Article (Scientific journals)
Oncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase
Lefebvre, Laurent; Vanderplasschen, Alain; Ciminale, Vincenzo et al.
2002In Journal of Virology, 76 (3), p. 1400-1414
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Abstract :
[en] G4 and p13(II) are accessory proteins encoded by the X region of bovine leukemia virus and human T-cell leukemia virus type 1 (HTLV-1), respectively. Disruption of the G4 and p13(II) open reading frames interferes with viral spread in animal model systems, indicating that the corresponding proteins play a key role in viral replication. In addition, G4 is oncogenic in primary cell cultures and is absolutely required for efficient onset of leukemogenesis in sheep. To gain insight into the function of these proteins, we utilized the yeast two-hybrid system to identify protein partners of G4. Results revealed that G4 interacts with farnesyl pyrophosphate synthetase (FPPS), a protein involved in the mevalonate/squalene pathway and in synthesis of FPP, a substrate required for prenylation of Ras. The specificity of the interaction was verified by glutathione S-transferase (GST) pull-down assays and by coimmunoprecipitation experiments. Furthermore, confocal microscopy showed that the subcellular localization of G4 was profoundly affected by FPPS. The G4 protein itself was not prenylated, at least in rabbit reticulocyte lysate-based assays. The domain of G4 required for binding to FPPS was restricted to an amphipathic alpha-helix rich in arginine residues. Subtle mutation of this alpha-helix abrogated G4 oncogenic potential in vitro, providing a biological relevance for FPPS-G4 complex formation in cells. Finally, HTLV-1 p13(II) was also found to specifically interact with FPPS (in yeast as well as in GST pull-down assays) and to colocalize with G4 in mitochondria, suggesting a functional analogy between these oncoviral accessory proteins. Identification of FPPS as a molecular partner for p13(II) and G4 accessory proteins opens retrovirus-induced leukemia.
Disciplines :
Oncology
Immunology & infectious disease
Author, co-author :
Lefebvre, Laurent
Vanderplasschen, Alain ;  Université de Liège - ULiège > Immunologie et vaccinologie
Ciminale, Vincenzo
Heremans, Hubertine
Dangoisse, Olivier
Jauniaux, Jean-Claude
Toussaint, Jean-François
Zelnik, Vlado
Burny, Arsène ;  Université de Liège - ULiège > Agro Biotech Gembloux
Kettmann, Richard
Willems, Luc  ;  Université de Liège - ULiège > Chimie et bio-industries > Centre de Bio. Fond. - Section de Biologie cell. et moléc.
Language :
English
Title :
Oncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase
Publication date :
2002
Journal title :
Journal of Virology
ISSN :
0022-538X
eISSN :
1098-5514
Publisher :
Amer Soc Microbiology, Washington, United States - Washington
Volume :
76
Issue :
3
Pages :
1400-1414
1400-1414
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 24 November 2009

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