transformación Celular Viral / Procesamiento Proteico-Postraduccional / Productos del Gen tax / Factores de Transcripción p300-CBP / Histona Desacetilasas / Lisina Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Retrovirology Asunto de la revista: VIROLOGIA Año: 2013 Tipo del documento: Article País de afiliación: Bélgica

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Virus Linfotrópico T Tipo 1 Humano / Transformación Celular Viral / Procesamiento Proteico-Postraduccional / Productos del Gen tax / Factores de Transcripción p300-CBP / Histona Desacetilasas / Lisina Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Retrovirology Asunto de la revista: VIROLOGIA Año: 2013 Tipo del documento: Article País de afiliación: Bélgica