Abstract：
:Chronic inflammation has been strongly associated with tumor progression, but the underlying mechanisms remain elusive. Here we demonstrate that E3 ligase Itch and deubiquitinase Cyld formed a complex via interaction through 'WW-PPXY' motifs. The Itch-Cyld complex sequentially cleaved Lys63-linked ubiquitin chains and catalyzed Lys48-linked ubiquitination on the kinase Tak1 to terminate inflammatory signaling via tumor necrosis factor. Reconstitution of wild-type Cyld but not the mutant Cyld(Y485A), which cannot associate with Itch, blocked sustained Tak1 activation and proinflammatory cytokine production by Cyld(-/-) bone marrow-derived macrophages. Deficiency in Itch or Cyld led to chronic production of tumor-promoting cytokines by tumor-associated macrophages and aggressive growth of lung carcinoma. Thus, we have identified an Itch-Cyld-mediated regulatory mechanism in innate inflammatory cells.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Ahmed N,Zeng M,Sinha I,Polin L,Wei WZ,Rathinam C,Flavell R,Massoumi R,Venuprasad Kdoi
10.1038/ni.2157subject
Has Abstractpub_date
2011-11-06 00:00:00pages
1176-83issue
12eissn
1529-2908issn
1529-2916pii
ni.2157journal_volume
12pub_type
杂志文章abstract：:Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional amo...
journal_title：Nature immunology
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更新日期：2020-03-01 00:00:00
abstract：:We evaluated changes in the signaling potentials and proliferative capacity of single antigen-specific T helper (TH) cells during a primary immune response to a protein antigen. At the peak of cellular expansion in vivo all antigen-specific TH cells exhibited a profound block in CD3- and CD4-mediated mobilization of i...
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abstract：: ...
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abstract：:During the productive interaction of T cells with antigen-presenting cells (APCs), engaged receptors, including the T cell antigen receptors and their associated tyrosine kinases, assemble into spatially segregated supramolecular activation clusters (SMACs) at the area of cell contact. Here, we studied intracellular s...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni836
更新日期：2002-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2016-01-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/84298
更新日期：2001-02-01 00:00:00
abstract：:Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to i...
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doi：10.1038/87766
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.1869
更新日期：2010-06-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1463
更新日期：2007-06-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1482
更新日期：2007-08-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3514
更新日期：2016-08-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3096
更新日期：2015-03-01 00:00:00
abstract：:Plant proteins belonging to the nucleotide-binding site-leucine-rich repeat (NBS-LRR) family are used for pathogen detection. Like the mammalian Nod-LRR protein 'sensors' that detect intracellular conserved pathogen-associated molecular patterns, plant NBS-LRR proteins detect pathogen-associated proteins, most often t...
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pub_type： 杂志文章,评审
doi：10.1038/ni1410
更新日期：2006-12-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.2060
更新日期：2011-07-19 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-018-0067-5
更新日期：2018-04-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1458
更新日期：2007-05-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.3147
更新日期：2015-06-01 00:00:00
abstract：:We define here the specificity and significance of proteases in the endoplasmic reticulum (ER) that generate peptides for presentation by major histocompatibility complex (MHC) class I molecules. We show that aminopeptidases efficiently trimmed all residues except proline that flank the NH2-termini of antigenic precur...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/89800
更新日期：2001-07-01 00:00:00
abstract：: ...
journal_title：Nature immunology
pub_type： 评论,杂志文章
doi：10.1038/s41590-018-0302-0
更新日期：2019-02-01 00:00:00
abstract：:CD8+ T cells play an important role in immunity to viruses. Just how important these cells are is demonstrated by the evolution of viral strategies for blocking the generation or display of peptide-major histocompatibility complex class I complexes on the surfaces of virus-infected cells. Here, we focus on viral inter...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni1102-1019
更新日期：2002-11-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3053
更新日期：2015-02-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
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pub_type： 已发布勘误
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更新日期：2020-08-01 00:00:00
abstract：:CD46 is a widely expressed transmembrane protein that was initially identified as binding and inactivating C3b and C4b complement products. We used mice that were transgenic for one of two human CD46 isoforms that differ in their cytoplasmic domains (termed CD46-1 and CD46-2) to analyze the effect of CD46 stimulation ...
journal_title：Nature immunology
pub_type： 杂志文章
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更新日期：2002-07-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3385
更新日期：2016-04-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
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更新日期：2013-05-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1265
更新日期：2005-12-01 00:00:00
abstract：:FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (Treg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over- or under-...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3835
更新日期：2017-11-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1053
更新日期：2004-04-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章
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更新日期：2009-01-01 00:00:00
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journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni0407-325
更新日期：2007-04-01 00:00:00
