Ultraviolet radiation (UVR) activates p38 MAP kinase and induces post-transcriptional stabilization of the C/EBPδ mRNA in G0 growth arrested mammary epithelial cells
✍ Scribed by Bin Li; Junling Si; James W. DeWille
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 358 KB
- Volume
- 103
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
The G~0~ growth arrest (quiescent) state is highly conserved in evolution to promote survival under adverse environmental conditions. To maintain viability, G~0~ 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 G~0~ 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 G~0~ 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, G~0~ 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. J. Cell. Biochem. 103: 1657–1669, 2008. © 2007 Wiley‐Liss, Inc.