THOC5 couples M-CSF receptor signaling to transcription factor expression

Louise Carney, Andrew Pierce, Marco Rijnen, M. Belen Gonzalez Sanchez, Hajja G. Hamzah, Liqun Zhang, Teruko Tamura, Anthony D. Whetton

    Research output: Contribution to journalArticlepeer-review

    Abstract

    THOC5 is a nuclear/cytoplasmic protein member of the spliceosome complex which potentiates C/EBP expression in adipocyte differentiation. As C/EBP family members are important regulators of myelopoiesis and THOC5 is highly expressed in neutrophil/macrophage progenitor cells we assessed the role of THOC5 in cytokine-stimulated monocytic development. M-CSF stimulated maturation of the NFS60 cell line was associated with enhanced THOC5 expression and phosphorylation. THOC5 was also shown to form a complex with C/EBPβ. Ectopic expression of THOC5 mimicked M-CSF mediated cell maturation and enhanced protein expression of the myeloid transcription factors C/EBPβ, C/EBPα, Pu-1 and also GAB2 (a PI-3 Kinase and macrophage development regulator). Increased THOC5 expression also mimicked M-CSF stimulated increases in the lipid second messenger PtdInsP3. Inhibition of THOC5-induced increases in PtdInsP3 levels abrogated the elevated levels of C/EBPβ. Thus THOC5 expression can potentiate receptor signalling to transcription factor expression and monocyte differentiation. © 2008 Elsevier Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)309-316
    Number of pages7
    JournalCell. Signal.
    Volume21
    Issue number2
    DOIs
    Publication statusPublished - Feb 2009

    Keywords

    • THOC5
    • C/EBP beta
    • PI3Kinase
    • Differentiation
    • Monocyte
    • Spliceosome

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