Interferon regulatory factor family of transcription factors and regulation of oncogenesis

Abstract

A family of transcription factors, the interferon regulatory factors (IRF), was identified originally in the context of the regulation of the type I interferon (IFN)-alpha/beta system. The IRF family has now expanded to nine members, and gene-disruption studies have revealed the critical involvement of these members in multiple facets of host defense systems, such as innate and adaptive immune responses and tumor suppression. In the present review article, we aim at summarizing our current knowledge of the roles of IRF in host defense, with special emphasis on their involvement in the regulation of oncogenesis.

Figure 1

Interferon regulatory factor (IRF) family members. The fundamental characteristics of the nine human IRF family members (IRF1 to IRF9) and one avian IRF10 are shown in the table (left), and their schematic domain models are shown in the right panel. All IRF carry the N‐terminal DNA‐binding domain (DBD), which contains repeated tryptophan residues (represented by ‘W’) similar to c‐myb. All IRF, except IRF1 and IRF2, have an IRF association domain (IAD1) that is responsible for interaction with other family members or transcription factors such as PU.1, E47, and Stat. Another association domain (IAD2) that is present in IRF1 and IRF2 is important for their interaction with IRF8. Mammalian IRF10 has not been reported. Among the four viral IRF (vIRF) encoded by human herpesvirus‐8, vIRF1 is shown as a representative. vIRF1 also contains an IAD domain.

Figure 2

Mutations and aberrant expression of interferon regulatory factor (IRF) genes in human cancers. (a) Schematic representation of human chromosomes and gene loci of IRF genes. (b) Summary table of previous reports about mutations and aberrant expression of the IRF genes in primary specimens derived from human malignancies. Expression levels included are based on both mRNA and protein levels. AML, acute myelogenous leukemia; ALL, acute lymphocytic leukemia; CML, chronic myelogenous leukemia; NSCLC, non‐small cell lung cancer; CNS, central nervous system; t‐AML, therapy‐related acute myelogenous leukemia.