THOC5 couples M-CSF receptor signaling to transcription factor expression.
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/EBPbeta. Ectopic expression of THOC5 mimicked M-CSF mediated cell maturation and enhanced protein expression of the myeloid transcription factors C/EBPbeta, C/EBPalpha, 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 PtdInsP(3). Inhibition of THOC5-induced increases in PtdInsP(3) levels abrogated the elevated levels of C/EBPbeta. Thus THOC5 expression can potentiate receptor signalling to transcription factor expression and monocyte differentiation.
Carney
Louise
L
Stem Cell and Leukaemia Proteomics laboratory, Faculty of Medical and Human Sciences, University of Manchester, Christie Hospital, Wilmslow Road, Manchester M20 9BX, UK.
Pierce
Andrew
A
Rijnen
Marco
M
Gonzalez Sanchez
M Belen
MB
Hamzah
Hajja G
HG
Zhang
Liqun
L
Tamura
Teruko
T
Whetton
Anthony D
AD
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D022782:CCAAT-Enhancer-Binding Protein-beta; D009687:Nuclear Proteins; C530378:THOC5 protein, human; D014157:Transcription Factors; D016173:Macrophage Colony-Stimulating Factor; D019869:Phosphatidylinositol 3-Kinases; D016186:Receptor, Macrophage Colony-Stimulating Factor