Ultraviolet radiation (UVR) activates p38 MAP kinase and induces post-transcriptional stabilization of the C/EBPδ mRNA in G0 growth arrested mammary epithelial cells

Document Type

Article

Publication Date

4-1-2008

Abstract

The G0 growth arrest (quiescent) state is highly conserved in evolution to promote survival under adverse environmental conditions. To maintain viability, G0 growth arrested cells limit gene expression to essential growth control and pro-survival genes. CCAAT enhancer binding proteinδ (C/EBPδ), a member of the C/EBP family of nuclear proteins, is highly expressed in G0 growth arrested mammary epithelial cells (MECs). Although C/EBPδ gene transcription is elevated during G 0 growth arrest, C/EBPδ mRNA and protein are relatively short lived, suggesting tight control of the cellular C/EBPδ content in unstressed, quiescent cells. Treatment of G0 growth arrested MECs with ultraviolet radiation (UVR) dramatically increases the C/EBPδ mRNA half-life (∼4-fold) and protein content (∼3-fold). The mRNA stabilizing effects of UVR treatment are mediated by the C/EBPδ mRNA 3′untranslated region, which contains an AU rich element. UVR increased p38 MAP kinase (MAPK) activation and SB203580, a p38 MAPK inhibitor, blocked UVR-induced C/EBPδ mRNA stabilization. UVR increased the nuclear to cytoplasmic translocation of HuR, an ARE-binding protein that functions in mRNA stabilization. Finally, HuR siRNA treatment blocked UVR-induced stabilization of the C/EBPδ and C/EBPβ mRNAs but had no effect on C/EBPζ (CHOP) mRNA stability. In summary, G0 growth arrested MECs respond to UVR treatment by activating p38 MAPK, increasing HuR translocation and HuR/C/EBPδ mRNA binding and stabilizing the C/EBPδ mRNA. These results identify post-transcriptional stabilization of the C/EBPδ mRNA as a mechanism to increase C/EBPδ levels in the stress response of quiescent cells to UVR. © 2007 Wiley-Liss, Inc.

Publication Source (Journal or Book title)

Journal of Cellular Biochemistry

First Page

1657

Last Page

1669

This document is currently not available here.

Share

COinS