Role of the transcription factor PU.1 in the regulation of lipopolysaccharide-inducible genes

Studies were performed to evaluate the role of the Ets transcription factor PU.1 in the regulation of gene activation by Gram-negative bacterial lipopolysaccharide (LPS). These studies revealed that LPS activation of the murine macrophage cell line RAW264.7 led to the rapid phosphorylation of PU.1 at serine residues. Functional studies revealed that LPS-induced phosphorylation of PU.1 at serine 148 increased the trans-activation function of PU.1. This serine is a known site for phosphorylation by protein kinase CK2 (Casein Kinase II). Furthermore, phosphorylation of PU.1 correlated with the activation of CK2 kinase activity following LPS stimulation. These studies show that LPS stimulation leads to the activation of CK2, the phosphorylation of PU.1, and the enhancement of PU.1 trans-activation function. The role of PU.1 in the regulation of HIV-1 gene expression was also investigated. LPS-inducible HIV-1 gene expression is mediated, in part, by binding of the transcription factor NF-...