THE SYT PROTEIN INVOLVED IN THE T(X-18) SYNOVIAL SARCOMA TRANSLOCATION IS A TRANSCRIPTIONAL ACTIVATOR LOCALIZED IN NUCLEAR-BODIES

The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas resu lts in the fusion of the SYT gene on chromosome 18 to either of two cl osely related genes SSX1 and SSX2 on chromosome X, The resulting chima eric genes express SYT-SSX1 or SYT-SSX2 fusion proteins in which the C -terminal amino acids of SYT are replaced by amino acids from the C-te rminus of the SSX proteins, Using green fluorescent protein fusions we demonstrate that the SYT, SSX and the SYT-SSX proteins are nuclear pr oteins,We demonstrate that whilst the SSX1 protein has a uniform nucle ar distribution the SYT protein has a speckled distribution in the cel l nucleus, and this distribution is retained with the SYT-SSX2 fusion protein, Since the SYT speckles do not co-localise with PML-containing bodies (PODs) or spliceosomes it is possible that they represent a no vel nuclear structure, Transfection of constructs expressing GAL4 fusi on proteins demonstrate that the SYT domains present in the SYT-SSX fu sion proteins can activate transcription of a luciferase reporter, It is proposed that the t(X;18) translocation results in the generation o f an SYT-SSX transcriptional co-activator in which the addition of the C-terminal SSX domain to SYT provides a new interacting domain that r edirects the SYT activation domain to different target promoters.