Interaction between Interferon Consensus Sequence-binding Protein and COP9/Signalosome Subunit CSN2 (Trip15)

Cohen, Helit; Azriel, Aviva; Cohen, Tali; Meraro, David; Hashmueli, Sharon; Bech‐Otschir, Dawadschargal; Kraft, Regine; Dubiel, Wolfgang; Levi, Ben‐Zion

doi:10.1074/jbc.m004900200

Cited by 45 publications

(31 citation statements)

References 50 publications

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“…1A, compare lane 9 to lane 2). Further, we have also shown that serine 260 in IRF-8\ICSBP is essential for protein-protein interaction (21). Similar results are demonstrated here; mutation of this serine residue within the IAD of IRF-8\ICSBP eliminates its ability to negate IRF-1 (Fig.…”

Section: Both Irf-8\icsbp and Irf-4 Inhibit Irf-1-mediated Transcriptsupporting

confidence: 75%

“…Our data also show that serine 260, which is unique to the IAD of IRF-8\ICSBP, is essential for this interaction, suggesting that the phosphorylation state of this residue is essential (for more details see Ref. 21). Tyrosine phosphorylation is also essential for proper activity of IRF-8\ICSBP.…”

Section: Discussionmentioning

confidence: 57%

“…Mammalian expression vectors, which are also suitable for in vitro transcription (IVT), corresponding to IRF-1, IRF-4, PU.1, IRF-8\ICSBP, ICSBPL331P, and ICSBPS260A, were previously described (7,21).…”

Section: Plasmidsmentioning

confidence: 99%

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IFN-Stimulated Gene 15 Is Synergistically Activated Through Interactions Between the Myelocyte/Lymphocyte-Specific Transcription Factors, PU.1, IFN Regulatory Factor-8/IFN Consensus Sequence Binding Protein, and IFN Regulatory Factor-4: Characterization of a New Subtype of IFN-Stimulated Response Element

Meraro

Gleit‐Kielmanowicz

Hauser

et al. 2002

The Journal of Immunology

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Type I IFNs cause the induction of a subset of genes termed IFN-stimulated genes (ISGs), which harbor a specific DNA element, IFN-stimulated response element (ISRE). This ISRE confers the responsiveness to the IFN signal through the binding of a family of transcription factors designated IFN regulatory factors (IRFs). Some IRFs can bind to the DNA alone, such as IRF-1, which elicits transcriptional activation, or IRF-2, which leads to transcriptional repression. In addition, these factors associate with IRF-8/IFN consensus sequence binding protein (ICSBP), an immune cell-restricted IRF, and the assembled heterocomplexes lead to synergistic repression of ISRE elements. ISG15 is a prototype ISG that contains a well-characterized ISRE. Here we show that PU.1, an ETS member essential for myeloid/lymphoid cell differentiation, forms heterocomplexes with the immune-restricted IRFs, IRF-8\/ICSBP and IRF-4, which lead to transcriptional activation of ISG15. These data allowed the characterization of a subset of ISREs designated ETS/IRF response element (EIRE), which are differentially regulated in immune cells. EIREs are unique in their ability to recruit different factors to an assembled enhanceosomes. In nonimmune cells the factors will mainly include IRF members, while cell type-restricted factors, such as PU.1, IRF-8\/ICSBP, and IRF-4, will be recruited in immune cells. IRF heterocomplex formation leads to transcriptional repression, and conversely, PU.1/IRFs heterocomplex formation leads to transcriptional activation. The fact that IRF-8\/ICSBP is an IFN-γ-induced factor explains why some of the EIREs are also induced by type II IFN. Our results lay the molecular basis for the unique regulation of ISGs, harboring EIRE, in immune cells.

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Section: Both Irf-8\icsbp and Irf-4 Inhibit Irf-1-mediated Transcriptsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 57%

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IFN-Stimulated Gene 15 Is Synergistically Activated Through Interactions Between the Myelocyte/Lymphocyte-Specific Transcription Factors, PU.1, IFN Regulatory Factor-8/IFN Consensus Sequence Binding Protein, and IFN Regulatory Factor-4: Characterization of a New Subtype of IFN-Stimulated Response Element

Meraro

Gleit‐Kielmanowicz

Hauser

et al. 2002

The Journal of Immunology

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“…21,22 In mammals, CSN appears to be involved in important signal transduction pathways because of its ability to regulate protein kinases that phosphorylate c-Jun, p53, IB␣ and ICSBP/IRF-8. 21,[23][24][25] The phosphorylation of c-Jun and p53 requires direct binding to Jab1. 26 In addition, CSN cleaves the ubiquitinlike protein Nedd8 from the Cul1 subunit of the SCF 27 This "deneddylation" activity of CSN depends on the JAMM motif within the MPN domain of the Jab1/CSN5 subunit.…”

