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

• Published in: Retrovirology Vol. 9; no. 1; p. 102
• Main Authors: Turci, Marco, Lodewick, Julie, Di Gennaro, Gianfranco, Rinaldi, Anne Sophie, Marin, Oriano, Diani, Erica, Sampaio, Carla, Bex, Françoise, Bertazzoni, Umberto, Romanelli, Maria Grazia
• Format: Journal Article
• Language: English
• Published: London BioMed Central 01.01.2012
• Subjects: Adult T cell leukemia; Amino acids; Arginine; C-Terminus; Cell cycle; Cell survival; Colleges & universities; Comparative analysis; Deficient mutant; Gene expression; Genetics; genomics; Golgi apparatus; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Infection; Kinases; Lymphocytes T; Lysine; Mutation; Neoplasia; NF- Kappa B protein; Pathogenicity; Phosphorylation; Plasmids; Post-translation; Proteins; RelA protein; Retrovirus; SUMO protein; Transcription; Transformation; Ubiquitin; ubiquitination
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/1742-4690-9-102

Doc number: 102 Abstract 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.