The Major Histocompatibility Complex Class II Transactivator CIITA Inhibits the Persistent Activation of NF-κB by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein

Journal of Virology
Greta ForlaniGiovanna Tosi

Abstract

Human T cell lymphotropic virus type 1 (HTLV-1) Tax-1, a key protein in HTLV-1-induced T cell transformation, deregulates diverse cell signaling pathways. Among them, the NF-κB pathway is constitutively activated by Tax-1, which binds to NF-κB proteins and activates the IκB kinase (IKK). Upon phosphorylation-dependent IκB degradation, NF-κB migrates into the nucleus, mediating Tax-1-stimulated gene expression. We show that the transcriptional regulator of major histocompatibility complex class II genes CIITA (class II transactivator), endogenously or ectopically expressed in different cells, inhibits the activation of the canonical NF-κB pathway by Tax-1 and map the region that mediates this effect. CIITA affects the subcellular localization of Tax-1, which is mostly retained in the cytoplasm, and this correlates with impaired migration of RelA into the nucleus. Cytoplasmic and nuclear mutant forms of CIITA reveal that CIITA exploits different strategies to suppress Tax-1-mediated NF-κB activation in both subcellular compartments. CIITA interacts with Tax-1 without preventing Tax-1 binding to both IKKγ and RelA. Nevertheless, CIITA affects Tax-1-induced IKK activity, causing retention of the inactive p50/RelA/IκB complex in the...Continue Reading

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Citations

Apr 20, 2016·Journal of Translational Medicine·Greta ForlaniGiovanna Tosi
Jan 10, 2018·Frontiers in Microbiology·Marco BaratellaRoberto S Accolla
Mar 9, 2018·Frontiers in Microbiology·Stefania FochiMaria G Romanelli
Jan 31, 2018·Frontiers in Microbiology·Hélène GazonLuc Willems
Mar 12, 2019·F1000Research·Yutaka TagayaRobert Gallo
Dec 15, 2019·Pathogens·Stefania FochiMaria Grazia Romanelli
Sep 24, 2020·Molecular & Cellular Proteomics : MCP·Greta ForlaniMichal Bassani-Sternberg
Jan 28, 2021·International Journal of Molecular Sciences·Jorge Alfonso León Machado, Viktor Steimle
Feb 17, 2021·Molecular & Cellular Proteomics : MCP·Greta ForlaniMichal Bassani-Sternberg
Aug 8, 2021·International Journal of Molecular Sciences·Greta ForlaniMaria Grazia Romanelli

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