Synovial sarcoma translocation (SYT) encodes a nuclear receptor coactivator.
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.
Iwasaki
Toshiharu
T
Discovery Biology Research and Clinical Investigation, Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 46285, USA. tiwasaki@med.gunma-u.ac.jp
Koibuchi
Noriyuki
N
Chin
William W
WW
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D056918:Nuclear Receptor Coactivators; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; C436317:RBM14 protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C093962:synovial sarcoma X breakpoint proteins; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1