Selective regulation of type II interferon-inducible genes by NPM1/nucleophosmin

Nucleophosmin (NPM1) is a multifunctional nucleolar protein. Here, we analyze the role of NPM1 in gene expression using our previous microarray data and find a relationship between NPM1 and interferon (IFN)-gamma-inducible genes. We show that NPM1 selectively regulates the expression of a subset of IFN-gamma-inducible genes and directly binds to two important transcription factors in the type II IFN pathway: signal transducer and activator of transcription 1 and interferon regulatory factor 1 (IRF1). Furthermore, NPM1 is found to regulate the IFN-gamma-inducible promoter activity of major histocompatibility complex class II transactivator (CIITA), and mutation of the IRF1-binding site on the CIITA promoter abolishes the effect of NPM1. Our results suggest a novel mechanism for IFN-gamma-mediated gene expression by NPM1.