Cloning of an interferon regulatory factor 2 isoform with different regulatory ability.
Interferons (IFNs) are a family of multifunctional proteins involved in immune activation, regulation of cell growth and antiviral response. They exert their functions by induction of several IFN-stimulated genes, including IFN regulatory factors (IRFs), a family of transcriptional regulators. One of these factors, IRF-2, was initially cloned as an antagonistic counterpart to IRF-1 with oncogenic potential. Here we describe a second isoform of IRF-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 conserved in all IRF family members, leading to a change in the predicted secondary structure. Both isoforms have similar binding affinities to known target sequences in electrophoretic mobility shift assays. Using reporter gene constructs with the type IV promoter region of the MHC class II transactivator (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 activation ability compared to IRF-2. Thus, our data present the first evidence of two IRF-2 isoforms with different regulatory ability.
Koenig Merediz
S A
SA
Abteilung für Molekularbiologie, Biochemie und Bioinformatik, Fachbereich Humanmedizin, Freie Universität Berlin, 14195 Berlin, Germany.
Schmidt
M
M
Hoppe
G J
GJ
Alfken
J
J
Meraro
D
D
Levi
B Z
BZ
Neubauer
A
A
Wittig
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005802:Genes, MHC Class II / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D050836:Interferon Regulatory Factor-2; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; C494230:Irf2 protein, mouse; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA