Ubiquitination and sumoylation of the HTLV-2 Tax-2B protein regulate its NF-κB activity: a comparative study with the HTLV-1 Tax-1 protein

Retrovirology

Maria Grazia Romanelli³  Umberto Bertazzoni³  Françoise Bex¹  Carla Sampaio¹  Erica Diani³  Oriano Marin²  Anne Sophie Rinaldi¹  Gianfranco Di Gennaro³  Julie Lodewick¹  Marco Turci³ 

[1] Institute for Microbiological Research J-M Wiame, Laboratory of Microbiology, Université Libre de Bruxelles, 1, Avenue E. Gryson, Brussels, Belgium;Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy;Department of Life and Reproduction Sciences, Section of Biology and Genetics, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy

关键词: NF-κB pathway;    Sumoylation;    Ubiquitination;    Post-translational modification;    Leukemia;    Oncoprotein;    Tax;    Retrovirus;    HTLV-2;    HTLV-1;   

Others  :  1209222
DOI  :  10.1186/1742-4690-9-102

 received in 2012-04-18, accepted in 2012-11-02,  发布年份 2012

【 摘 要 】

Background

Retroviruses HTLV-1 and HTLV-2 have homologous genomic structures but differ significantly in pathogenicity. HTLV-1 is associated with Adult T cell Leukemia (ATL), whereas infection by HTLV-2 has no association with neoplasia. Transformation of T lymphocytes by HTLV-1 is linked to the capacity of its oncoprotein Tax-1 to alter cell survival and cell cycle control mechanisms. Among these functions, Tax-1-mediated activation of cellular gene expression via the NF-κB pathway depends on Tax-1 post-translational modifications by ubiquitination and sumoylation. The Tax-2 protein of HTLV-2B (Tax-2B) is also modified by ubiquitination and sumoylation and activates the NF-κB pathway to a level similar to that of Tax-1. The present study aims to understand whether ubiquitination and sumoylation modifications are involved in Tax-2B-mediated activation of the NF-κB pathway.

Results

The comparison of Tax-1 and Tax-2B lysine to arginine substitution mutants revealed conserved patterns and levels of ubiquitination with notable difference in the lysine usage for sumoylation. Neither Tax-1 nor Tax-2B ubiquitination and sumoylation deficient mutants could activate the NF-κB pathway and fusion of ubiquitin or SUMO-1 to the C-terminus of the ubiquitination and sumoylation deficient Tax-2B mutant strikingly restored transcriptional activity. In addition, ubiquitinated forms of Tax-2B colocalized with RelA and IKKγ in prominent cytoplasmic structures associated with the Golgi apparatus, whereas colocalization of Tax-2B with the RelA subunit of NF-κB and the transcriptional coactivator p300 in punctate nuclear structures was dependent on Tax-2B sumoylation, as previously observed for Tax-1.

Conclusions

Both Tax-1 and Tax-2 activate the NF-κB pathway via similar mechanisms involving ubiquitination and sumoylation. Therefore, the different transforming potential of HTLV-1 and HTLV-2 is unlikely to be related to different modes of activation of the canonical NF-κB pathway.

【 授权许可】

   
2012 Turci et al.; licensee BioMed Central Ltd.

【 图 表 】

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