Synovial Sarcoma, X Breakpoint 1 Human Recombinant
Synovial Sarcoma, X Breakpoint 2 Human Recombinant
Synovial sarcoma is a rare and aggressive form of soft tissue sarcoma that primarily affects adolescents and young adults. It is characterized by a specific chromosomal translocation, t(X;18)(p11.2;q11.2), which results in the fusion of the SS18 gene on chromosome 18 with one of the SSX genes (SSX1, SSX2, or SSX4) on the X chromosome . This fusion gene is a hallmark of synovial sarcoma and is used for diagnostic purposes .
Key Biological Properties: The SS18-SSX fusion protein disrupts normal cellular functions by altering gene expression and chromatin remodeling. It hijacks the BAF complex, a chromatin remodeling complex, and redirects it to polycomb-repressed regions, leading to changes in chromatin accessibility .
Expression Patterns: The SS18-SSX fusion protein is expressed in almost all cases of synovial sarcoma. It is not found in normal tissues, making it a specific marker for this type of cancer .
Tissue Distribution: Synovial sarcoma can occur in various soft tissues, but it is most commonly found near large joints such as the knee and ankle. It can also occur in the head and neck, mediastinum, and visceral organs like the lung and kidney .
Primary Biological Functions: The SS18-SSX fusion protein acts as an oncogene, driving the malignant transformation of cells. It alters transcriptional and epigenetic landscapes, leading to uncontrolled cell proliferation and tumor growth .
Role in Immune Responses and Pathogen Recognition: The SS18-SSX fusion protein can elicit immune responses, including both humoral and cellular immunity. This property has been explored for potential cancer immunotherapy strategies .
Mechanisms with Other Molecules and Cells: The SS18-SSX fusion protein interacts with various chromatin remodeling complexes, including the BAF complex and polycomb repressive complex. It selectively recognizes H2AK119Ub nucleosomes, leading to the displacement of the BAF complex from promoters and enhancers to polycomb-repressed regions .
Binding Partners and Downstream Signaling Cascades: The SS18-SSX fusion protein binds to specific histone modifications, such as H2AK119Ub, and induces DNA unwrapping at nucleosome entry/exit sites. This results in altered gene expression and contributes to the oncogenic properties of synovial sarcoma .
Transcriptional Regulation: The SS18-SSX fusion protein affects transcriptional regulation by interacting with transcription factors and chromatin remodeling complexes. It can repress or activate gene expression depending on the context .
Post-Translational Modifications: The activity of the SS18-SSX fusion protein is regulated by post-translational modifications, such as ubiquitination. These modifications can influence its binding affinity and interactions with other proteins .
Biomedical Research: The SS18-SSX fusion protein serves as a model for studying chromatin remodeling and gene regulation in cancer. It provides insights into the mechanisms of oncogenesis and potential therapeutic targets .
Diagnostic Tools: The presence of the SS18-SSX fusion gene is a diagnostic marker for synovial sarcoma. Molecular tests, such as fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR), are used to detect this fusion gene in clinical samples .
Therapeutic Strategies: Targeting the SS18-SSX fusion protein and its associated pathways is a promising therapeutic approach. Strategies include small molecule inhibitors, immunotherapy, and gene therapy .
Development to Aging and Disease: The SS18-SSX fusion protein plays a critical role in the development and progression of synovial sarcoma. It is involved in the early stages of tumor formation and continues to drive tumor growth and metastasis throughout the disease course . Understanding its role in different stages of the life cycle can help develop targeted therapies and improve patient outcomes.