title: Phosphorylation events modulate the ability of interferon consensus sequence binding protein to interact with interferon regulatory factors and to bind DNA.
abstract: Two families of transcription factors mediate interferon (IFN) signaling. The first family, signal transducers and activators of transcription (STATs), is activated within minutes of IFN treatment. Specific phosphorylation events lead to their translocation to the nucleus, formation of transcriptional complexes, and the induction of the second family of transcription factors termed interferon regulatory factors (IRFs). Interferon consensus sequence binding protein (ICSBP) is a member of IRF family that is expressed only in cells of the immune system and acts as a transcriptional repressor. ICSBP binds DNA through the association with other transcription factors such as IRF-1 or IRF-2. In this communication, the domain that is involved in protein-protein interactions was mapped to the carboxyl terminus of ICSBP. This domain is also important for mediating ICSBP-repressing activity. In vitro studies demonstrated that direct binding of ICSBP to DNA is prevented by tyrosine (Tyr) phosphorylation. Yet, Tyr-phosphorylated ICSBP can bind target DNA only through the association with IRF-2 and IRF-1. This type of phosphorylation is essential for the formation of heterocomplexes. Tyr-phosphorylated ICSBP and IRF-2 are detected in expressing cells constitutively, and Tyr-phosphorylated IRF-1 is induced by IFN-gamma. These results strongly suggest that like the STATs, the IRFs are also modulated by Tyr phosphorylation that affects their biological activities.
authors.affiliation: Department of Food Engineering and Biotechnology, Technion, Haifa 32000, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Sharf
authors.forename: D
authors.initials: D
authors.lastname: Meraro
authors.forename: A
authors.initials: A
authors.lastname: Azriel
authors.forename: A M
authors.initials: AM
authors.lastname: Thornton
authors.forename: K
authors.initials: K
authors.lastname: Ozato
authors.forename: E F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: A C
authors.initials: AC
authors.lastname: Larner
authors.forename: F
authors.initials: F
authors.lastname: Schaper
authors.forename: H
authors.initials: H
authors.lastname: Hauser
authors.forename: B Z
authors.initials: BZ
authors.lastname: Levi
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050835:Interferon Regulatory Factors; D007372:Interferons / Q000378:metabolism*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
chemical_list: D002352:Carrier Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D050835:Interferon Regulatory Factors; D007372:Interferons; D010750:Phosphoproteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014443:Tyrosine; D000099185:Interferon Regulatory Factor-8; C494257:IRF1 protein, human; C494229:IRF2 protein, human