SSX1 Human

SSX1 is a fusion oncoprotein resulting from the chromosomal translocation t(X;18)(p11.2;q11.2), which fuses the SS18 gene on chromosome 18 to one of the SSX genes on the X chromosome. The most common fusion partners are SSX1 and SSX2. The resulting SS18-SSX1 fusion protein disrupts normal cellular functions by hijacking the BAF (BRG1/brm-associated factor) complex, a critical regulator of chromatin remodeling and gene expression .

The SS18-SSX1 fusion protein selectively recognizes H2AK119Ub nucleosomes, a specific form of ubiquitinated histone, through a unique cryptic groove formed by the H3 and Ub motif on the H2AK119 site . This interaction leads to the displacement of the BAF complex from promoters and enhancers to polycomb-repressed chromatin regions, thereby altering chromatin accessibility and gene expression . This mechanism is crucial for the oncogenic activity of SS18-SSX1 in synovial sarcoma.

Understanding the structure and function of SSX1 has significant implications for cancer research and therapy. The detailed cryo-EM structure of SSX1 bound to H2AK119Ub nucleosomes at 3.1 Å resolution has provided insights into its unique mode of ubiquitin recognition . This knowledge can potentially lead to the development of targeted therapies that disrupt the interaction between SS18-SSX1 and the BAF complex, thereby inhibiting the oncogenic activity of SSX1.

Recombinant SSX1 proteins are used in research to study the molecular mechanisms underlying synovial sarcoma and to develop potential therapeutic strategies. These recombinant proteins are produced using various expression systems and are essential tools for biochemical and cellular assays .