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

Buxade, Maria, Morrice, Nick, Proud, Christopher G. and Krebs, Danielle L. (2008) The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha. Journal of Biological Chemistry, 283, (1), 57-65. (doi:10.1074/jbc.M705286200). (PMID:17965020).


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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. We tested 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, p54nrb, binds RNAs that contain AU-rich elements (AREs), such as those for proinflammatory cytokines (e.g. tumor necrosis factor ? (TNF?)). Indeed, PSF associates specifically with the TNF? 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? 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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1074/jbc.M705286200
ISSNs: 0021-9258 (print)
1083-351X (electronic)
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions : University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 159295
Accepted Date and Publication Date:
4 January 2008Published
26 October 2007Made publicly available
Date Deposited: 30 Jun 2010 10:03
Last Modified: 31 Mar 2016 13:27

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