The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor α

被引:66
作者
Buxade, Maria [1 ,3 ]
Morrice, Nick [2 ]
Krebs, Danielle L. [3 ]
Proud, Christopher G. [1 ,3 ]
机构
[1] Univ Dundee, Coll Life Sci, Div Mol Physiol, Dundee DD1 5EH, Scotland
[2] Univ Dundee, Coll Life Sci, Med Res Council Protein Phosphorylat Unit, Dundee DD1 5EH, Scotland
[3] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada
关键词
D O I
10.1074/jbc.M705286200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To identify new potential substrates for the MAP kinase signal-integrating kinases (Mnks), we employed a proteomic approach. The Mnks are targeted to the translational machinery through their interaction with the cap-binding initiation factor complex. Wetested whether proteins retained on cap resin were substrates for the Mnks in vitro, and identified one such protein as PSF (the PTB (polypyrimidine tract-binding protein)-associated splicing factor). Mnks phosphorylate PSF at two sites in vitro, and our data show that PSF is an Mnk substrate in vivo. We also demonstrate that PSF, together with its partner, p54(nrb), binds RNAs that contain AU-rich elements (AREs), such as those for proinflammatory cytokines (e. g. tumor necrosis factor alpha (TNF alpha)). Indeed, PSF associates specifically with the TNF alpha mRNA in living cells. PSF is phosphorylated at two sites by the Mnks. Our data show that Mnk-mediated phosphorylation increases the binding of PSF to the TNF alpha mRNA in living cells. These findings identify a novel Mnk substrate. They also suggest that the Mnk-catalyzed phosphorylation of PSF may regulate the fate of specific mRNAs by modulating their binding to PSF.p54nrb.
引用
收藏
页码:57 / 65
页数:9
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