Hydrogen peroxide stimulates nuclear import of the POU homeodomain protein Oct-1 and its repressive effect on the expression of Cdx-2Report as inadecuate




Hydrogen peroxide stimulates nuclear import of the POU homeodomain protein Oct-1 and its repressive effect on the expression of Cdx-2 - Download this document for free, or read online. Document in PDF available to download.

BMC Cell Biology

, 11:56

First Online: 16 July 2010Received: 17 December 2009Accepted: 16 July 2010

Abstract

BackgroundThe ubiquitously expressed POU homeodomain protein Oct-1 serves as a sensor for stress induced by irradiation. We found recently that in pancreatic and intestinal endocrine cells, Oct-1 also functions as a sensor for cyclic AMP cAMP. The caudal homeobox gene Cdx-2 is a transactivator of proglucagon gcg and pro-insulin genes. Oct-1 binds to Cdx-2 promoter and represses its expression. cAMP elevation leads to increased nuclear exclusion of Oct-1, associated with reduced recruitment of nuclear co-repressors to the Cdx-2 promoter and increased Cdx-2 expression.

ResultsWe show in this study that inducing oxidative stress by hydrogen peroxide H2O2 increased nuclear Oct-1 content in both pancreatic α and β cell lines, as well as in a battery of other cells. This increase was then attributed to accelerated nuclear import of Oct-1, assessed by Fluorescence Recovery After Photobleaching FRAP using green fluorescence protein EGFP tagged Oct-1 molecule. H2O2 treatment was then shown to stimulate the activities of DNA-dependent protein kinase DNA-PK and c-jun N-terminal kinase JNK. Finally, increased Oct-1 nuclear content upon H2O2 treatment in a pancreatic α cell line was associated with reduced Cdx-2 and gcg mRNA expression.

ConclusionThese observations suggest that Oct-1 functions as a sensor for both metabolic and stress-survival signaling pathways via altering its nuclear-cytoplasmic shuttling.

AbbreviationsDNA-PKDNA-dependent protein kinase

EGFPenhanced green fluorescent protein

Epacexchange protein directly activated by cAMP

IBMX3-isobutyl-1-methylxanthine

JNKc-jun N-terminal kinase

MEKmitogen-activatedprotein kinase

OCToctamer-binding site

Oct-1octamer transcription factor-1

RTreverse transcription

H2O2hydrogen peroxide.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2121-11-56 contains supplementary material, which is available to authorized users.

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Author: Peixiang Wang - Tianru Jin

Source: https://link.springer.com/article/10.1186/1471-2121-11-56







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