A NOVEL INTERFERON REGULATORY FACTOR FAMILY TRANSCRIPTION FACTOR, ICSAT PIP/LSIRF, THAT NEGATIVELY REGULATES THE ACTIVITY OF INTERFERON-REGULATED GENES/

We have isolated a novel cDNA clone encoding interferon (IFN) consensu s sequence-binding protein in adult T-cell leukemia cell lines or acti vated T cells (ICSAT); this protein is the human homolog of the recent ly cloned Pip/LSIRF. ICSAT is structurally most closely related to the previously cloned ICSBP, a member of the IFN regulatory factor (IRF) family of proteins that binds to interferon consensus sequences (ICSs) found in many promoters of the IFN-regulated genes. Among T-cell line s investigated, ICSAT was abundantly expressed in human T-cell leukemi a virus type 1 (HTLV-1)-infected T cells. When the HTLV-1 tax gene was expressed or phorbol myristate acetate-A23187 stimulation was used, I CSAT expression was induced in Jurkat cells which otherwise do not exp ress ICSAT. When the binding of ICSAT to four different ICSs was teste d, the relative differences in binding affinities for those ICSs were determined. To study the functional role of ICSAT, we performed cotran sfection experiments with the human embryonal carcinoma cell line N-Te ra2. ICSAT was demonstrated to possess repressive function over the ge ne activation induced by IFN stimulation or by IRF-1 cotransfection. S uch repressive function is similar to that seen in IRF-2 or ICSBP. How ever, we have found that ICSAT has a different repressive effect from that of IRF-2 or ICSBP in some IFN-responsive reporter constructs. The se results suggest that a novel mechanism of gene regulation by ''diff erential repression'' is used by the multiple members of repressor pro teins with different repressive effects on the IFN-responsive genes.