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Please use this identifier to cite or link to this item: http://hdl.handle.net/10277/539

Authors: Abdallah, Rawan
Internal Tutor: TOSI, GIOVANNA
Title: Human tumor retrovirus-host-interaction: role of CIITA in the functional inhibition of HTLV-1 Tax-1 oncogenic protein.
Abstract: Human T-cell Lymphotropic Virus type-1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. Many evidences have shown that constitutive activation of NF-κB pathway by Tax-1 is crucial for T-cell transformation. Previous results demonstrated that CIITA, the master regulator of MHC class II gene transcription, inhibits HTLV-1 replication by blocking the transcription function of the viral transactivator Tax-1. Here we show that CIITA suppresses also Tax-1-mediated activation of the NF-κB pathway. CIITA interacts with and retains Tax-1 in the detergent unsoluble cell fraction (cytoplasmic debris) and inhibits Tax-1-dependent nuclear translocation of RelA. Moreover, the overexpression of CIITA does not affect Tax-1 interaction with both RelA and IKKγ. Nevertheless, the enzymatic activity of IKK kinase promoted by Tax-1 is impaired in the presence of CIITA. CIITA acts by suppressing at least the canonical NF-κB pathway, in that it also inhibits the activation of NF-κB by Tax-2, which is known to activate NF-κB through the canonical but not the non-canonical pathway. Overall, our results indicate that CIITA, beside acting as viral restriction factor against HTLV-1 infection, might counteract Tax-1 transforming activity. Thus, assessing the molecular basis of CIITA-mediated Tax-1 inhibition may be important in defining new strategies to control HTLV-1 spreading and oncogenic potential.
Keywords: CIITA, Tax-1, NF-κB, HTLV, oncogenesis.
Issue Date: 2014
Language: eng
Doctoral course: Medicina Sperimentale e Oncologia
Academic cycle: 26
Publisher: Università degli Studi dell'Insubria
Citation: Abdallah, R.Human tumor retrovirus-host-interaction: role of CIITA in the functional inhibition of HTLV-1 Tax-1 oncogenic protein. (Doctoral Thesis, Università degli Studi dell'Insubria, 2014).

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