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 language | English |
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Pages (from-to) | 309-316 |
Number of pages | 7 |
Journal | Cell. Signal. |
Volume | 21 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2009 |
Keywords
- THOC5
- C/EBP beta
- PI3Kinase
- Differentiation
- Monocyte
- Spliceosome