富含AU元件结合蛋白参与p38丝裂原活化蛋白激酶途径介导的mRNA稳定性调控。

The involvement of AU-rich element-binding proteins in p38 mitogen-activated protein kinase pathway-mediated mRNA stabilisation.

作者信息

Dean Jonathan L E, Sully Gareth, Clark Andrew R, Saklatvala Jeremy

机构信息

Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Rd, Hammersmith, London, W6 8LH, UK.

出版信息

Cell Signal. 2004 Oct;16(10):1113-21. doi: 10.1016/j.cellsig.2004.04.006.

DOI:10.1016/j.cellsig.2004.04.006

PMID:15240006

Abstract

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in the post-transcriptional regulation of inflammatory genes. p38 has been found to regulate both the translation and the stability of inflammatory mRNAs. The mRNAs regulated by p38 share common AU-rich elements (ARE) present in their 3'-untranslated regions. AREs act as mRNA instability determinants but also confer stabilisation of the mRNA by the p38 pathway. In recent years, AREs have shown to be binding sites for numerous proteins including HuR, TTP, AUF1, AUF2, FBP1, FBP2 (KSRP), TIA-1, and TIAR. However, it is unclear which protein is responsible for mRNA stabilisation by p38. This review gives an overview of the major ARE-binding proteins and discusses reasons for and against their involvement in p38-mediated mRNA stabilisation.

摘要

p38丝裂原活化蛋白激酶（MAPK）通路在炎症基因的转录后调控中发挥着重要作用。已发现p38可调节炎症mRNA的翻译和稳定性。受p38调节的mRNA在其3'非翻译区具有共同的富含AU元件（ARE）。ARE既是mRNA不稳定的决定因素，也可通过p38通路赋予mRNA稳定性。近年来，ARE已被证明是包括HuR、TTP、AUF1、AUF2、FBP1、FBP2（KSRP）、TIA-1和TIAR在内的多种蛋白质的结合位点。然而，尚不清楚哪种蛋白质负责p38介导的mRNA稳定性。本综述概述了主要的ARE结合蛋白，并讨论了支持和反对它们参与p38介导的mRNA稳定性的原因。