The importance of ubiquitination and sumoylation on the transforming activity of HTLV Tax-1 and Tax-2

Retrovirology

Kuan-Teh Jeang¹  Linda Zane¹ 

[1] Molecular Virology Section, Laboratory of Molecular Microbiology, the National Institutes of Allergy and Infectious Diseases, the National Institutes of Health, Bethesda, MD, 20892-0460, USA

关键词: Ubiquitination;    Sumoylation;    NF-κB;    Cell transformation;    ATL;    Tax;    HTLV-2;    HTLV-1;   

Others  :  1209221
DOI  :  10.1186/1742-4690-9-103

 received in 2012-11-27, accepted in 2012-11-29,  发布年份 2012

【 摘 要 】

Human T-cell Leukemia Virus type 1 (HTLV-1) and 2 (HTLV-2) are two closely related human retroviruses. HTLV-1 is associated with an aggressive Adult T-cell Leukemia (ATL) while there is no evidence for an association of HTLV-2 with any human malignancies. The two viruses encode transactivator proteins, Tax-1 and Tax-2 respectively. In ATL, Tax-1 is thought to play a central role in the transformation of a normal T-cell into a leukemic cell; however, it has not been entirely clear how post-translational modifications of Tax-1 influence its transforming activity. Here, we discuss three recent papers that report on the ubiquitination and sumoylation of Tax-1 and Tax-2. We comment on their divergent findings implicating the importance (or lack of importance) of these modifications and other events on Tax activation of NF-κB as related to cellular transformation.

【 授权许可】

   
2012 Zane and Jeang; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Kannian P, Yin H, Doueiri R, Lairmore MD, Fernandez S, Green PL: Distinct transformation tropism exhibited by human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 is the result of postinfection T cell clonal expansion. J Virol 2012, 86(7):3757-3766.
• [2]Martin FBC, Ciminale V, Lairmore MD, Murphy EL, Switzer WM, Mahieux R: Conference highlights of the 15th international conference on human retrovirology: HTLV and related retroviruses, 4–8 june 2011, Leuven, Gembloux, Belgium. Retrovirology 2011, 8:86. BioMed Central Full Text
• [3]Kirk PD, Witkover A, Courtney A, Lewin AM, Wait R, Stumpf MP, Richardson S, Taylor GP, Bangham CR: Plasma proteome analysis in HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology 2011, 8:81. BioMed Central Full Text
• [4]Shoji T, Higuchi M, Kondo R, Takahashi M, Oie M, Tanaka Y, Aoyagi Y, Fujii M: Identification of a novel motif responsible for the distinctive transforming activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2 Tax2. Retrovirology 2009, 6:83. BioMed Central Full Text
• [5]Chaturvedi MM, Sung B, Yadav VR, Kannappan R, Aggarwal BB: NF-kappaB addiction and its role in cancer: 'one size does not fit all'. Oncogene 2011, 30(14):1615-1630.
• [6]Bonnet A, Randrianarison-Huetz V, Nzounza P, Nedelec M, Chazal M, Waast L, Pene S, Bazarbachi A, Mahieux R, Benit L, et al.: Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation. Retrovirology 2012, 9:77. BioMed Central Full Text
• [7]Journo C, Bonnet A, Favre-Bonvin A, Turpin J, Vinera J, Cote E, Chevalier SA, Kfoury Y, Bazarbachi A, Pique C, et al.: HTLV-2 Tax-mediated NF-kappaB activation involves a mechanism independent of Tax conjugation to ubiquitin and SUMO. J Virol 2012.
• [8]Turci MLJ, Di Gennaro G, Rinaldi AS, Marin O, Diani E, Sampaio C, Bex F, Bertazzoni U, Romanelli MG: Ubiquitination and sumoylation of the HTLV-2 Tax-2B protein regulate its NF-kB activity: a comparative study with the HTLV-1 Tax-1 protein. Retrovirology 2012.
• [9]Hay RT: SUMO: a history of modification. Mol Cell 2005, 18(1):1-12.
• [10]Hjerpe R, Rodriguez MS: Efficient approaches for characterizing ubiquitinated proteins. Biochem Soc Trans 2008, 36(Pt 5):823-827.
• [11]Xiao G: NF-kappaB activation: Tax sumoylation is out, but what about Tax ubiquitination? Retrovirology 2012, 9:78. BioMed Central Full Text
• [12]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144(5):646-674.
• [13]Majone F, Jeang KT: Unstabilized DNA breaks in HTLV-1 Tax expressing cells correlate with functional targeting of Ku80, not PKcs, XRCC4, or H2AX. Cell & bioscience 2012, 2(1):15. BioMed Central Full Text
• [14]Chi YH, Jeang KT: Aneuploidy and cancer. J Cell Biochem 2007, 102(3):531-538.
• [15]Zane L, Sibon D, Jeannin L, Zandecki M, Delfau-Larue MH, Gessain A, Gout O, Pinatel C, Lancon A, Mortreux F, et al.: Tax gene expression and cell cycling but not cell death are selected during HTLV-1 infection in vivo. Retrovirology 2010, 7:17. BioMed Central Full Text