Cloning of an interferon regulatory factor 2 isoform with different regulatory ability

Interferons (IFNs) are a family of multifunctional proteins involved in imm une activation, regulation of cell growth and antiviral response. They exer t their functions by induction of several IFN-stimulated genes, including I FN regulatory factors (IRFs), a family of transcriptional regulators. One o f these factors, IRF-2, was initially cloned as an antagonistic counterpart to IRF-1 with oncogenic potential. Here we describe a second isoform of IR F-2, termed IRF-2s, cloned from human and murine cells. This isoform lacks two amino acids located C-terminal of the DNA-binding domain, which is cons erved in all IRF family members, leading to a change in the predicted secon dary structure. Both isoforms have similar binding affinities to known targ et sequences in electrophoretic mobility shift assays. Using reporter gene constructs with the type IV promoter region of the MHC class II transactiva tor (CIITA), which is the essential factor for IFN-gamma -induced MHC class II expression, we show that the short isoform IRF-2s exhibits a weaker act ivation ability compared to IRF-2. Thus, our data present the first evidenc e of two IRF-2 isoforms with different regulatory ability.