• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


The transcriptional regulating protein of 132 kDa (TReP-132) enhances P450scc gene transcription through interaction with steroidogenic factor-1 in human adrenal cells.

The human P450scc gene is regulated by the tissue-specific orphan nuclear receptor, steroidogenic factor-1 (SF-1), which plays a key role in several physiologic processes including steroid synthesis, adrenal and gonadal development, and sexual differentiation. Several studies have demonstrated the interaction of SF-1 with different proteins. However, it is clear that additional factors not yet identified are involved with SF-1 to regulate different target genes. Recently, it was demonstrated that a novel transcriptional regulating protein of 132 kDa (TReP-132) regulates expression of the human P450scc gene. The overexpression of TReP-132 in adrenal cells increases the production of pregnenolone, which is associated with the activation of P450scc gene expression. Considering the colocalization of TReP-132 and SF-1 in steroidogenic tissues such as the adrenal and testis, and the presence of two putative LXXLL motifs in TReP-132 that can potentially interact with SF-1, the relationship between these two factors on the P450scc gene promoter was determined. The coexpression of SF-1 and TReP-132 in adrenal NCI-H295 cells cooperates to increase promoter activity. Pull-down experiments demonstrated the interaction between TReP-132 and SF-1, and this was further confirmed in intact cells by coimmunoprecipitation/Western blot and two-hybrid analyses. Deletions and mutations of the TReP-132 cDNA sequence demonstrate that SF-1 interaction requires the LXXLL motif found at the amino-terminal region of the protein. Also, the "proximal activation domain" and the "AF-2 hexamer" motif of SF-1 are involved in interaction with TReP-132. Consistent with previous studies showing interaction between CBP/p300 and SF-1 or TReP-132, the coexpression of these three proteins results in a synergistic effect on P450scc gene promoter activity. Taken together the results in this study identify a novel function of TReP-132 as a partner in a complex with SF-1 and CBP/p300 to regulate gene transcription involved in steroidogenesis.

Pubmed ID: 12101186


  • Gizard F
  • Lavallee B
  • DeWitte F
  • Teissier E
  • Staels B
  • Hum DW


The Journal of biological chemistry

Publication Data

October 18, 2002

Associated Grants


Mesh Terms

  • Adrenal Gland Neoplasms
  • Adrenal Glands
  • Amino Acid Motifs
  • Animals
  • Blotting, Western
  • Cholesterol Side-Chain Cleavage Enzyme
  • Chromatography, High Pressure Liquid
  • DNA, Complementary
  • DNA-Binding Proteins
  • E1A-Associated p300 Protein
  • Fushi Tarazu Transcription Factors
  • Glutathione Transferase
  • Homeodomain Proteins
  • Humans
  • Luciferases
  • Mice
  • Models, Genetic
  • Nuclear Proteins
  • Plasmids
  • Precipitin Tests
  • Pregnenolone
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Cytoplasmic and Nuclear
  • Steroidogenic Factor 1
  • Time Factors
  • Trans-Activators
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured