• These results suggest TIEG and Itch contribute to a ubiquitin-dependent nonproteolytic pathway that regulates inducible Foxp3 expression and the control of allergic responses. (nih.gov)
  • The transcription factor IDEF1 regulates the response to and tolerance of iron deficiency in plants , 2007, Proc Natl Acad Sci U S A. (github.io)
  • Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson's disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. (elsevierpure.com)
  • Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson{\textquoteright}s disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. (elsevierpure.com)
  • CRISPR screen targeting E3 ligases identifies major regulators of Parkin-independent mitophagy A. Schematic depicting the CRISPR screening strategy. (medicalxpress.com)
  • Parkin deficiency delays motor decline and disease manifestation in a mouse model of synucleinopathy. (uni-muenchen.de)
  • Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recessive parkinsonism, protects against alpha-synuclein-mediated toxicity in various models.We analyzed the effects of Parkin deficiency in a mouse model of synucleinopathy to explore the possibility that Parkin and alpha-synuclein act in the same biochemical pathway. (uni-muenchen.de)
  • During late disease stages, the disease-specific neuropathological features revealed by ubiquitin- and P(S129)-alpha-synuclein-specific antibodies were similar in mice with or without Parkin. (uni-muenchen.de)
  • However, the proportion of P(S129)-alpha-synuclein-immunoreactive neuronal cell bodies and neurites co-stained for ubiquitin was lower in the absence than in the presence of Parkin, suggesting less advanced synucleinopathy. (uni-muenchen.de)
  • De plus, une recherche d'homologie de séquence a révélé la présence de ce même motif dans d'autres ubiquitines ligases, dont Parkin. (umontreal.ca)
  • Methods and Results: Transcriptional profiling of Parkin knockout mouse hearts revealed compensatory upregulation of multiple related E3 ubiquitin ligases. (wustl.edu)
  • Conclusions: Parkin deficiency and resulting mitophagic disruption produces cardiomyopathy in part by contamination of the cardiomyocyte mitochondrial pool through fusion between improperly retained dysfunctional/ senescent and normal mitochondria. (wustl.edu)
  • This study evaluated the roles of PINK1 mitochondrial kinase, and Parkin E3 ubiquitin ligase in targeting depolarized mitochondria for degradation in vivo, using quantitative measurements of mitochondria in Drosophila nervous system. (sdbonline.org)
  • The Parkinson's disease genes pink1 and parkin , which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. (sdbonline.org)
  • Parkin deficiency potentiates the RIPK1−RIPK3 interaction, RIPK3 phosphorylation and necroptosis. (elsevierpure.com)
  • Parkin deficiency enhances inflammation and inflammation-associated tumorigenesis. (elsevierpure.com)
  • Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity toward p53. (elifesciences.org)
  • p53 E3 ubiquitin protein ligase homolog (Mdm2) is an important negative regulator of p53. (molvis.org)
  • Silencing Txnip prompted TLR2-mediated inducible nitric oxide synthase (iNOS)/NO, TNF-α, and IL-6 production whereas the blockage of Txnip degradation by pharmacologically inhibiting the HECT E3 ubiquitin ligase with heclin and AMP-dependent protein kinase with dorsomorphin effectively reduced such effects. (frontiersin.org)
  • In yeast, the glucose-induced degradation-deficient (GID) E3 ligase selectively degrades superfluous gluconeogenic enzymes. (elifesciences.org)
  • Particularly in yeast, an organism where gluconeogenesis and glycolytic activity are intermittently coordinated, the multi-subunit GID E3 ligase complex specifically targets the surplus of gluconeogenic enzymes, including the conserved Fructose-1,6-bisphosphatase 1 (Fbp1), for proteasomal degradation. (elifesciences.org)
  • These results might explain how SOCS2-deficiency leads to hyper-activation of NF-κB and downstream pathological implications and posits that SOCS2 induced degradation of NDR1 may act as a switch in restricting TNFα-NF-κB pathway. (elsevierpure.com)
  • The SCFß-TRCP E3 ubiquitin ligase complex targets Lipin1 for ubiquitination and degradation to promote hepatic lipogenesis. (harvard.edu)
