Università degli Studi dell'Insubria Insubria Space
 

InsubriaSPACE - Thesis PhD Repository >
Insubria Thesis Repository >
01 - Tesi di dottorato >

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10277/539

Autori: Abdallah, Rawan
Tutor interno: TOSI, GIOVANNA
ACCOLLA, ROBERTO
Titolo: 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.
Parole chiave: CIITA, Tax-1, NF-κB, HTLV, oncogenesis.
MIUR : MED/04 PATOLOGIA GENERALE
Data: 2014
Lingua: eng
Corso di dottorato: Medicina Sperimentale e Oncologia
Ciclo di dottorato: 26
Università di conseguimento titolo: Università degli Studi dell'Insubria
Citazione: 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).

Full text:

File Descrizione DimensioniFormatoConsultabilità
PhD_thesis_abdallahrawan_completa.pdftesto completo tesi4,2 MBAdobe PDFVisualizza/apri

Questo documento è distribuito in accordo con Licenza Creative Commons
Creative Commons


Tutti i documenti archiviati in InsubriaSPACE sono protetti da copyright. Tutti i diritti riservati.


Segnala questo record su
Del.icio.us

Citeulike

Connotea

Facebook

Stumble it!

reddit


 

  ICT Support, development & maintenance are provided by the AePIC team @ CILEA. Powered on DSpace Software.  Feedback