Article (Scientific journals)
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 et al.
2013In Retrovirology, 2013 (10), p. 75
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Keywords :
HTLV-1; Tax; acetylation; CDK4; transformation; leukemia
Abstract :
[en] 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-B pathway, a key function associated with Tax transforming potential. Results In this study, we demonstrate that acetylation at lysine K346 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-p21CIP complexes. This property correlates with the inability of the acetylation deficient K346R mutant, but not the acetylation mimetic K346Q mutant, to promote anchorage-independent growth of Rat-1 fibroblasts. By contrast, acetylation at lysine K346 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.
Disciplines :
Author, co-author :
Lodewick, Julie;  Université Libre de Bruxelles - ULB > IRMW
Sampaio, Carla
Boxus, Mathieu
Rinaldi, Anne-Sophie
Coulonval, Katia
Willems, Luc  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Roger, Pierre;  Université Libre de Bruxelles - ULB
Bex, Françoise
Language :
Title :
Acetylation at lysine 346 controls the transforming activity of the HTLV-1 Tax oncoprotein in the Rat-1 fibroblast model
Publication date :
23 July 2013
Journal title :
Publisher :
BioMed Central, London, United Kingdom
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
This work was supported by grants from the Belgian Fonds de la Recherche Scientifique Médicale (FRSM), from the FNRS-Télévie, from the Internationale Brachet Stiftung, the Belgian Foundation against Cancer (2010-172 to PPR).
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