A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated with ISG15.
Interferon (IFN) regulates various target genes that mediate important roles in immune responses such as antiviral state. Protein ISG15-conjugation (ISGylation) is implicated in the IFN-induced antiviral response. Here we demonstrate that Efp mRNA as well as protein expression could be up-regulated by Type I IFN in HeLa cells and HepG2 cells. Luciferase assay reveals that the first intron of Efp gene contains a functional interferon-stimulated response element (ISRE) and electrophoretic mobility shift assay shows that the ISRE binds to signal transducer and activator of transcription 1 (STAT1). Chromatin immunoprecipitation assays have shown that the ISRE recruits STAT1 in vivo IFN-dependently. Moreover, we demonstrate that Efp protein could be conjugated with not only ubiquitin but also ISG15. These data suggest that Efp is an IFN-responsive gene that potentially mediates IFN actions, involved in ISGylation and ubiquitination of proteins including Efp itself.
Nakasato
Norie
N
Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Ikeda
Kazuhiro
K
Urano
Tomohiko
T
Horie-Inoue
Kuniko
K
Takeda
Satoru
S
Inoue
Satoshi
S
D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology / Q000502:physiology*; D007438:Introns; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D016207:Cytokines; D007370:Interferon Type I; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D014452:Ubiquitins; C074034:ISG15 protein, human; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases