Synovial sarcoma translocation (SYT) encodes a nuclear receptor coactivator

Endocrinology. 2005 Sep;146(9):3892-9. doi: 10.1210/en.2004-1513. Epub 2005 May 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • COS Cells
  • Chlorocebus aethiops
  • Gene Expression Regulation, Developmental
  • Histone Acetyltransferases
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivators
  • Protein Structure, Tertiary
  • RNA, Messenger / analysis
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Transcription Factors / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • NCOA6 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Nuclear Receptor Coactivators
  • RBM14 protein, human
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • synovial sarcoma X breakpoint proteins
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Nuclear Receptor Coactivator 1