Section: Introductionmentioning

confidence: 99%

The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression

Tomoda

Kato

Tatsumi

et al. 2005

Blood

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Jab1 is a multifunctional protein associated with the signaling pathway, cellcycle regulation, and development, and acts as a key subunit of COP9 signalosome (CSN). Jab1 promotes degradation of the cyclin-dependent kinase inhibitor p27 Kip1 IntroductionThe signals triggered by oncogenic protein kinases ultimately control the cell-cycle machinery to promote cell proliferation via constitutive activation of downstream pathways. However, little is known about how oncogenic signals reach cell-cycle regulators and override the restrictions that suppress undesirable cell proliferation. Bcr-Abl is a cytoplasmic chimeric oncoprotein produced by Philadelphia chromosome translocation and found in more than 90% of patients with chronic myelogenous leukemia (CML). The constitutive tyrosine kinase activity of Bcr-Abl confers growth factor independency and transforming activity to hematopoietic cells in vitro. 1,2 Bcr-Abl activates multiple signaling cascades including the Ras/mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K)/Akt, Janus kinase (Jak)/signal transducer and activator of transcription (Stat), and Myc pathways, which are required for mitogen-activated cell proliferation, cell survival, and stress responses. Clinical studies and animal models prove that Bcr-Abl expression serves as the initiating event in the transformation by activating these pathways. [3][4][5] However, downstream elements of the signaling pathways leading to the cell-cycle machinery are poorly understood.The proliferation of mammalian cells is strictly controlled by both negative and positive regulators that specifically function during the G1 phase of the cell-cycle. 6 Among G1 regulators, the cyclin-dependent kinase inhibitor p27 Kip1 is a key component in growth control in response to extracellular signals. 7 Although mutations in the p27 gene are rare in human tumors, reduced expression of the p27 protein correlates well with both histologic aggressiveness and poor prognosis in approximately half of all human cancers. [8][9][10] These low levels of p27 result from increased 26S proteasome-mediated proteolysis. In fact, overexpression of Skp2, a Skp1-Cullin-F-box (SCF) ubiquitin ligase required for degradation of p27, inversely correlates with the reduced level of p27 in several human cancers. 11,12 Recent studies have shown that inhibition of the nuclear import of p27 by protein kinase B (PKB)/Akt-mediated phosphorylation is linked to a poor prognosis in breast cancer. [13][14][15] These results indicate that both accelerated degradation of p27 and the segregation of p27 from the nucleus to the cytoplasm are essential in tumorigenesis. In the case of CML, Bcr-Abl is reported to down-regulate the intracellular level of p27 or to inactivate p27 by cytoplasmic segregation. [16][17][18][19] It is possible that other signaling pathways involved in oncogenesis target the machinery that controls the stability and localization of p27.We previously found that Jab1 promotes p27 degradation by transporting it from the nuc...

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“…It resides primarily in the nucleus, although it may temporarily be in the cytoplasm (26). IRF-8 interacts with proteins of the Ets family, such as PU.1 and TEL, and regulates the development of myeloid cells (25,27).…”

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confidence: 99%

Toll-Like Receptor 9 Signaling Activates NF-κB through IFN Regulatory Factor-8/IFN Consensus Sequence Binding Protein in Dendritic Cells

Tsujimura

Tamura

Kong

et al. 2004

The Journal of Immunology

136

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Unmethylated CpG DNA binds to the Toll-like receptor 9 (TLR9) and activates NF-κB to induce cytokine genes in dendritic cells (DCs). IFN regulatory factor (IRF)-8/IFN consensus sequence binding protein is a transcription factor important for development and activation of DCs. We found that DCs from IRF-8−/− mice were unresponsive to CpG and failed to induce TNF-α and IL-6, targets of NF-κB. Revealing a signaling defect selective for CpG, these cytokines were robustly induced in IRF-8−/− DCs in response to LPS that signals through TLR4. IRF-8−/− DCs expressed TLR9, adaptor myeloid differentiation factor 88, and other signaling molecules, but CpG failed to activate NF-κB in −/− cells. This was due to the selective inability of −/− DCs to activate I-κB kinase αβ, the kinases required for NF-κB in response to CpG. IRF-8 reintroduction fully restored CpG activation of NF-κB and cytokine induction in −/− DCs. Together, TLR signals that activate NF-κB are diverse among different TLRs, and TLR9 signaling uniquely depends on IRF-8 in DCs.

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Interaction between Interferon Consensus Sequence-binding Protein and COP9/Signalosome Subunit CSN2 (Trip15)

Cited by 45 publications

References 50 publications

The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression

Toll-Like Receptor 9 Signaling Activates NF-κB through IFN Regulatory Factor-8/IFN Consensus Sequence Binding Protein in Dendritic Cells

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