  • S-phase kinase-associated protein 2 (SKP2), which functions as an F-box protein as part of the SKP1-Cullin 1-F-box (SCF) E3 ubiquitin ligase complex, promotes the degradation of cell-cycle inhibitory proteins such as p27 and stimulates ubiquitination and activation of AKT signaling. (aacrjournals.org)
  • Overexpression of HSPA12A in RCC cells unstabilizes CD147 through increasing its ubiquitin-proteasome degradation, thereby inhibits lactate export and glycolysis, and ultimately suppresses RCC cell migration. (thno.org)
  • Hannah Elcocks et al, FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX levels, The EMBO Journal (2023). (medicalxpress.com)
  • This gene provides instructions for making a protein that plays a role in the ubiquitin-proteasome system, which is the cell machinery that breaks down (degrades) unwanted proteins. (medlineplus.gov)
  • A hallmark of proteome balance is the ubiquitin-proteasome system (UPS) that degrades roughly 80% of multi-ubiquitinated proteins ( Collins and Goldberg, 2017 ). (elifesciences.org)
  • Overall, this study reveals the impact of cln5 -deficiency on gene expression in D. discoideum , provides insight on the genes and proteins that play a role in regulating Cln5-dependent processes, and sheds light on the molecular mechanisms underlying CLN5 disease. (frontiersin.org)
  • It was previously not feasible to test the functional redundancy of CBL proteins in specific populations of T cells using existing models because their generalized CBL-B deficiency leads to altered and/or enhanced function of all T cell subsets and other immune cells, including B cells, macrophages, mast cells, neutrophils, and NKT cells. (unmc.edu)
  • ITCH is a HECT domain E3 ubiquitin ligase that is ablated in non-agouti-lethal 18H (aka Itchy) mice. (wikipedia.org)
  • In humans ITCH deficiency causes altered physical growth, craniofacial morphology defects, defective muscle development, and aberrant immune system function. (wikipedia.org)
  • The E3 ubiquitin ligase Itch associated with and promoted conjugation of ubiquitin to the transcription factor TIEG1. (nih.gov)
  • Itch cooperated with TIEG1 to induce Foxp3 expression, which was reversed by TIEG1 deficiency. (nih.gov)
  • Transcriptional analysis of endophilin-A mutant mice, complemented by proteomics, highlighted ataxia- and protein-homeostasis-related genes and revealed upregulation of the E3-ubiquitin ligase FBXO32/atrogin-1 and its transcription factor FOXO3A. (psu.edu)
  • The rice transcription factor IDEF1 is essential for the early response to iron deficiency, and induces vegetative expression of late embryogenesis abundant genes , 2009, Plant J. (github.io)
  • Finally, around 5% of patients have loss of function mutations in the UBE3A gene, a gene encoding E6-AP, a ubiquitin protein ligase. (bmj.com)
  • Study uncovers role of specific ion channel in brain network hyperactivity leading to epileptic seizures, linked to Ubiquitin Protein Ligase E3A (UBE3A) gene deficiency in neurons. (healthxchange.sg)
  • AS and autism share a common genetic basis, specifically, a disruption in the number of copies of the Ubiquitin Protein Ligase E3A (UBE3A) gene. (healthxchange.sg)
  • All result in a deficiency of the E6-AP protein, which is involved in the process of ubiquitination. (bmj.com)
  • During this 2-step process, the ER transmembrane E3 ligase TRIM13 undergoes auto-ubiquitination via lysine 63 (K63) linkage chains and acts as a ligand for the autophagic receptor SQSTM1/p62 (sequestosome 1). (nih.gov)
  • In this study, we used comparative transcriptomics to identify differentially expressed genes underlying cln5 -deficiency phenotypes during growth and the early stages of multicellular development. (frontiersin.org)
  • In this study, we showed that the N-degron pathway mediates ubiquitin (Ub)-dependent reticulophagy. (nih.gov)
  • This compound disrupted the interaction of SKP2 with SKP1 in the SCF complex via binding to the SKP2 F-box domain, in particular residues Trp97 and Asp98, resulting in inhibition of SKP2 E3 ligase activity. (aacrjournals.org)
  • The Casitas B-lineage Lymphoma (CBL)-family of ubiquitin ligases (E3s) are essential negative regulators of T cell activation that impinge on thymic selection as well as anergy induction programs. (unmc.edu)
