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Identification of a novel testicular orphan receptor-4 (TR4)-associated protein as repressor for the selective suppression of TR4-mediated transactivation.

Although many co-activators have been identified for various nuclear receptors, relatively fewer co-repressors have been isolated and characterized. Here we report the identification of a novel testicular orphan nuclear receptor-4 (TR4)-associated protein (TRA16) that is mainly localized in the nucleus of cells as a repressor to suppress TR4-mediated transactivation. The suppression of TR4-mediated transactivation is selective because TRA16 shows only a slight influence on the transactivation of androgen receptor, glucocorticoid receptor, and progesterone receptor. Sequence analysis shows that TRA16 is a novel gene with 139 amino acids in an open reading frame with a molecular mass of 16 kDa, which did not match any published gene sequences. Mammalian two-hybrid system and co-immunoprecipitation assays both demonstrate that TRA16 can interact strongly with TR4. The electrophoretic mobility shift assay suggests that TRA16 may suppress TR4-mediated transactivation via decreased binding between the TR4 protein and the TR4 response element on the target gene(s). Furthermore, TRA16 can also block the interaction between TR4 and TR4 ligand-binding domain through interacting with TR4-DNA-binding and ligand-binding domains. These unique suppression mechanisms suggest that TRA16 may function as a novel repressor to selectively suppress the TR4-mediated transactivation.

Pubmed ID: 12486131


  • Yang Y
  • Wang X
  • Dong T
  • Kim E
  • Lin WJ
  • Chang C


The Journal of biological chemistry

Publication Data

February 28, 2003

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK56784

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • COS Cells
  • Cell Nucleus
  • Cells, Cultured
  • DNA, Complementary
  • Gene Library
  • Genes, Reporter
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger
  • Receptors, Androgen
  • Receptors, Glucocorticoid
  • Receptors, Progesterone
  • Receptors, Steroid
  • Receptors, Thyroid Hormone
  • Repressor Proteins
  • Testis
  • Tissue Distribution
  • Transcriptional Activation
  • Transfection
  • Two-Hybrid System Techniques