Genomic collaboration of estrogen receptor α and extracellular signal-regulated kinase 2 in regulating gene and proliferation programs

Zeynep Madak-Erdogan, Mathieu Lupien, Fabio Stossi, Myles Brown, Benita S. Katzenellenbogen

Research output: Contribution to journalArticle

Abstract

The nuclear hormone receptor, estrogen receptor α (ERα), and mitogen-activated protein kinases (MAPKs) play key roles in hormone-dependent cancers, and yet their interplay and the integration of their signaling inputs remain poorly understood. In these studies, we document that estrogen-occupied ERα activates and interacts with extracellular signal-regulated kinase 2 (ERK2), a downstream effector in the MAPK pathway, resulting in ERK2 and ERα colocalization at chromatin binding sites across the genome of breast cancer cells. This genomic colocalization, predominantly at conserved distal enhancer sites, requires the activation of both ERα and ERK2 and enables ERK2 modulation of estrogen-dependent gene expression and proliferation programs. The ERK2 substrate CREB1 was also activated and recruited to ERK2-bound chromatin following estrogen treatment and found to cooperate with ERα/ERK2 in regulating gene transcription and cell cycle progression. Our study reveals a novel paradigm with convergence of ERK2 and ERα at the chromatin level that positions this kinase to support nuclear receptor activities in crucial and direct ways, a mode of collaboration likely to underlie MAPK regulation of gene expression by other nuclear receptors as well.

Original languageEnglish (US)
Pages (from-to)226-236
Number of pages11
JournalMolecular and cellular biology
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2011

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Mitogen-Activated Protein Kinase 1
Estrogen Receptors
Genes
Cytoplasmic and Nuclear Receptors
Mitogen-Activated Protein Kinases
Chromatin
Estrogens
cdc Genes
Gene Expression Regulation
Phosphotransferases
Binding Sites
Genome
Hormones
Breast Neoplasms
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Genomic collaboration of estrogen receptor α and extracellular signal-regulated kinase 2 in regulating gene and proliferation programs. / Madak-Erdogan, Zeynep; Lupien, Mathieu; Stossi, Fabio; Brown, Myles; Katzenellenbogen, Benita S.

In: Molecular and cellular biology, Vol. 31, No. 1, 01.01.2011, p. 226-236.

Research output: Contribution to journalArticle

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