Sugiura Reiko, Satoh Ryosuke, Ishiwata Shunji, Umeda Nanae, Kita Ayako
Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan.
J Signal Transduct. 2011;2011:109746. doi: 10.1155/2011/109746. Epub 2011 Apr 5.
Mitogen-activated protein kinases (MAPKs), which are found in all eukaryotes, are signal transducing enzymes playing a central role in diverse biological processes, such as cell proliferation, sexual differentiation, and apoptosis. The MAPK signaling pathway plays a key role in the regulation of gene expression through the phosphorylation of transcription factors. Recent studies have identified several RNA-binding proteins (RBPs) as regulators of MAPK signaling because these RBPs bind to the mRNAs encoding the components of the MAPK pathway and regulate the stability of their transcripts. Moreover, RBPs also serve as targets of MAPKs because MAPK phosphorylate and regulate the ability of RBPs to bind and stabilize target mRNAs, thus controlling various cellular functions. In this review, we present evidence for the significance of the MAPK signaling in the regulation of RBPs and their target mRNAs, which provides additional information about the regulatory mechanism underlying gene expression. We further present evidence for the clinical importance of the posttranscriptional regulation of mRNA stability and its implications for drug discovery.
丝裂原活化蛋白激酶(MAPKs)存在于所有真核生物中,是信号转导酶,在多种生物学过程中发挥核心作用,如细胞增殖、性别分化和细胞凋亡。MAPK信号通路通过转录因子的磷酸化在基因表达调控中起关键作用。最近的研究已确定几种RNA结合蛋白(RBPs)为MAPK信号的调节因子,因为这些RBPs与编码MAPK通路组分的mRNA结合并调节其转录本的稳定性。此外,RBPs也是MAPKs的作用靶点,因为MAPKs使RBPs磷酸化并调节其结合和稳定靶mRNA的能力,从而控制各种细胞功能。在本综述中,我们提供证据证明MAPK信号在调节RBPs及其靶mRNA中的重要性,这为基因表达的潜在调控机制提供了更多信息。我们还进一步提供证据证明mRNA稳定性的转录后调控在临床上的重要性及其对药物发现的意义。