COUP-TF and transcriptional co-regulators in adrenal steroidogenesis

Hirotaka Shibata, Sakiko Kobayashi, Isao Kurihara, Noriko Suda, Kenichi Yokota, Ayano Murai, Yayoi Ikeda, Ikuo Saito, William E. Rainey, Takao Saruta

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Chicken ovalbumin upstream promoter-transcription factors (COUP-TFs) and steroidogenic factor-1 (SF-1) play key roles in the transcriptional regulation of steroidogenic P450 genes. Transfection studies showed that SF-1 activated bovine CYP17 promoter activity, whereas COUP-TFs repressed it from the CRS2 element in a mutually exclusive manner in mouse adrenocortical Y-1 cells. COUP-TFI and SF-1 competitively bind to the Ad5 element of the human CYP11B2 gene promoter. Unexpectedly, overexpression of COUP-TFI increased the CYP11B2 promoter activity, whereas overexpression of SF-1 repressed it in human adrenocortical H295R cells. In cortisol-producing adrenal cortical adenomas, down-regulation of nuclear receptors, including COUP-TFs was found. We therefore screened for COUP-TFI-interacting proteins using a yeast two-hybrid system and have identified Ubc9 and PIAS1, SUMO-1 conjugating enzyme and ligase, respectively. Coexpression of Ubc9 and PIAS1 synergistically enhanced COUP-TFI-mediated transrepression of CYP17 gene as well as transactivation of CYP11B2 gene. The SUMOylation-defective mutants of these proteins continued to function as co-regulators of COUP-TFI. These findings indicate that Ubc9 and PIAS1 can function as transcriptional co-regulators of COUP-TFI to modulate adrenal cortical steroidogenesis in a SUMOylation-independent manner.

Original languageEnglish
Pages (from-to)795-801
Number of pages7
JournalEndocrine Research
Volume30
Issue number4
DOIs
Publication statusPublished - 2004 Dec 1

Keywords

  • COUP-TFI
  • Co-activator
  • Co-repressor
  • PIASI
  • SUMO
  • Ubc9

ASJC Scopus subject areas

  • Endocrinology

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  • Cite this

    Shibata, H., Kobayashi, S., Kurihara, I., Suda, N., Yokota, K., Murai, A., Ikeda, Y., Saito, I., Rainey, W. E., & Saruta, T. (2004). COUP-TF and transcriptional co-regulators in adrenal steroidogenesis. Endocrine Research, 30(4), 795-801. https://doi.org/10.1081/ERC-200044042