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Title

A response unit in the first exon of the beta-amyloid precursor protein gene containing thyroid hormone receptor and Sp1 binding sites mediates negative regulation by 3,5,3'-triiodothyronine

AuthorsVilla, Ana; Santiago, Jorge; Belandia, Borja ; Pascual, Ángel
Issue DateApr-2004
PublisherEndocrine Society
CitationMolecular Endocrinology 18(4): 863-873 (2004)
AbstractThyroid hormones repress expression of APP (beta-amyloid precursor protein) in cultured cells of neuronal origin. The effect involves binding to the nuclear thyroid hormone receptor (TR) and is mediated by DNA sequences located within the first exon of the gene. These sequences contain a thyroid hormone response element that is necessary, but not sufficient, to mediate the inhibitory effect of the thyroid hormone T(3). In this report, we show that repression by T(3) is mediated by a response unit composed by the thyroid hormone response element and 5'-flanking sequences that bind Sp1 and mediate stimulation by this transcription factor. In that unit, binding sites for TR and Sp1 overlap and a complex mechanism appears to account for the TR-mediated regulation of APP. Unliganded TR does not bind to DNA and allows Sp1 to bind to DNA and stimulate APP basal expression. Binding of ligand T(3), which increases affinity of TR by DNA, precludes binding of Sp1 to DNA and decreases the Sp1-dependent expression of APP.
Description11 pages, 8 figures.
Publisher version (URL)http://dx.doi.org/10.1210/me.2003-0260
URIhttp://hdl.handle.net/10261/24581
DOI10.1210/me.2003-0260
ISSN0888-8809
Appears in Collections:(IIBM) Artículos
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