Differential effect of IFN-alpha and IFN-gamma on phosphorylation of p65 and p50 (rel) in the K562 cell line: implications for altered interaction with RXR beta.

Phosphorylation of nuclear transcription factors plays an important role in their ability to regulate genes in a differential manner. Recent studies indicate that the rel homology domain mediates interaction of rel proteins with other transcription factors. The rel domain is multiply phosphorylated. Thus, altered phosphorylation in this domain would affect synergy of rel proteins with members of other transcription factor families. This could affect differential expression of genes that are regulated by a combination of the two transcription factors. We have observed that in the K562 cell line IFN-alpha treatment leads to deficient phosphorylation of nuclear p65/p50 (rel). We propose that this prevents interaction between p65/p50 and RXR beta in IFN-alpha treated K562 cells. This could be a major reason for the lack of globin gene transcription by IFN-alpha.