Synovial sarcoma translocation (SYT) encodes a nuclear receptor coactivator

Area of Science:

• Molecular Biology
• Gene Regulation
• Cancer Biology

Background:

• Coactivator activator (CoAA) was identified as a thyroid hormone receptor-binding protein.
• CoAA shares identity with synovial sarcoma translocation (SYT)-interacting protein.
• This suggests SYT may also function as a coactivator.

Purpose of the Study:

• To investigate the coactivator function of SYT and its isoforms.
• To characterize the interaction between SYT and CoAA.
• To explore the role of SYT in transcriptional regulation.

Main Methods:

• Yeast two-hybrid screening to identify CoAA.
• RT-PCR to isolate SYT-long (SYT-L) cDNA.
• Northern blot analysis to determine SYT-L mRNA expression.
• Glutathione-S-transferase pull-down assays for protein interaction studies.
• Reporter gene assays in cell lines (CV-1, COS-1, JEG-3) to assess transcriptional activity.

Main Results:

• Identified SYT-L, a longer isoform of SYT, expressed in embryonic tissues but not adult tissues.
• Demonstrated that SYT binds to the C-terminus of CoAA.
• Both SYT and SYT-L act as transcriptional coactivators for nuclear hormone receptors in a ligand- and dose-dependent manner.
• SYT synergistically activates transcription with CoAA and through activator protein-1.
• SYT-L exhibits a different transactivation pattern compared to SYT across cell lines.

Conclusions:

• SYT and SYT-L function as transcriptional coactivators.
• SYT likely coactivates transcription through CoAA, potentially interacting with histone acetyltransferase complexes.
• SYT may act as a general coactivator, regulating transcription via multiple pathways.