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.

Human tumor retrovirus-host-interaction: role of CIITA in the functional inhibition of HTLV-1 Tax-1 oncogenic protein / Abdallah, Rawan. - (2014).

Human tumor retrovirus-host-interaction: role of CIITA in the functional inhibition of HTLV-1 Tax-1 oncogenic protein.

Abdallah, Rawan
2014

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.
CIITA, Tax-1, NF-κB, HTLV, oncogenesis.
Human tumor retrovirus-host-interaction: role of CIITA in the functional inhibition of HTLV-1 Tax-1 oncogenic protein / Abdallah, Rawan. - (2014).
File in questo prodotto:
File Dimensione Formato  
PhD_thesis_abdallahrawan_completa.pdf

embargo fino al 05/02/2016

Descrizione: testo completo tesi
Tipologia: Tesi di dottorato
Licenza: Non specificato
Dimensione 4.2 MB
Formato Adobe PDF
4.2 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2090355
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact