Abstract 5347: Disruption of PDZ protein-protein interactions inhibits Tax transformation and HTLV-1 infection capacities

Abstract

Abstract Approximately 15 to 25 million people worldwide are infected with human T-cell leukaemia virus type 1 (HTLV-1) or type 2 (HTLV-2). One of the viral regulatory proteins, Tax, is critical for viral transcription and replication and has been clearly implicated in T-lymphocyte transformation in vitro and oncogenesis in vivo. Elucidation of the metabolic processes involved in Tax activity is thus of prime importance for understanding the pathogenesis induce by HTLV. Interactions between Tax and a selected group of PDZ containing proteins are associated with the transforming activities of Tax1 as well as persistent HTLV-1 infection. We demonstrate that the PDZ-containing protein syntenin-1 and −2, known to interact with Heparan sulfate proteoglycan receptor syndecan-1 and to connect cytoskeletal proteins, interact with HTLV-1 Tax and with the HTLV-1 receptor GLUT-1 but not with HTLV-2 Tax. Both PDZ1 and 2 domains of syntenins are required for Tax binding. We also show that syntenin-2 co-localizes with Tax in nuclear speckles. Furthermore, we demonstrate that an antagonist for PDZ protein- protein interaction suppresses Tax-induced transformation and prevents T cell infection by HTLV-1. Thus, disruption of PDZ protein-protein interaction may provide new therapeutic opportunities for HTLV-1 induced diseases. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5347.