Estrogen signaling multiple pathways to impact gene transcription

Maria Marino, Paola Galluzzo, Paolo Ascenzi

Research output: Contribution to journalArticle

Abstract

Steroid hormones exert profound effects on cell growth, development, differentiation, and homeostasis. Their effects are mediated through specific intracellular steroid receptors that act via multiple mechanisms. Among others, the action mechanism starting upon l7β-estradiol (E2) binds to its receptors (ER) is considered a paradigmatic example of how steroid hormones function. Ligand-activated ER dimerizes and translocates in the nucleus where it recognizes specific hormone response elements located in or near promoter DNA regions of target genes. Behind the classical genomic mechanism shared with other steroid hormones, E2 also modulates gene expression by a second indirect mechanism that involves the interaction of ER with other transcription factors which, in turn, bind their cognate DNA elements. In this case, ER modulates the activities of transcription factors such as the activator protein (AP)-1, nuclear factor-κB (NF-κB) and stimulating protein-1 (Sp-1), by stabilizing DNA-protein complexes and/ or recruiting co-activators. In addition, E2 binding to ER may also exert rapid actions that start with the activation of a variety of signal transduction pathways (e.g. ERK/MAPK, p38/MAPK, P13K/AKT, PLC/ PKC). The debate about the contribution of different ER-mediated signaling pathways to coordinate the expression of specific sets of genes is still open. This review will focus on the recent knowledge about the mechanism by which ERs regulate the expression of target genes and the emerging field of integration of membrane and nuclear receptor signaling, giving examples of the ways by which the genomic and non-genomic actions of ERs on target genes converge.

Original languageEnglish
Pages (from-to)497-508
Number of pages12
JournalCurrent Genomics
Volume7
Issue number8
DOIs
Publication statusPublished - Dec 2006

Fingerprint

Estrogens
Hormones
Steroids
Genes
DNA
Transcription Factors
Gene Expression
Steroid Receptors
Transcription Factor AP-1
Response Elements
p38 Mitogen-Activated Protein Kinases
Cytoplasmic and Nuclear Receptors
Growth and Development
Genetic Promoter Regions
Estradiol
Signal Transduction
Proteins
Homeostasis
Ligands
Membranes

Keywords

  • Estrogen
  • Estrogen receptors
  • Gene transcription
  • Genomic and non-genomic action mechanism

ASJC Scopus subject areas

  • Genetics

Cite this

Estrogen signaling multiple pathways to impact gene transcription. / Marino, Maria; Galluzzo, Paola; Ascenzi, Paolo.

In: Current Genomics, Vol. 7, No. 8, 12.2006, p. 497-508.

Research output: Contribution to journalArticle

Marino, Maria ; Galluzzo, Paola ; Ascenzi, Paolo. / Estrogen signaling multiple pathways to impact gene transcription. In: Current Genomics. 2006 ; Vol. 7, No. 8. pp. 497-508.
@article{9cdee02e09684c309df9da0585d68f4a,
title = "Estrogen signaling multiple pathways to impact gene transcription",
abstract = "Steroid hormones exert profound effects on cell growth, development, differentiation, and homeostasis. Their effects are mediated through specific intracellular steroid receptors that act via multiple mechanisms. Among others, the action mechanism starting upon l7β-estradiol (E2) binds to its receptors (ER) is considered a paradigmatic example of how steroid hormones function. Ligand-activated ER dimerizes and translocates in the nucleus where it recognizes specific hormone response elements located in or near promoter DNA regions of target genes. Behind the classical genomic mechanism shared with other steroid hormones, E2 also modulates gene expression by a second indirect mechanism that involves the interaction of ER with other transcription factors which, in turn, bind their cognate DNA elements. In this case, ER modulates the activities of transcription factors such as the activator protein (AP)-1, nuclear factor-κB (NF-κB) and stimulating protein-1 (Sp-1), by stabilizing DNA-protein complexes and/ or recruiting co-activators. In addition, E2 binding to ER may also exert rapid actions that start with the activation of a variety of signal transduction pathways (e.g. ERK/MAPK, p38/MAPK, P13K/AKT, PLC/ PKC). The debate about the contribution of different ER-mediated signaling pathways to coordinate the expression of specific sets of genes is still open. This review will focus on the recent knowledge about the mechanism by which ERs regulate the expression of target genes and the emerging field of integration of membrane and nuclear receptor signaling, giving examples of the ways by which the genomic and non-genomic actions of ERs on target genes converge.",
keywords = "Estrogen, Estrogen receptors, Gene transcription, Genomic and non-genomic action mechanism",
author = "Maria Marino and Paola Galluzzo and Paolo Ascenzi",
year = "2006",
month = "12",
doi = "10.2174/138920206779315737",
language = "English",
volume = "7",
pages = "497--508",
journal = "Current Genomics",
issn = "1389-2029",
publisher = "Bentham Science Publishers B.V.",
number = "8",

