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EnglishIn the present study, the molecular mechanism underlying the up-regulatory effect of estradiol (E-2) on mouse insulin receptor substrate-1 (IRS-1) promoter was investigated in CHO cells on which the same promoter had first been functionally characterized. The mouse IRS-1 promoter bears four consensus half Estrogen Responsive Elements (ERE) sequences and thirteen AP-1- and ten Sp1-binding elements. We performed molecular dissection of this promoter gene providing 3' different deleted constructs, containing the same AP-1 rich region with a progressively increased number of ERE half sites located downstream. None of these constructs was responsive to E-2 while a downstream region (nt -1420 to -160) rich in GC elements was induced by E-2. However, the latter region lost its intrinsic E-2 responsiveness when the whole IRS-1 promoter was mutated for deletion in all four ERE half sites. Deletion analysis of the ERE half sites demonstrated that only ERE located at the position -1500 to -1495, close to the GC-rich region, was able to maintain the induced activatory effect of E-2 on the IRS-1 gene. Electrophoretic mobility shift and chromatin immunoprecipitation assays identified the region containing the half ERE/Sp1 (nt -1500 to -1477) as the one conferring E2 responsiveness to the whole promoter. This effect occurs through the functional interaction between E-2/ER alpha. and Sp1.
Evidence that the mouse insulin receptor substrate-1 belongs to the gene family on which the promoter is activated by estrogen receptor alpha through its interaction with Sp1 / Panno, Maria Luisa; Mauro, Loredana; Marsico, Stefania; Bellizzi, Dina; Rizza, P; Morelli, C; Salerno, M; Giordano, Francesca; Ando', Sebastiano. - In: JOURNAL OF MOLECULAR ENDOCRINOLOGY. - ISSN 0952-5041. - 36:1(2006), pp. 91-105.
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| Titolo: | Evidence that the mouse insulin receptor substrate-1 belongs to the gene family on which the promoter is activated by estrogen receptor alpha through its interaction with Sp1 |
| Autori: | |
| Data di pubblicazione: | 2006 |
| Rivista: | |
| Citazione: | Evidence that the mouse insulin receptor substrate-1 belongs to the gene family on which the promoter is activated by estrogen receptor alpha through its interaction with Sp1 / Panno, Maria Luisa; Mauro, Loredana; Marsico, Stefania; Bellizzi, Dina; Rizza, P; Morelli, C; Salerno, M; Giordano, Francesca; Ando', Sebastiano. - In: JOURNAL OF MOLECULAR ENDOCRINOLOGY. - ISSN 0952-5041. - 36:1(2006), pp. 91-105. |
| Handle: | http://hdl.handle.net/20.500.11770/122719 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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