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Synovial Sarcoma Translocation (SYT) Encodes a Nuclear Receptor Coactivator

Discovery Biology Research and Clinical Investigation, Lilly Research Laboratories, Eli Lilly & Co. (T.I., W.W.C.), Indianapolis, Indiana 46285; Department of Integrative Physiology, Gunma University Graduate School of Medicine (T.I., N.K.), Maebashi, Gunma 371-8511, Japan; and Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corp. (T.I., N.K.), Kawaguchi, Saitama 332-0012, Japan

Address all correspondence and requests for reprints to: Dr. Toshiharu Iwasaki, Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Gunma, Japan. E-mail: tiwasaki{at}med.gunma-u.ac.jp.

We previously cloned and characterized a novel RNA-binding motif-containing coactivator, named coactivator activator (CoAA), as a thyroid hormone receptor-binding protein-interacting protein using a Sos-Ras yeast two-hybrid screening system. A database search revealed that CoAA is identical with synovial sarcoma translocation (SYT)-interacting protein. Thus, we hypothesized that SYT could also function as a coactivator. Subsequently, we isolated a cDNA encoding a larger isoform of SYT, SYT-long (SYT-L), from the brain and liver total RNA using RT-PCR. SYT-L possesses an additional 31 amino acids in its C terminus compared with SYT, suggesting that these two SYT isoforms may be expressed from two mRNAs produced by alternative splicing of a transcript from a single gene. By Northern blot analysis, we found that SYT-L mRNA is expressed in several human embryonic tissues, such as the brain, liver, and kidney. However, we could not detect SYT-L in adult tissues. Glutathione-S-transferase pull-down studies showed that SYT binds to the C-terminus of CoAA, but not to the coactivator modulator. Both isoforms of SYT function as transcriptional coactivators of nuclear hormone receptors in a ligand- and dose-dependent manner in CV-1, COS-1, and JEG-3 cells. However, the pattern of transactivation was different between SYT and SYT-L among these cells. SYT synergistically activates transcription with CoAA. In addition, SYT activates transcription through activator protein-1, suggesting that SYT may function as a general coactivator. These results indicate that SYT activates transcription, possibly through CoAA, to interact with the histone acetyltransferase complex.

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