Abstract:
:The TRAF [tumor necrosis factor receptor-associated factor] family of cytoplasmic adaptor proteins link cell-surface receptors to intracellular signaling pathways that regulate innate and adaptive immune responses. In response to activation of RIG-I (retinoic acid-inducible gene I), a component of a pattern recognition receptor that detects viruses, TRAF3 binds to the adaptor protein Cardif [caspase activation and recruitment domain (CARD) adaptor-inducing interferon-β (IFN-β)], leading to induction of type I IFNs. We report the crystal structures of the TRAF domain of TRAF5 and that of TRAF3 bound to a peptide from the TRAF-interacting motif of Cardif. By comparing these structures, we identified two residues located near the Cardif binding pocket in TRAF3 (Tyr(440) and Phe(473)) that potentially contributed to Cardif recognition. In vitro and cellular experiments showed that forms of TRAF5 with mutation of the corresponding residues to those of TRAF3 had TRAF3-like antiviral activity. Our results provide a structural basis for the critical role of TRAF3 in activating RIG-I-mediated IFN production.
journal_name
Sci Signaljournal_title
Science signalingauthors
Zhang P,Reichardt A,Liang H,Aliyari R,Cheng D,Wang Y,Xu F,Cheng G,Liu Ydoi
10.1126/scisignal.2003152subject
Has Abstractpub_date
2012-11-13 00:00:00pages
ra81issue
250eissn
1945-0877issn
1937-9145pii
5/250/ra81journal_volume
5pub_type
杂志文章abstract::The accumulation of damaged or excess proteins and organelles is a defining feature of metabolic disease in nearly every tissue. Thus, a central challenge in maintaining metabolic homeostasis is the identification, sequestration, and degradation of these cellular components, including protein aggregates, mitochondria,...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aag2298
更新日期:2017-02-28 00:00:00
abstract::Natural killer group 2D (NKG2D), an activating receptor on natural killer (NK) cells and a subset of T cells, recognizes stress-inducible proteins, including MICA and ULBP2, which are present on infected or transformed cells. Whether each NKG2D ligand (NKG2DL) has a distinct biological role is not clear. Using superre...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aal3606
更新日期:2018-04-10 00:00:00
abstract::Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Re...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.290re7
更新日期:2009-09-29 00:00:00
abstract::Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphoryl...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001993
更新日期:2011-11-08 00:00:00
abstract::Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimu...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab3156
更新日期:2015-11-24 00:00:00
abstract::Eps15 homology domain (EHD) proteins are conserved adenosine triphosphatases that are involved in membrane remodeling. EHD family members are structurally similar to the guanosine triphosphatase (GTPase) dynamin, and both are essential for the fission step of clathrin-mediated endocytosis. This Journal Club highlights...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2002989
更新日期:2012-04-24 00:00:00
abstract::The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a nutrient-sensitive protein kinase that is aberrantly activated in many human cancers. Whether dysregulation of mTORC1 signaling in normal tissues increases the risk for cancer, however, is unknown. We focused on hepatocellular carcinoma, which has been l...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002739
更新日期:2012-03-27 00:00:00
abstract::Both synaptic long-term potentiation (LTP) and long-term depression (LTD) are thought to be critical for memory formation. Dell'Acqua and co-workers now demonstrate that transient postsynaptic incorporation of Ca(2+)-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is required for...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aaf7067
更新日期:2016-04-26 00:00:00
abstract::The cytokines of the transforming growth factor-β (TGF-β) family promote the growth and differentiation of multiple tissues, but the role of only the founding member, TGF-β, in regulating the immune responses has been extensively studied. TGF-β is critical to prevent the spontaneous activation of self-reactive T cells...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar2125
更新日期:2018-08-28 00:00:00
abstract::Oxygen sensing by the carotid body is essential in vertebrates to adapt to reduced arterial oxygen tension. In this issue of Science Signaling, Yuan et al. report an intricate signaling system to transduce a physical parameter--oxygen tension--into a biological cellular signal (neural discharge) through changes in the...
