Interferon Regulatory Factor 7 Is Activated by a Viral Oncoprotein through RIP-Dependent Ubiquitination

Huye, Leslie E.; Ning, Shunbin; Kelliher, Michelle A.; Pagano, Joseph S.

doi:10.1128/mcb.02256-06

Cited by 76 publications

(105 citation statements)

References 49 publications

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“…6). However, RIP1 was critical for LMP1-induced IRF7 activation, as assayed by ISREdependent promoter responses (data not shown) and previously reported (20).…”

Section: Irf7 Amino Acids 194 -411 Bind Strongly To Ctar2 and Block Irf7mentioning

confidence: 91%

“…Because LMP1 activation of IRF7 is RIP1 dependent and is associated with both RIP1 and IRF7 K63-linked polyubiquitination (20), we investigated the potential role of RIP1 in LMP1 association with IRF7. LMP1 associated with IRF7 in WT mouse embryonic fibroblasts (MEFs) and at least as well with IRF7 in RIP1 knock out (KO) MEFs, indicating that RIP1 does not mediate IRF7 association with LMP1 (Fig.…”

Section: Irf7 Amino Acids 194 -411 Bind Strongly To Ctar2 and Block Irf7mentioning

confidence: 99%

“…Because LMP1 induces IRF7 and RIP1 K63-linked polyubiquitination (20), the role of TRAF2, TRAF3, or TRAF6 K63 E3-ubiqutin ligases in IRF7 activation was investigated. LMP1 activated IRF7 equally well in WT and TRAF2 or TRAF3 KO MEFs (Fig.…”

Section: Irf7 Amino Acids 194 -411 Bind Strongly To Ctar2 and Block Irf7mentioning

confidence: 99%

“…Because the same MyD88 residues affect IRF7 binding and activation, the importance of IRF7 binding for activation has been difficult to assess (30). LMP1 residues that activate IRF7 have not been identified (20). We therefore investigated the LMP1 residues required for IRF7 activation, assessed whether IRF7 binding to these residues is critical for activation, and evaluated the role of RIP1, TRAF2, TRAF3, and TRAF6 in IRF7 activation.…”

mentioning

confidence: 99%

“…LMP1 also induces and activates IFN regulatory factor 7 (IRF7) (18)(19)(20), a critical transcription factor for type 1 IFN (IFN)-mediated innate and adaptive immune responses (21)(22)(23)(24). IRF7 is comprised of DNA binding, constitutive activation, virus activated, inhibitory, and signal response domains and is activated by serine 477 and 479 phosphorylation (25).…”

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confidence: 99%

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IRF7 activation by Epstein–Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3

Song

Izumi

Shinners

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1), a constitutively aggregated and activated pseudoreceptor, activates IFN regulatory factor 7 (IRF7) through RIP1. We now report that the LMP1 cytoplasmic carboxyl terminal amino acids 379 -386 bound IRF7 and activated IRF7. IRF7 activation required TRAF6 and RIP1, but not TRAF2 or TRAF3. LMP1 Y384YD386, which are required for TRADD and RIP1 binding and for NF-B activation, were not required for IRF7 binding, but were required for IRF7 activation, implicating signaling through TRADD and RIP1 in IRF7 activation. Association with active LMP1 signaling complexes was also critical for IRF7 activation because (i) a dominant-negative IRF7 bound to LMP1, blocked IRF7 association and activation, but did not inhibit LMP1 induced NF-B or TBK1 or Sendai virus-mediated IFN stimulated response element activation; and (ii) two different LMP1 transmembrane domain mutants, which fail to aggregate, each bound IRF7 and prevented LMP1 from binding and activating IRF7 in the same cell, but did not prevent NF-B activation. Thus, efficient IRF7 activation required association with LMP1 CTAR2 in proximity to LMP1 CTAR2 mediated kinase activation sites. LMP1 has a 24-aa cytoplasmic N-terminus, six hydrophobic transmembrane domains (amino acids 25 to 186) and a 200-aa cytoplasmic C-terminus (amino acids 187 to 386). The transmembrane domains induce LMP1 aggregation in plasma membrane lipid rafts and barges and constitutively activate two C-terminal cytoplasm signaling domains referred to as C-terminal activation regions (CTAR) or transformation effector sites (TES) 1 and 2, which were initially defined as amino acids 187-231 and 352-386, respectively (Fig. 1A) (2-9). CTAR1 amino acids 201 to 210 engage tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) 1, 3, 2, and 5 and CTAR2 amino acids 376-386 engage TNFRassociated death domain proteins TRADD and RIP1 (4-12). Both signaling domains activate NF-B, p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase, thereby altering cell gene expression, cell survival, and immune responses (13-17).LMP1 also induces and activates IFN regulatory factor 7 (IRF7) (18-20), a critical transcription factor for type 1 IFN (IFN)-mediated innate and adaptive immune responses (21-24). IRF7 is comprised of DNA binding, constitutive activation, virus activated, inhibitory, and signal response domains and is activated by serine 477 and 479 phosphorylation (25). Although IRF7 is expressed at low levels in nonstimulated cells, IRF7 is critical for type I IFN expression, particularly in plasmacytoid dendritic cells (24,26,27). Toll-like receptor activation, LMP1 expression, viral infection, and other signals that activate IRF3 and induce IFN ␤ (IFN␤), can up-regulate IRF7 expression (18, 21-24, 28, 29). IRF7 can bind and localize to MyD88 until ligand-activated Toll-like receptors 7, 8, or 9 engage MyD88 and activate IRF7, which enters the nucleus and up-regulates IFN stimulated response elements (ISREs) to activate I...

