The synovial sarcoma-associated SYT-SSX2 oncogene antagonizes the polycomb complex protein Bmi1.

Abstract	This study demonstrates deregulation of polycomb activity by the synovial sarcoma-associated SYT-SSX2 oncogene, also known as SS18-SSX2. Synovial sarcoma is a soft tissue cancer associated with a recurrent t(X:18) translocation event that generates one of two fusion proteins, SYT-SSX1 or SYT-SSX2. The role of the translocation products in this disease is poorly understood. We present evidence that the SYT-SSX2 fusion protein interacts with the polycomb repressive complex and modulates its gene silencing activity. SYT-SSX2 causes destabilization of the polycomb subunit Bmi1, resulting in impairment of polycomb-associated histone H2A ubiquitination and reactivation of polycomb target genes. Silencing by polycomb complexes plays a vital role in numerous physiological processes. In recent years, numerous reports have implicated gain of polycomb silencing function in several cancers. This study provides evidence that, in the appropriate context, expression of the SYT-SSX2 oncogene leads to loss of polycomb function. It challenges the notion that cancer is solely associated with an increase in polycomb function and suggests that any imbalance in polycomb activity could drive the cell toward oncogenesis. These findings provide a mechanism by which the SYT-SSX2 chimera may contribute to synovial sarcoma pathogenesis.
Authors	Roy Barco, Christina B Garcia, Josiane E Eid
Journal	PloS one (PLoS One) Vol. 4 Issue 4 Pg. e5060 ( 2009) ISSN: 1932-6203 [Electronic] United States
PMID	19337376 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	BMI1 protein, human DNA Primers Histones Nuclear Proteins Oncogene Proteins, Fusion Proto-Oncogene Proteins Repressor Proteins SYT-SSX fusion protein Polycomb Repressive Complex 1
Topics	Base Sequence Cell Line, Tumor Chromatin Immunoprecipitation DNA Primers Fluorescent Antibody Technique, Indirect Histones (metabolism) Humans Nuclear Proteins (antagonists & inhibitors) Oncogene Proteins, Fusion (genetics) Polycomb Repressive Complex 1 Proto-Oncogene Proteins (antagonists & inhibitors) Repressor Proteins (antagonists & inhibitors) Reverse Transcriptase Polymerase Chain Reaction Sarcoma, Synovial (genetics) Ubiquitination

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