FOXO1 stimulates ceruloplasmin promoter activity in human hepatoma cells treated with IL-6

Alpa Sidhu; Patrick J Miller; Andrew D Hollenbach

doi:10.1016/j.bbrc.2010.12.089

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FOXO1 stimulates ceruloplasmin promoter activity in human hepatoma cells treated with IL-6

Journal article

Peer reviewed

FOXO1 stimulates ceruloplasmin promoter activity in human hepatoma cells treated with IL-6

Alpa Sidhu, Patrick J Miller and Andrew D Hollenbach

Biochemical and biophysical research communications, Vol.404(4), pp.963-967

01/28/2011

DOI: 10.1016/j.bbrc.2010.12.089

PMID: 21185807

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Abstract

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.

Ceruloplasmin - genetics

Interleukin-6 - pharmacology

Signal Transduction

Forkhead Transcription Factors - metabolism

Humans

Gene Expression Regulation

Cell Line, Tumor

Forkhead Box Protein O1

Forkhead Transcription Factors - genetics

Promoter Regions, Genetic - drug effects

Interleukin-6 - metabolism

Details

Title: Subtitle: FOXO1 stimulates ceruloplasmin promoter activity in human hepatoma cells treated with IL-6
Creators: Alpa Sidhu - Department of Genetics, Louisiana State University Health Sciences Center, 533 Bolivar Street, CSRB 6th floor, New Orleans, LA 70112, USA
Patrick J Miller
Andrew D Hollenbach
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.404(4), pp.963-967
DOI: 10.1016/j.bbrc.2010.12.089
PMID: 21185807
ISSN: 0006-291X
eISSN: 1090-2104
Grant note: 1-P20-RR020152-01 / NCRR NIH HHS P20 RR020152 / NCRR NIH HHS
Language: English
Date published: 01/28/2011
Academic Unit: Stead Family Department of Pediatrics; Medical Genetics and Genomics
Record Identifier: 9984093229202771

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