[Frontiers in Bioscience 14, 847-871, January 1, 2009]

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

Andrew Clark, Jonathan Dean, Corina Tudor, Jeremy Saklatvala

Kennedy Institute of Rheumatology Division, Imperial College London, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Post-transcriptional regulation by MAPK pathways
3.1. p38 MAPK
3.2. ERK and JNK
3.3. MAPK signal-integrating kinases
4. Mediators of post-transcriptional regulation by MAPKs
4.1. Tristetraprolin
4.2. HuR
4.3. KSRP
4.4. The AUF family
4.5. Other mediators of post-transcriptional regulation by MAPKs
5. Summary and Perspective
6. Acknowledgements
7. References

1. ABSTRACT

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.