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p120 nucleolar‐proliferating antigen is a direct target of G‐CSF signaling during myeloid differentiation
Author(s) -
KhannaGupta Arati,
Sun Hong,
Zibello Theresa,
Lozovatsky Larissa,
Ghosh Prabhat K.,
Link Daniel C.,
McLemore Morgan L.,
Berliner Nancy
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0205066
Subject(s) - biology , signal transduction , microbiology and biotechnology , stat5 , gene expression , bone marrow , gene , immunology , genetics
Granulocyte‐colony stimulating factor (G‐CSF) is an essential cytokine, which contributes to proliferation and differentiation of granulocyte precursor cells in the bone marrow. Despite recent progress in understanding G‐CSF signaling events, the mechanisms that underlie the distinct spectrum of biological functions attributed to G‐CSF‐mediated gene expression remain unclear. Previous studies have identified a number of genes, which are up‐regulated in G‐CSF‐stimulated myeloid precursor cells. In this study, we sought to identify additional target genes of G‐CSF‐mediated proliferation and/or differentiation. cDNA representational difference analysis was used with the 32Dcl3 cell line as a model system to isolate genes, which are up‐regulated in an immediate‐early manner upon G‐CSF stimualtion. We isolated p120 nucleolar‐proliferation antigen (NOL1), a highly conserved, nucleolar‐specific, RNA‐binding protein of unknown function, and confirmed its expression by Northern blot analysis in 4‐h, G‐CSF‐induced 32Dcl3 cells. Isolation of a mouse p120 genomic clone revealed the presence of a signal tranducer and activator of transcription (STAT)‐binding site in the first intron of the gene. We demonstrate the importance of STAT3 and STAT5 in mediating the G‐CSF response with respect to p120 expression by transient transfection analysis, oligonucleotide pull‐down assays, and the loss of p120 expression in the bone marrow of mice lacking normal STAT3 signaling. In addition, overexpression of p120 in G‐CSF‐induced 32D cells revealed normal, morphologic maturation and growth characteristics but loss of lactoferrin expression, a marker of normal neutrophil maturation, suggesting that inappropriate expression of the p120 gene can result in aberrant neutrophil maturation.