Document Detail


FOXO1 stimulates ceruloplasmin promoter activity in human hepatoma cells treated with IL-6.
MedLine Citation:
PMID:  21185807     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
FOXO1, a member of the winged-helix family of transcription factors, is a ubiquitously expressed protein involved in regulating a variety of cellular processes including glucose homeostasis, apoptosis, cell cycle control, muscle differentiation, and angiogenesis. In addition to these biological functions, FOXO1 is a key player in the oxidative stress response by stimulating the expression of metal-containing anti-oxidant proteins such as manganese superoxide dismutase, selenoprotein P, and catalase. Evidence in the literature suggests that FOXO1 may also be capable of regulating the expression of the anti-oxidant protein Ceruloplasmin (Cp), a six-copper-containing protein synthesized and secreted mainly by the liver. In the present report, we demonstrate that FOXO1 stimulates Cp promoter activity in conjunction with the cytokine IL-6. Through deletional analysis and in vitro binding studies, we determine the DNA sequence responsible for the FOXO1-dependent regulation of the Cp proximal promoter. Finally, we demonstrate that FOXO1 is capable of enhancing the expression of endogenous Cp in human hepatic carcinoma cells treated with IL-6. These results allow us to identify FOXO1 as a regulator of Cp expression to promote the anti-oxidant pathway in response to IL-6 signaling.
Authors:
Alpa Sidhu; Patrick J Miller; Andrew D Hollenbach
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Publication Detail:
Type:  Journal Article     Date:  2010-12-24
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  404     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  963-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, CSRB 6th floor, New Orleans, LA 70112, USA.
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