Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus

Thaete, C., Brett, D., Monaghan, P., Whitehouse, S., Rennie, G., Rayner, E., Cooper, C. S. ORCID: https://orcid.org/0000-0003-2013-8042 and Goodwin, G. (1999) Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus. Human Molecular Genetics, 8 (4). pp. 585-591. ISSN 0964-6906

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Abstract

The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Here we have investigated the functional domains of the proteins. The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species, and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences. Deletion of the SNH domain results in a more active transcriptional activator, suggesting that this domain acts as an inhibitor of the activation domain. The C-terminal SSX domain present in SYT-SSX translocation protein contributes a transcriptional repressor domain to the protein. Thus, the fusion protein has transcriptional activating and repressing domains. We demonstrate that the human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with SYT and SYT-SSX proteins in vitro. This interaction may provide an explanation of how the SYT protein activates gene transcription.

Item Type: Article
Uncontrolled Keywords: molecular biology,genetics,genetics(clinical) ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
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Depositing User: LivePure Connector
Date Deposited: 18 Jul 2022 16:30
Last Modified: 23 Oct 2022 04:01
URI: https://ueaeprints.uea.ac.uk/id/eprint/86492
DOI: 10.1093/hmg/8.4.585

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