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Mol Cell Biol. 2007 Feb;27(4):1321-33. Epub 2006 Nov 27.

Suppression of beta-amyloid precursor protein signaling into the nucleus by estrogens mediated through complex formation between the estrogen receptor and Fe65.

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1
Department of Pathology, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612-4799, USA.

Abstract

The C-terminal fragment of the beta-amyloid precursor protein produced after cleavage by gamma-secretase, namely, APPct or AICD, has been shown to form a multimeric complex with the adaptor protein Fe65 and to regulate transcription through the recruitment of the histone acetyltransferase Tip60. The present study shows that 17beta-estradiol inhibits the transcriptional and apoptotic activities of the APPct complex by a process involving the interaction of estrogen receptor alpha (ERalpha) with Fe65. ERalpha-Fe65 complexes were detected both in vitro and in the mouse brain, and recruitment of ERalpha to the promoter of an APPct target gene (KAI1) was demonstrated. Our studies reveal a novel mechanism of estrogen action, which may explain the well-known neuroprotective functions of estrogens as well as the complex role of this female hormone in the pathogenesis of neuronal degeneration diseases.

PMID:
17130235
PMCID:
PMC1800721
DOI:
10.1128/MCB.01280-06
[Indexed for MEDLINE]
Free PMC Article
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