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

Maria Buxadé, Nick Morrice, Danielle L. Krebs, Christopher G. Proud

    Research output: Contribution to journalArticlepeer-review

    62 Citations (Scopus)

    Abstract

    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, p54(nrb), binds RNAs that contain AU-rich elements (AREs), such as those for proinflammatory cytokines (e.g. tumor necrosis factor alpha (TNFalpha)). Indeed, PSF associates specifically with the TNFalpha 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 TNFalpha 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.p54(nrb).
    Original languageEnglish
    Pages (from-to)57-65
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume283
    Issue number1
    DOIs
    Publication statusPublished - 2008

    Keywords

    • 3' Untranslated Regions
    • Cell Line
    • Chromatography, Affinity
    • Electrophoresis, Polyacrylamide Gel
    • Humans
    • Immunoblotting
    • Immunoprecipitation
    • Jurkat Cells
    • Nuclear Matrix-Associated Proteins
    • Octamer Transcription Factors
    • Phosphorylation
    • Protein Binding
    • Protein-Serine-Threonine Kinases
    • RNA, Messenger
    • RNA-Binding Proteins
    • Reverse Transcriptase Polymerase Chain Reaction
    • Substrate Specificity
    • Transfection
    • Tumor Necrosis Factor-alpha

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