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“…6). However, RIP1 was critical for LMP1-induced IRF7 activation, as assayed by ISREdependent promoter responses (data not shown) and previously reported (20).…”

Section: Irf7 Amino Acids 194 -411 Bind Strongly To Ctar2 and Block Irf7mentioning

confidence: 91%

Section: Irf7 Amino Acids 194 -411 Bind Strongly To Ctar2 and Block Irf7mentioning

confidence: 99%

Section: Irf7 Amino Acids 194 -411 Bind Strongly To Ctar2 and Block Irf7mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

IRF7 activation by Epstein–Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3

Song

Izumi

Shinners

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Genomic profiling of 766 cancer‐related genes in archived esophageal normal and carcinoma tissues

Chen

Guo

Peiffer

et al. 2008

Intl Journal of Cancer

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We employed the BeadArray TM technology to perform a genetic analysis in 33 formalin-fixed, paraffin-embedded (FFPE) human esophageal carcinomas, mostly squamous-cell-carcinoma (ESCC), and their adjacent normal tissues. A total of 1,432 single nucleotide polymorphisms (SNPs) derived from 766 cancer-related genes were genotyped with partially degraded genomic DNAs isolated from these samples. This directly targeted genomic profiling identified not only previously reported somatic gene amplifications (e.g., CCND1) and deletions (e.g., CDKN2A and CDKN2B) but also novel genomic aberrations. Among these novel targets, the most frequently deleted genomic regions were chromosome 3p (including tumor suppressor genes FANCD2 and CTNNB1) and chromosome 5 (including tumor suppressor gene APC). The most frequently amplified genomic region was chromosome 3q (containing DVL3, MLF1, ABCC5, BCL6, AGTR1 and known oncogenes TNK2, TNFSF10, FGF12). The chromosome 3p deletion and 3q amplification occurred coincidently in nearly all of the affected cases, suggesting a molecular mechanism for the generation of somatic chromosomal aberrations. We also detected significant differences in germline allele frequency between the esophageal cohort of our study and normal control samples from the International HapMap Project for 10 genes (CSF1, KIAA1804, IL2, PMS2, IRF7, FLT3, NTRK2, MAP3K9, ERBB2 and PRKAR1A), suggesting that they might play roles in esophageal cancer susceptibility and/or development. Taken together, our results demonstrated the utility of the BeadArray technology for high-throughput genetic analysis in FFPE tumor tissues and provided a detailed genetic profiling of cancer-related genes in human esophageal cancer.

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Manipulation of ubiquitin/SUMO pathways in human herpesviruses infection

Jin

Qiao

Strahan

et al. 2016

Reviews in Medical Virology

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Post-translational modification of proteins with ubiquitin/small ubiquitin-like modifier (SUMO) molecules triggers multiple signaling pathways that are critical for many aspects of cellular physiology. Given that viruses hijack the biosynthetic and degradative systems of their host, it is not surprising that viruses encode proteins to manipulate the host's cellular machinery for ubiquitin/SUMO modification at multiple levels. Infection with a herpesvirus, among the most ubiquitous human DNA viruses, has been linked to many human diseases, including cancers. The interplay between human herpesviruses and the ubiquitylation/SUMOylation modification system has been extensively investigated in the past decade. In this review, we present an overview of recent advances to address how the ubiquitin/SUMO-modified system alters the latency and lytic replication of herpesvirus and how herpesviruses usurp the ubiquitin/SUMO pathways against the host's intrinsic and innate immune response to favor their pathogenesis.

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Interferon Regulatory Factor 7 Is Activated by a Viral Oncoprotein through RIP-Dependent Ubiquitination

Cited by 76 publications

References 49 publications

IRF7 activation by Epstein–Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3

IRF7 activation by Epstein–Barr virus latent membrane protein 1 requires localization at activation sites and TRAF6, but not TRAF2 or TRAF3

Genomic profiling of 766 cancer‐related genes in archived esophageal normal and carcinoma tissues

Manipulation of ubiquitin/SUMO pathways in human herpesviruses infection

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