Feedback regulation of MAPK signalling by an RNA-binding protein
Feedback regulation of MAPK signalling by an RNA-binding protein
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DOI：
10.1038/nature01907
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发表时间：
2003-08
期刊：
影响因子：
64.8
通讯作者：
R. Sugiura;Ayako Kita;Y. Shimizu;H. Shuntoh;S. O. Sio;T. Kuno
中科院分区：
文献类型：
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作者：
R. Sugiura;Ayako Kita;Y. Shimizu;H. Shuntoh;S. O. Sio;T. Kuno
有丝分裂原活化蛋白激酶（MAPK）是进化上保守的酶，其将细胞外信号转化为各种输出，如细胞生长、分化和细胞死亡。MAPK磷酸酶通过使关键的磷酸苏氨酸和磷酸酪氨酸残基去磷酸化而选择性地抑制MAPK。MAPK磷酸酶表达的转录诱导由各种刺激，包括MAPK激活，已被充分证明为MAPK信号传导的负反馈机制。在这里，我们发现Rnc 1是裂殖酵母中一种新的K同源型RNA结合蛋白，它结合并稳定Pmp 1信使RNA，即Pmk 1的MAPK磷酸酶（参考文献，）。因此，Rnc 1作为Pmk 1信号传导的负调节剂。值得注意的是，Pmk 1磷酸化Rnc 1，导致Rnc 1的RNA结合活性增强。因此，Rnc 1是一个新的负反馈回路的组成部分，该回路通过与Pmp 1 mRNA的结合来调节Pmk 1通路。我们的发现-转录后的mRNA稳定的MAPK磷酸酶介导的RNA结合蛋白-提供了一个额外的调节机制，微调MAPK信号通路。
Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved enzymes that convert extracellular signals into various outputs such as cell growth, differentiation and cell death,,,. MAPK phosphatases selectively inactivate MAPKs by dephosphorylating critical phosphothreonine and phosphotyrosine residues,. The transcriptional induction of MAPK phosphatase expression by various stimuli, including MAPK activation, has been well documented as a negative-feedback mechanism of MAPK signalling,. Here we show that Rnc1, a novel K-homology-type RNA-binding protein in fission yeast, binds and stabilizes Pmp1 messenger RNA, the MAPK phosphatase for Pmk1 (refs , ). Rnc1 therefore acts as a negative regulator of Pmk1 signalling. Notably, Pmk1 phosphorylates Rnc1, causing enhancement of the RNA-binding activity of Rnc1. Thus, Rnc1 is a component of a new negative-feedback loop that regulates the Pmk1 pathway through its binding to Pmp1 mRNA. Our findings—the post-transcriptional mRNA stabilization of a MAPK phosphatase mediated by an RNA-binding protein—provide an additional regulatory mechanism for fine-tuning of MAPK signalling pathways.