JunD represses transcription and translation of the tight junction protein zona occludens-1 modulating intestinal epithelial barrier function.

Abstract:

:The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the TJ complex. Here, we show that JunD negatively regulates expression of ZO-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased JunD levels by ectopic overexpression of the junD gene or by depleting cellular polyamines repressed ZO-1 expression and increased epithelial paracellular permeability. JunD regulated ZO-1 expression at the levels of transcription and translation. Transcriptional repression of ZO-1 by JunD was mediated through cAMP response element-binding protein-binding site within its proximal region of the ZO-1-promoter, whereas induced JunD inhibited ZO-1 mRNA translation by enhancing the interaction of the ZO-1 3'-untranslated region with RNA-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that JunD is a biological suppressor of ZO-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function.

journal_name

Mol Biol Cell

authors

Chen J,Xiao L,Rao JN,Zou T,Liu L,Bellavance E,Gorospe M,Wang JY

doi

10.1091/mbc.e08-02-0175

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

3701-12

issue

9

eissn

1059-1524

issn

1939-4586

pii

E08-02-0175

journal_volume

19

pub_type

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