ICSBP/IRF-8 transactivation: a tale of protein-protein interaction

Interferon (IFN) consensus sequence binding protein (ICSBP) is a member of a family of transcription factors termed IFN regulatory factors (IRF) and is also called IRF-8. Its expression is restricted mainly to cells of the immune system, and it plays a key role in the maturation of macrophages. ICSBP exerts its activity through the formation of different DNA-binding heterocomplexes. The interacting partner dictates a specific DNA recognition sequence, thus rendering ICSBP dual transcriptional activity, that is, repression or activation. Accordingly, such DNA elements were identified at the promoter regions of target genes that manifest macrophage action. A specific module (IRF association domain [IAD]) within ICSBP and a PEST domain located on the interacting partners mediate this association. Thus, ICSBP serves as an excellent prototype, demonstrating how a small subset of transcription factors can regulate gene expression in a spatial, temporal, and delicate tuning through combinatorial protein-protein interactions on different enhanceasomes.