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

Starting date
January 1, 2011
Duration (months)
36
Managers or local contacts
Romanelli Maria
Keyword
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.

Sponsors:

PRIN VALUTATO POSITIVAMENTE
Funds: requested
Syllabus: PRIN

Project participants

Erica Diani
Scholarship holder
Pamela Lorenzi
Technical-administrative staff
Maria Romanelli
Associate Professor
Antonino Stefano Suraci
Technical-administrative staff
Research areas involved in the project
Biology

Activities

Research facilities