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

14 Citations (Scopus)

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

Fingerprint

Steroidogenic Factor 1
Steroid 17-alpha-Hydroxylase
Transcription Factor AP-1
Cytoplasmic and Nuclear Receptors
Protein Kinase C
Zona Glomerulosa
Angiotensin II
Enzyme Inhibitors
Ovary
Down-Regulation
Steroids
Gene Expression
Genes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Sirianni, R., Nogueira, E., Bassett, M. H., Carr, B. R., Suzuki, T., Pezzi, V., ... 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

The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1. / Sirianni, Rosa; Nogueira, Edson; Bassett, Mary H.; Carr, Bruce R.; Suzuki, Takashi; Pezzi, Vincenzo; Andò, Sebastiano; Rainey, William E.

In: Journal of Cell Science, Vol. 123, No. 22, 15.11.2010, p. 3956-3965.

Research output: Contribution to journalArticle

Sirianni, R, Nogueira, E, Bassett, MH, Carr, BR, Suzuki, T, Pezzi, V, Andò, S & Rainey, WE 2010, 'The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1', Journal of Cell Science, vol. 123, no. 22, pp. 3956-3965. https://doi.org/10.1242/jcs.055806
Sirianni, Rosa ; Nogueira, Edson ; Bassett, Mary H. ; Carr, Bruce R. ; Suzuki, Takashi ; Pezzi, Vincenzo ; Andò, Sebastiano ; Rainey, William E. / The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1. In: Journal of Cell Science. 2010 ; Vol. 123, No. 22. pp. 3956-3965.
@article{b52265546c34409883640f52f19cc1a6,
title = "The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1",
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.",
keywords = "Adrenal, AP-1, CYP17, SF-1",
author = "Rosa Sirianni and Edson Nogueira and Bassett, {Mary H.} and Carr, {Bruce R.} and Takashi Suzuki and Vincenzo Pezzi and Sebastiano And{\`o} and Rainey, {William E.}",
year = "2010",
month = "11",
day = "15",
doi = "10.1242/jcs.055806",
language = "English (US)",
volume = "123",
pages = "3956--3965",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "22",

}

TY - JOUR

T1 - The AP-1 family member FOS blocks transcriptional activity of the nuclear receptor steroidogenic factor 1

AU - Sirianni, Rosa

AU - Nogueira, Edson

AU - Bassett, Mary H.

AU - Carr, Bruce R.

AU - Suzuki, Takashi

AU - Pezzi, Vincenzo

AU - Andò, Sebastiano

AU - Rainey, William E.

PY - 2010/11/15

Y1 - 2010/11/15

N2 - 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.

AB - 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.

KW - Adrenal

KW - AP-1

KW - CYP17

KW - SF-1

UR - http://www.scopus.com/inward/record.url?scp=78649740261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649740261&partnerID=8YFLogxK

U2 - 10.1242/jcs.055806

DO - 10.1242/jcs.055806

M3 - Article

VL - 123

SP - 3956

EP - 3965

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 22

ER -