Influenza dei geni espressi da HTLV nella trasformazione e nel turnover delle cellule T e identificazione di nuovi bersagli terapeutici

Data inizio
1 gennaio 2011
Durata (mesi) 
36
Responsabili (o referenti locali)
Romanelli Maria
Parole chiave
HTLV, cancer, signal transduction

This research project intends to gain insight into the molecular mechanisms of T cell transformation derived by human T-cell leukemia virus type (HTLV) infection and identify novel therapeutic targets. It is focused on the study of the structure and function of the HTLV Tax oncoproteins and their role in the trasductional signaling pathways to understand the mechanisms through which Tax influences viral pathogenesis. The expression of Tax proteins in human cells will be studied to identify cellular localization, interaction with cellular factors and postranslational modifications in order to define the molecular basis of the oncogenic differences between the two retroviruses. Studying Tax interactions with cellular factors will allow to define the homology and difference between Tax-1 and Tax-2 in the NF-kB pathway induction. Tax drives neoplastic transformation by controlling cell turnover through the activation of the expression of cytokines responsible for T cell proliferation, by suppressing apoptosis and by increasing genetic instability. Tax transgenic mice develop T cell lymphomas, demonstrating that Tax is necessary and sufficient to transform T-cells in vivo. However, it is still unclear which additional viral and/or cellular genes may tip the balance between clinically silent infection and progression to ATLL, which occurs in about 3% of infected individuals after decades of latency. It is known that HTLV- 2 has a reduced pathogenicity compared to HTLV-1 Since the difference in phatogenicity between HTLV-1 and HTLV-2 is generally attributed to Tax-1 and Tax-2, in this work we compared the properties of the Tax proteins to better understand their role in the differential pathogenicity.

Enti finanziatori:

PRIN VALUTATO POSITIVAMENTE
Finanziamento: richiesto
Programma: PRIN

Partecipanti al progetto

Erica Diani
Pamela Lorenzi
Tecnico-Amministrativo
Maria Romanelli
Professore associato
Antonino Stefano Suraci
Tecnico-Amministrativo
Aree di ricerca coinvolte dal progetto
Biology

Attività

Strutture