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

Maria Buxadé1, Nick Morrice2, Danielle L Krebs3

  • 1Division of Molecular Physiology and the Dundee DD1 5EH, United Kingdom; Department of Biochemistry & Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.

The Journal of Biological Chemistry
|October 30, 2007
PubMed

Insights

Researchers identified the PTB-associated splicing factor (PSF) as a novel substrate for MAP kinase signal-integrating kinases (Mnks). Mnk phosphorylation enhances PSF binding to tumor necrosis factor alpha mRNA, potentially regulating mRNA fate.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Proteomics

Background:

  • MAP kinase signal-integrating kinases (Mnks) interact with the translational machinery via the cap-binding initiation factor complex.
  • Identifying novel Mnk substrates is crucial for understanding kinase signaling pathways.

Purpose of the Study:

  • To identify new substrates of Mnks using a proteomic approach.
  • To investigate the functional consequence of Mnk phosphorylation on identified substrates.

Main Methods:

  • Proteomic analysis using cap resin to isolate interacting proteins.
  • In vitro kinase assays to test for Mnk phosphorylation.
  • In vivo studies to confirm substrate interaction and phosphorylation.
  • RNA immunoprecipitation assays to assess mRNA binding.

Main Results:

  • PTB-associated splicing factor (PSF) was identified as a novel Mnk substrate.
  • PSF is phosphorylated by Mnks at two sites both in vitro and in vivo.
  • PSF, along with p54(nrb), binds AU-rich element (ARE)-containing RNAs, including tumor necrosis factor alpha (TNFalpha) mRNA.
  • Mnk-mediated phosphorylation of PSF enhances its binding to TNFalpha mRNA.

Conclusions:

  • PSF is a novel substrate for Mnks.
  • Mnk-catalyzed phosphorylation of PSF regulates its binding to specific mRNAs like TNFalpha mRNA.
  • This phosphorylation may play a role in controlling the fate of inflammatory cytokine mRNAs.

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