Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 23, Issue 9, Pages 1628-1635Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E11-05-0412
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Funding
- National Science Foundation of China [30900732, 31100979, 81030046, 31171112]
- National Key Basic Research and Development Program [2009CB521704]
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Differentiated macrophages are essential for the innate immune system; however, the molecular mechanisms underlying the generation of macrophages remain largely unknown. Here we show that the RNA-binding protein QKI, mainly QKI-5, is transcriptionally activated in the early differentiated monocytic progenitors when CCAAT/enhancer-binding protein (C/EBP) alpha is expressed. The forced expression of C/EBP alpha increases the endogenous expression of QKI. Chromatin immunoprecipitation analysis and reporter assays further confirm that C/EBP alpha activates the transcription of QKI, primarily by binding to the distal C/EBP alpha-binding site. Blocking the induction of QKI using RNA interference enhances the expression of endogenous CSF1R and facilitates macrophage differentiation. Further study of the mechanism reveals that QKI-5 facilitates the degradation of CSF1R mRNA by interacting with the distal QRE in the 3' untranslated region. In summary, we show that in committed macrophage progenitors, C/EBP alpha-activated QKI-5 negatively regulates macrophage differentiation by down-regulating CSF1R expression, forming a negative feedback loop during macrophage differentiation.
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