PMID- 22328528 OWN - NLM STAT- MEDLINE DCOM- 20130124 LR - 20120528 IS - 1477-9137 (Electronic) IS - 0021-9533 (Linking) VI - 125 IP - Pt 8 DP - 2012 Apr 15 TI - Binding of the ERalpha and ARNT1 AF2 domains to exon 21 of the SRC1 isoform SRC1e is essential for estrogen- and dioxin-related transcription. PG - 2004-16 LID - 10.1242/jcs.097246 [doi] AB - 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-1alpha (HIF-1alpha), 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 ERalpha 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 ERalpha 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 ERalpha and ARNT1 AF2 domains in the C-terminus of SRC1e upregulates estrogen- and TCDD-related responses in mammalian cells. FAU - Endler, Alexander AU - Endler A AD - Department of Regenerative Medicine, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai 200092, China. alexanderendler@msn.com FAU - Chen, Li AU - Chen L FAU - Zhang, Jun AU - Zhang J FAU - Xu, Guo-Tong AU - Xu GT FAU - Shibasaki, Futoshi AU - Shibasaki F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120210 PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (ARNT protein, human) RN - 0 (Dioxins) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogens) RN - 0 (Protein Isoforms) RN - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) SB - IM MH - Aryl Hydrocarbon Receptor Nuclear Translocator/*chemistry/genetics/*metabolism MH - Dioxins/*metabolism MH - Estrogen Receptor alpha/genetics/*metabolism MH - Estrogens/*metabolism MH - Exons MH - Gene Expression Regulation MH - HeLa Cells MH - Humans MH - MCF-7 Cells MH - Nuclear Receptor Coactivator 1/*chemistry/genetics/*metabolism MH - Protein Binding MH - Protein Isoforms/chemistry/genetics/metabolism MH - Protein Structure, Tertiary MH - Transcription, Genetic MH - *Up-Regulation EDAT- 2012/02/14 06:00 MHDA- 2013/01/25 06:00 CRDT- 2012/02/14 06:00 PHST- 2012/02/14 06:00 [entrez] PHST- 2012/02/14 06:00 [pubmed] PHST- 2013/01/25 06:00 [medline] AID - jcs.097246 [pii] AID - 10.1242/jcs.097246 [doi] PST - ppublish SO - J Cell Sci. 2012 Apr 15;125(Pt 8):2004-16. doi: 10.1242/jcs.097246. Epub 2012 Feb 10.