Binding of the ERα and ARNT1 AF2 domains to exon 21 of the SRC1 isoform SRC1e is essential for estrogen- and dioxin-related transcription

Journal of Cell Science
Alexander EndlerFutoshi Shibasaki

Abstract

Steroid receptor co-activator 1 (SRC1) is a transcriptional co-activator of numerous transcription factors involving nuclear receptors. Aryl hydrocarbon receptor nuclear translocator 1 (ARNT1) is an obligatory transcriptional partner of the aryl hydrocarbon receptor (AhR) and hypoxia inducible factor-1α (HIF-1α), as well as a co-activator of estrogen receptors (ERs). To initiate transcription, the activation function 2 (AF2) domains of estrogen-activated ERs interact with LxxLL motifs in the nuclear receptor interaction domain (NID) of SRC1. Here we describe an estrogen and LxxLL domain-independent ERα AF2 binding to SRC1e exon 21. In addition, we found an AF2 domain in exon 16 of ARNT1 that also binds to SRC1e exon 21. Surprisingly, the interaction between SRC1e exon 21 and the AF2 domain of ERα functions as a crucial enhancer of estrogen-induced transcription. The binding of ARNT1 AF2 to SRC1e exon 21 enhances the transcriptional response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but the upregulation essentially depends on two cyclin destruction boxes (D-boxes), which are also located on exon 16 of ARNT1. Our findings reveal that a binding site for ERα and ARNT1 AF2 domains in the C-terminus of SRC1e upregulates estrogen...Continue Reading

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Citations

Jun 21, 2014·International Journal of Molecular Sciences·Alexander EndlerFutoshi Shibasaki
Nov 5, 2014·Frontiers in Cell and Developmental Biology·Agnieszka Jablonska, Natalia Polouliakh
Aug 21, 2016·Molecular and Cellular Endocrinology·Ping GongBenita S Katzenellenbogen

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