}

TY - JOUR

T1 - Estrogen signaling multiple pathways to impact gene transcription

AU - Marino, Maria

AU - Galluzzo, Paola

AU - Ascenzi, Paolo

PY - 2006/12

Y1 - 2006/12

N2 - Steroid hormones exert profound effects on cell growth, development, differentiation, and homeostasis. Their effects are mediated through specific intracellular steroid receptors that act via multiple mechanisms. Among others, the action mechanism starting upon l7β-estradiol (E2) binds to its receptors (ER) is considered a paradigmatic example of how steroid hormones function. Ligand-activated ER dimerizes and translocates in the nucleus where it recognizes specific hormone response elements located in or near promoter DNA regions of target genes. Behind the classical genomic mechanism shared with other steroid hormones, E2 also modulates gene expression by a second indirect mechanism that involves the interaction of ER with other transcription factors which, in turn, bind their cognate DNA elements. In this case, ER modulates the activities of transcription factors such as the activator protein (AP)-1, nuclear factor-κB (NF-κB) and stimulating protein-1 (Sp-1), by stabilizing DNA-protein complexes and/ or recruiting co-activators. In addition, E2 binding to ER may also exert rapid actions that start with the activation of a variety of signal transduction pathways (e.g. ERK/MAPK, p38/MAPK, P13K/AKT, PLC/ PKC). The debate about the contribution of different ER-mediated signaling pathways to coordinate the expression of specific sets of genes is still open. This review will focus on the recent knowledge about the mechanism by which ERs regulate the expression of target genes and the emerging field of integration of membrane and nuclear receptor signaling, giving examples of the ways by which the genomic and non-genomic actions of ERs on target genes converge.

AB - Steroid hormones exert profound effects on cell growth, development, differentiation, and homeostasis. Their effects are mediated through specific intracellular steroid receptors that act via multiple mechanisms. Among others, the action mechanism starting upon l7β-estradiol (E2) binds to its receptors (ER) is considered a paradigmatic example of how steroid hormones function. Ligand-activated ER dimerizes and translocates in the nucleus where it recognizes specific hormone response elements located in or near promoter DNA regions of target genes. Behind the classical genomic mechanism shared with other steroid hormones, E2 also modulates gene expression by a second indirect mechanism that involves the interaction of ER with other transcription factors which, in turn, bind their cognate DNA elements. In this case, ER modulates the activities of transcription factors such as the activator protein (AP)-1, nuclear factor-κB (NF-κB) and stimulating protein-1 (Sp-1), by stabilizing DNA-protein complexes and/ or recruiting co-activators. In addition, E2 binding to ER may also exert rapid actions that start with the activation of a variety of signal transduction pathways (e.g. ERK/MAPK, p38/MAPK, P13K/AKT, PLC/ PKC). The debate about the contribution of different ER-mediated signaling pathways to coordinate the expression of specific sets of genes is still open. This review will focus on the recent knowledge about the mechanism by which ERs regulate the expression of target genes and the emerging field of integration of membrane and nuclear receptor signaling, giving examples of the ways by which the genomic and non-genomic actions of ERs on target genes converge.

KW - Estrogen

KW - Estrogen receptors

KW - Gene transcription

KW - Genomic and non-genomic action mechanism

UR - http://www.scopus.com/inward/record.url?scp=33846066888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846066888&partnerID=8YFLogxK

U2 - 10.2174/138920206779315737

DO - 10.2174/138920206779315737

M3 - Article

C2 - 18369406

AN - SCOPUS:33846066888

VL - 7

SP - 497

EP - 508

JO - Current Genomics

JF - Current Genomics

SN - 1389-2029

IS - 8

ER -