The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1

Rosa Sirianni, Edson Nogueira, Mary H. Bassett, Bruce R. Carr, Takashi Suzuki, Vincenzo Pezzi, Sebastiano Andò, William E. Rainey

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Steroid production in the adrenal zona glomerulosa is under the control of angiotensin II (Ang II), which, upon binding to its receptor, activates protein kinase C (PKC) within these cells. PKC is a potent inhibitor of the steroidogenic enzyme CYP17. We have demonstrated that, in the ovary, PKC activates expression of FOS, a member of the AP-1 family, and increased expression of this gene is linked to CYP17 downregulation. However, the pathway and the molecular mechanism responsible for the inhibitory effect of PKC on CYP17 expression are not defined. Herein, we demonstrated that Ang II inhibited CYP17 through PKC and ERK1/2-activated FOS and that blocking FOS expression decreased PKC-mediated inhibition. Although CYP17 transcription was activated by the nuclear receptor SF-1, expression of FOS resulted in a decrease in SF-1-mediated gene transcription. FOS physically interacted with the hinge region of SF-1 and modulated its transactivity, thus preventing binding of cofactors such as SRC1 and CBP, which were necessary to fully activate CYP17 transcription. Collectively, these results indicate a new regulatory mechanism for SF-1 transcriptional activity that might influence adrenal zone-specific expression of CYP17, a mechanism that can potentially be applied to other steroidogenic tissues.

Original languageEnglish (US)
Pages (from-to)3956-3965
Number of pages10
JournalJournal of cell science
Volume123
Issue number22
DOIs
StatePublished - Nov 15 2010

Keywords

  • AP-1
  • Adrenal
  • CYP17
  • SF-1

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1'. Together they form a unique fingerprint.

  • Cite this

    Sirianni, R., Nogueira, E., Bassett, M. H., Carr, B. R., Suzuki, T., Pezzi, V., Andò, S., & Rainey, W. E. (2010). The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1. Journal of cell science, 123(22), 3956-3965. https://doi.org/10.1242/jcs.055806