Post-transcriptional gene regulation by MAP kinases via AU-rich elements

Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK.
Frontiers in Bioscience (Impact Factor: 3.52). 02/2009; 14:847-71.
Source: PubMed


Eukaryotic cells must continuously sense their environments, for example their attachment to extracellular matrix and proximity to other cells, differences in temperature or redox conditions, the presence of nutrients, growth factors, hormones, cytokines or pathogens. The information must then be integrated and an appropriate response initiated by modulating the cellular programme of gene expression. The mitogen-activated protein kinase (MAPK) signaling pathways play a critical role in this process. Decades of research have illuminated the many ways in which MAPKs regulate the synthesis of mRNA (transcription) via phosphorylation of transcription factors, cofactors, and other proteins. In recent years it has become increasingly clear that the control of mRNA destruction is equally important for cellular responses to extracellular cues, and is equally subject to regulation by MAPKs. This review will summarize our current understanding of post-transcriptional regulation of gene expression by the MAPKs and the proteins that are involved in this process.

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    • "It has been reported that adenosine-uracil multimers known as AU-rich element (ARE) in the 3′-untranslated region (3′-UTR) plays an important role in the post-transcriptional regulation of TNF-α mRNA [13] [14]. The regulation of mRNA stability is mediated by ARE-binding proteins, which interact with ARE and promote/suppress mRNA decay [15] [16] [17]. "
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    • "Only combined JNK1/2-deficient cells and not the single knockout cell, exhibit a severe defect in Tnfα mRNA expression [45, 47], suggesting redundant actions of JNK1 and JNK2 in TNF regulation. Although some reports suggest that JNK could also be involved in post-translational regulation of cytokines, direct mechanistic links between JNK and mRNA stability or translation remain elusive [48]. "
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    • "In addition, these data may provide the framework for a new avenue for exploring the cross-talking between the MAPK and NF-κB signaling pathways, both of which are involved in downstream signaling following TLR stimulation. Activation of MAPK signaling has been well-documented to regulate RNA turnover and protein stability of inflammatory effector molecules through post-transcriptional mechanisms [37], [38]. Such activities of MAPK signaling are involved in the regulation of NF-κB-mediated inflammatory responses [27], [38]. "
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