COUP-TF and transcriptional co-regulators in adrenal steroidogenesis

Hirotaka Shibata, Sakiko Kobayashi, Isao Kurihara, Noriko Suda, Kenichi Yokota, Ayano Takeda, 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

Fingerprint

COUP Transcription Factors
Steroidogenic Factor 1
Cytochrome P-450 CYP11B2
Steroid 17-alpha-Hydroxylase
Sumoylation
COUP Transcription Factor I
Genes
Adrenocortical Adenoma
Two-Hybrid System Techniques
Mutant Proteins
Ligases
Cytoplasmic and Nuclear Receptors
Transcriptional Activation
Transfection
Hydrocortisone
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Endocrinology

Cite this

COUP-TF and transcriptional co-regulators in adrenal steroidogenesis. / Shibata, Hirotaka; Kobayashi, Sakiko; Kurihara, Isao; Suda, Noriko; Yokota, Kenichi; Takeda, Ayano; Ikeda, Yayoi; Saito, Ikuo; Rainey, William E.; Saruta, Takao.

In: Endocrine Research, Vol. 30, No. 4, 2004, p. 795-801.

Research output: Contribution to journalArticle

Shibata, H, Kobayashi, S, Kurihara, I, Suda, N, Yokota, K, Takeda, A, Ikeda, Y, Saito, I, Rainey, WE & Saruta, T 2004, 'COUP-TF and transcriptional co-regulators in adrenal steroidogenesis', Endocrine Research, vol. 30, no. 4, pp. 795-801. https://doi.org/10.1081/ERC-200044042
Shibata, Hirotaka ; Kobayashi, Sakiko ; Kurihara, Isao ; Suda, Noriko ; Yokota, Kenichi ; Takeda, Ayano ; Ikeda, Yayoi ; Saito, Ikuo ; Rainey, William E. ; Saruta, Takao. / COUP-TF and transcriptional co-regulators in adrenal steroidogenesis. In: Endocrine Research. 2004 ; Vol. 30, No. 4. pp. 795-801.
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