Oestradiol induction of a glucocorticoid-responsive gene by a chimaeric receptor

Green, Stephen; Chambon, Pierre

doi:10.1038/325075a0

Cited by 430 publications

(138 citation statements)

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“…Progesterone and glucocorticoid receptors bind to the same sequences with subtle differences that can influence the relative strength of binding to different sites (Chalepakis et al, 1988). The more diverged estrogen receptor has a distinct specificity (Green and Chambon, 1987). Other examples of regulators with overlapping sequence specificity include members of the Jun-Ap1 family (Struhl, 1987;Franza et al, 1988) and a number of CAAT binding proteins (Jones et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

The sequence specificity of homeodomain-DNA interaction

Desplan¹,

Theis

O’Farrell

1988

Cell

483

332

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SummaryThe Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity. Using deletion constructs expressed as fusion proteins in E. coli, we localized this activity to the conserved homeodomain (HD). The binding site consensus, TCAATTAAAT, is found in clusters in the engrailed regulatory region. Weak binding of the En HD to one copy of a synthetic consensus is enhanced by adjacent copies. The distantly related HD encoded by fushi tarazu binds to the same sites as the En HD, but differs in its preference for related sites. Both HDs bind a second type of sequence, a repeat of TAA. The similarity in sequence specificity of En and Ftz HDs suggests that, within families of DNA binding proteins, close relatives will exhibit similar specificities. Competition among related regulatory proteins might govern which protein occupies a given binding site and consequently determine the ultimate effect of cis-acting regulatory sites.

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Section: Discussionmentioning

confidence: 99%

The sequence specificity of homeodomain-DNA interaction

Desplan¹,

Theis

O’Farrell

1988

Cell

483

332

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“…Both COS7 and HEK293 cells were transfected with expression plasmids for human ER␣. The data presented in this study were obtained with the expression plasmid HE0 (34). This plasmid contains the human wild-type ER␣ cDNA-clone OR8 as described in Ref.…”

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confidence: 99%

Estrogen Receptor α Rapidly Activates the IGF-1 Receptor Pathway

Kahlert¹,

Nuedling²,

Eickels³

et al. 2000

Journal of Biological Chemistry

429

297

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Estrogen and insulin-like-growth factor 1 (IGF-1) are potent mitogenic stimuli that share important properties in the control of cellular proliferation. However, the coupling between the signaling cascades of estrogen receptors ␣ and ␤ and the IGF-1 receptor (IGF-1R) is poorly understood. Therefore, we selectively transfected estrogen receptor ␣ or ␤ in COS7 and HEK293 cells, which contain IGF-1R. In presence of estrogen receptor ␣ but not ␤, 17␤-estradiol (E2) rapidly induces phosphorylation of the IGF-1R and the extracellular signal-regulated kinases 1/2. Furthermore, upon stimulation with E2, estrogen receptor ␣ but not ␤ bound rapidly to the IGF-1R in COS7 as well as L6 cells, which express all investigated receptors endogenously. Control experiments in the IGF-1R-deficient fibroblast cell line R ؊ showed that after stimulation with E2 only estrogen receptor ␣ bound to the transfected IGF-1R. Overexpression of dominant negative mitogen-activated protein kinases kinase inhibited this effect. Finally, estrogen receptor ␣ but not ␤ is required to induce the activation of the estrogen receptor-responsive reporter ERE-LUC in IGF-1-stimulated cells. Taken together, these data demonstrate that ligand bound estrogen receptor ␣ is required for rapid activation of the IGF-1R signaling cascade.Estrogen as well as insulin-like growth factor 1 (IGF-1) 1 are potent mitogens that are involved in a large array of processes that control proliferation and differentiation in mammalian cells (1, 2). Both mitogens act through receptor-mediated signaling pathways. The cross-talk between these two signaling pathways is currently under investigation (3-6). Estrogen is a steroid hormone that binds to members of the nuclear receptor superfamily (7), whereas IGF-1 as a peptide-growth factor binds to a transmembrane tyrosine kinase receptor, which signals via a series of phosphorylation events (2).Two different estrogen receptors, ER␣ and ER␤, which are encoded by genes located on different chromosomes, have been identified so far (8,9). Sequence analysis demonstrates a high degree of homology between ER␣ and ER␤ in the DNA-binding domain and the ligand-binding domain. However, there are significant differences in regions that would be expected to influence transcriptional activity. The ability of estrogen receptors to activate target gene transcription has been attributed to two regions: the N-terminal activation function 1 (AF-1) and the ligand-dependent AF-2, which is localized in the C-terminal hormone-binding domain (10, 11). AF-1 and AF-2 can activate transcription independently and synergistically, and they act in a promoter-and cell-specific manner (12, 13). Phosphorylation of a serine residue at position 118 is required for full action of the AF-1 (14). Both AF-1 and AF-2 are required to enhance transcription of target genes through AP-1 sites (15). Interestingly, ER␣ and ER␤ act differently at AP-1 sites (16), which may be due to differences in their AF domains (17). ER␣ and ER␤ can form homo-and heterodimers (18), and thus t...

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“…18 In a now classical experiment, the glucocorticoid HRE became responsive to ␤-estradiol by replacing the C region of ER with that of GR. 19 Region E, the ligand-binding domain, is also involved in other structurally overlapping functions, [20][21][22][23][24] including transactivation 22 and dimerization. 23,24 The receptor polarity of DR HREs, with RXR at the 5′ HRE half-site, plus the freedom of rotation about the hinge region of the 3′-dimeric partner, 25 suggests the ligandbinding domains of RAR, VDR, and TR may be functionally interchangeable.…”

Section: Introductionmentioning

confidence: 99%