CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP

Article Article scientifique Article CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP eng 2010 author Carascossa Sophie 642196 author Dudek Peter author Cenni Bruno author Briand Pierre-André author Picard Didier 0000-0001-8816-9668 26830 708-719 10.1101/gad.568410 0890-9369 http://genesdev.cshlp.org/content/24/7/708.full The estrogen receptor α (ERα) is activated as a transcription factor by both estrogen and a large variety of other extracellular signals. The mechanisms of this ligand-independent activation, notably by cAMP signaling, are still largely unknown. We now close the gap in the signaling pathway between cAMP and ERα. Whereas the direct phosphorylation of ERα by the cAMP-activated protein kinase A (PKA) is dispensable, the phosphorylation of the coactivator-associated arginine methyltransferase 1 (CARM1) by PKA at a single serine is necessary and sufficient for direct binding to the unliganded hormone-binding domain (HBD) of ERα, and the interaction is necessary for cAMP activation of ERα. Sustained PKA activity promoting a constitutive interaction may contribute to tamoxifen resistance of breast tumors. Binding and activation involve a novel regulatory groove of the ERα HBD. As a result, depending on the activating signal, ERα recruits different coactivator complexes to regulate alternate sets of target genes. Steroid receptor Signaling Coactivator Protein kinase A Breast cancer Endocrine resistance Dewey 570 46 Département de biologie cellulaire 165 false Genes & development 24 7 7f521449-bd6a-433f-9d4a-64c03d4dc666 Article (Accepted version) Restricted Carascossa_G&D.pdf 6120004 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de biologie cellulaire

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CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP	Genes & development			2010	630	0

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Carascossa, Sophie