期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 103, 期 5, 页码 1657-1669出版社
WILEY
DOI: 10.1002/jcb.21554
关键词
ultraviolet radiation (UVR); CCAAT/enhancer binding protein delta; C/EBP delta; mRNA stability; p38 mitogen; activated kinase (MAPK) post-transcriptional regulation; G(0) growth arrest
资金
- NCI NIH HHS [CA57607, P30 CA16058] Funding Source: Medline
The Go 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 protein delta (C/EBP delta), a member of the C/EBP family of nuclear proteins, is highly expressed in Go growth arrested mammary epithelial cells (MECs). Although C/EBP delta gene transcription is elevated during G(0) growth arrest, C/EBP delta mRNA and protein are relatively short lived, suggesting tight control of the cellular C/EBP delta content in unstressed, quiescent cells. Treatment of G(0) growth arrested MECs with ultraviolet radiation (UVR) dramatically increases the C/EBP delta mRNA half-life (similar to 4-fold) and protein content (similar to 3-fold). The mRNA stabilizing effects of UVR treatment are mediated by the C/EBP delta 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/EBP delta 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/EBP delta and C/EBP beta mRNAs but had no effect on C/EBP (CHOP) mRNA stability. In summary, Go growth arrested MECs respond to UVR treatment by activating p38 MAPK, increasing HuR translocation and HuR/C/EBP delta rnRNA binding and stabilizing the C/EBP delta mRNA. These results identify post-transcriptional stabilization of the C/EBP delta mRNA as a mechanism to increase C/EBP delta levels in the stress response of quiescent cells to UVR.
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