journal_title:Science signaling
pub_type: 评论,杂志文章
doi:10.1126/scisignal.aab1665
更新日期:2015-04-21 00:00:00
abstract::The advent of deep-sequencing techniques has revealed that mutations in G protein-coupled receptor (GPCR) signaling pathways in cancer are more prominent than was previously appreciated. An emergent theme is that cancer-associated mutations tend to cause enhanced GPCR pathway activation to favor oncogenicity. Regulato...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aax8620
更新日期:2020-02-04 00:00:00
abstract::Chimeric antigen receptors (CARs) link an antigen recognition domain to intracellular signaling domains to redirect T cell specificity and function. T cells expressing CARs with CD28/CD3ζ or 4-1BB/CD3ζ signaling domains are effective at treating refractory B cell malignancies but exhibit differences in effector functi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat6753
更新日期:2018-08-21 00:00:00
abstract::Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2005046
更新日期:2014-03-18 00:00:00
abstract::The beta-amyloid (Abeta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble Abeta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. Abeta accumula...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.293re8
更新日期:2009-10-20 00:00:00
abstract::Degrons are the elements that are used by E3 ubiquitin ligases to target proteins for degradation. Most degrons are short linear motifs embedded within the sequences of modular proteins. As regulatory sites for protein abundance, they are important for many different cellular processes, such as progression through the...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aak9982
更新日期:2017-03-14 00:00:00
abstract::Microglia mediate neuroprotection and neuropathogenesis but have not been directly associated with behavior. As gatekeepers of the brain's immune system, microglia protect the brain from pathogens but also contribute to inflammation, which may negatively affect neurons. A recent study demonstrates a role for Hoxb8-exp...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.3147jc8
更新日期:2010-11-09 00:00:00
abstract::Chemoattractants induce cell migration through the activation of a distinct family of structurally related heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Over the past few years, several receptors in this family have been identified that recognize different classes of chemoattractants...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.259pe10
更新日期:2009-02-24 00:00:00
abstract::Cerebral amyloid angiopathy (CAA) is a vascular dysfunction disorder characterized by deposits of amyloid-β (Aβ) in the walls of cerebral vessels. CAA and Aβ deposition in the brain parenchyma contribute to dementia and Alzheimer's disease (AD). We investigated the contribution of platelets, which accumulate at vascul...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf6240
更新日期:2016-05-24 00:00:00
abstract::Chemokines were initially thought of only as regulators of the migration of developing thymocytes between different compartments of the thymus and were predicted also to be involved in early stages of thymocyte development. Recent data have suggested additional functions for the chemokine receptor CXCR4-a G protein-co...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.3119jc4
更新日期:2010-04-27 00:00:00
abstract::CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these ce...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002179
更新日期:2011-12-20 00:00:00
abstract::The vascular endothelial growth factor (VEGF) signaling pathway plays a pivotal role in normal development and also represents a major therapeutic target for tumors and intraocular neovascular disorders. The VEGF receptor tyrosine kinases promote angiogenesis by phosphorylating downstream proteins in endothelial cells...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2003572
更新日期:2013-04-16 00:00:00
abstract::Phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins play essential roles in DNA-based and RNA-based processes, such as the response to DNA damage, messenger RNA (mRNA) quality control, transcription, and translation, where they contribute to the maintenance of genome integrity and accurate gene...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000468
更新日期:2010-04-06 00:00:00
abstract::Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of s...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abd8379
更新日期:2020-12-22 00:00:00
abstract::Fgr is a member of the Src family of nonreceptor tyrosine kinases, which are overexpressed and constitutively active in many human cancers. Fgr expression is restricted to myeloid hematopoietic cells and is markedly increased in a subset of bone marrow samples from patients with acute myeloid leukemia (AML). Here, we ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat5916
更新日期:2018-10-23 00:00:00
abstract::A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2005748
更新日期:2015-01-13 00:00:00
abstract::Although multiple steroid ligands of the glucocorticoid, mineralocorticoid, and progestin families bind to and regulate the activity of mineralocorticoid receptors (MRs), the responses to these ligands differ across species. To understand how the different domains of MRs contribute to the ligand-induced activation or ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao1520
更新日期:2018-07-03 00:00:00
abstract::Although many anticancer drugs that target receptor tyrosine kinases (RTKs) provide clinical benefit, their long-term use is limited by resistance that is often attributed to increased abundance or activation of another RTK that compensates for the inhibited receptor. To uncover common and unique features in the signa...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2003994
更新日期:2013-07-16 00:00:00
abstract::The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aav2449
更新日期:2019-02-19 00:00:00
abstract::Inositol pyrophosphates are highly energetic inositol polyphosphate molecules present in organisms from slime molds and yeast to mammals. Distinct classes of enzymes generate different forms of inositol pyrophosphates. The biosynthesis of these substances principally involves phosphorylation of inositol hexakisphospha...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.2001958
更新日期:2011-08-23 00:00:00
abstract::New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aax8295
更新日期:2020-02-18 00:00:00