A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen.

A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen. Research Abstract Details 

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A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen. Abstract Text:

Jingwei Cheng,Chen Zhang,David J Shapiro,

To evaluate the contribution of ERK1/2 phosphorylation of estrogen receptor (ER)-alpha to activation and repression of endogenous genes, we produced stably transfected lines of HeLa cells with functional ERK1/2 pathways that express similar levels of wild-type human ERalpha and ERalpha mutated to inactivate the well-known MAPK site at serine 118 (ERalphaS118A). We compared effects of the S118A mutation on 17beta-estradiol (E(2))-mediated transactivation, which is heavily dependent on activation function (AF) 2 of ERalpha and on 4-hydroxytamoxifen (OHT)-mediated transactivation, which is heavily dependent on AF1, which includes S118. To examine whether S118 was the key ERK/MAPK phosphorylation site in ERalpha action, we compared the effects of the S118A mutant and the ERK inhibitor U0126 on expression of endogenous genes. In several estrogen response element-containing genes, the S118A mutation strongly reduced induction by E(2), and U0126 did not further reduce expression. Expression of another group of estrogen response element-containing genes was largely unaffected by the S118A mutation. The S118A mutation had variable effects on genes induced by ER tethering or binding near specificity protein-1 and activator protein-1 sites. For five mRNAs whose expression is strongly down-regulated by E(2) and partially or completely down-regulated by OHT, the S118A mutation reduced or abolished down-regulation by E(2) and nearly abolished down-regulation by OHT. In contrast, for Sma and mothers against decapentaplegic-3-related, which is down-regulated by E(2) and not OHT, the S118A mutation had little effect. These data suggest that there may be distinct groups of genes down-regulated by ERalpha and suggest a novel role for ERK phosphorylation at serine 118 in AF1 in regulating expression of the set of genes down-regulated by OHT.

A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen. Publishing Authors By Initials

J Cheng,C Zhang,DJ Shapiro,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Endocrinology

VOLUME: 148

Page Numbers: 4634-41

Journal Abbreviation: Endocrinology

ISSN: 0013-7227

DAY: 5

MONTH: 07

YEAR: 2007

A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen. Information

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LANGUAGE: eng

NlmUniqueID: 375040

A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: pharmacology

Chemical & Substance for Abstract: A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen. Information

Substance Name: Extracellular Signal-Regulated MAP Kinas

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for A functional serine 118 phosphorylation site in estrogen receptor-alpha is required for down-regulation of gene expression by 17beta-estradiol and 4-hydroxytamoxifen.

AFFILIATION: Department of Biochemistry, University of Illinois, 600 South Mathews, Urbana, IL 61801, USA.

Country: United States

AGENCY: United States NICHD

GRANT: HD 16720

ACRONYM: HD

MEDLINETA: Endocrinology

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