  • Consistent with abnormal activation of Notch signaling and impaired repair of DSBs in Rnf8-mutant mammary epithelial cells, we observed increased risk of mammary tumorigenesis in mouse models for RNF8 deficiency. (jci.org)
  • Notably, deficiency of RNF8 sensitized breast cancer cells to combination of pharmacological inhibitors of Notch signaling and poly(ADP-ribose) polymerase (PARP), suggesting implications for treatment of breast cancer associated with impaired RNF8 expression or function. (jci.org)
  • RPE1-Cas9i-mt-mKeima cells were transduced with a lentiviral CRISPR sgRNA library targeting 606 E3 ligases. (medicalxpress.com)
  • LAPMT5 is a lysosomal membrane protein preferentially expressed in immune cells ( 5 , 6 ) and hematopoietic cells ( 7 ), having a close interaction with the Nedd4 ( 8 ), a member of the E3 ubiquitin ligases family ( 8 ). (spandidos-publications.com)
  • An interaction of HSPA12A with HRD1 ubiquitin E3 ligase was detected in RCC cells. (thno.org)
  • Nous croyons que l'importance de ce motif ne se restreint pas à MARCH1, mais serait généralisée à d'autres E3 ligases. (umontreal.ca)
  • Tao Q, Tianyu W, Jiangqiao Z, Zhongbao C, Xiaoxiong M, Long Z, Jilin Z. Tripartite Motif 8 Deficiency Relieves Hepatic Ischaemia/reperfusion Injury via TAK1-dependent Signalling Pathways. (ijbs.com)
  • Tripartite motif (Trim) 8 is an E3 ubiquitin ligase, interacting with and ubiquitinating diverse substrates, and is closely involved in innate immunity. (ijbs.com)
  • SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. (elifesciences.org)
  • Conversely, depletion of NDR1 rescues the effect of SOCS2-deficiency on TNFα-induced NF-κB transactivation. (elsevierpure.com)
  • Mechanistically, our study suggests that Trim8 deficiency may elicit hepatic protective effects by inhibiting the activation of transforming growth factor β-activated kinase 1 (TAK1)-p38/JNK signalling pathways. (ijbs.com)
  • In conclusion, our study demonstrates that Trim8 deficiency plays a protective role in hepatic I/R injury by inhibiting the activation of TAK1-dependent signalling pathways. (ijbs.com)
  • Consistently with the observation of Crohn's disease (CD) in XIAP deficiency, the RING activity of XIAP was recently shown to be required for NOD2-dependent immune responses. (bmj.com)
  • Biochemical reconstitution demonstrates that the mammalian complex possesses inherent E3 ubiquitin ligase activity, using Ube2H as its cognate E2. (elifesciences.org)
  • This open form of DNA is a substrate for the intrinsic exonuclease activity of most ligases, resulting in cloning artefacts and dramatically reducing final library quality. (biochem2.com)
  • Considering the possible occurrence of life threatening complications in XIAP deficiency (eg, HLH) and a possible curative (albeit hazardous) treatment option by HSCT, we highly recommend screening for XIAP deficiency in any male patient with severe CD, including those with onset beyond early childhood. (bmj.com)
  • As in Lewy bodies, ubiquitin-immunoreactivity, albeit less abundant, was invariably co-localized with P(S129)-alpha-synuclein. (uni-muenchen.de)
  • In the cell, RNF213 was shown to be involved in fatty acid metabolism ( 11 ), and to associate with intracellular lipid droplets in a manner dependent on its E3 ligase and ATPase activities ( 12 ). (biorxiv.org)
  • Endothelial lipid phosphate phosphatase-3 deficiency that disrupts the endothelial barrier function is a modifier of cardiovascular development. (harvard.edu)
  • A selective inhibitor of SKP2 E3 ligase impairs cancer stem cell self-renewal and tumor growth. (aacrjournals.org)
  • Using a SOCS2 mice model of colitis we show that SOCS2-deficiency is pro-inflammatory and negatively correlates with NDR1 and nuclear p65 levels. (elsevierpure.com)
  • The E3 ubiquitin ligase RNF8 plays critical roles in maintaining genomic stability by promoting the repair of DNA double-strand breaks (DSBs) through ubiquitin signaling. (jci.org)
  • Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots. (github.io)
  • Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament light chain and neurodegeneration. (mpg.de)
  • We report here that endophilin-A deficiency results in impaired movement, age-dependent ataxia, and neurodegeneration in mice. (psu.edu)
  • Transportation of LAPTM5 from Golgi to lysosome could be inhibited by deficiency of Nedd4, a key member of E3 ubiquitin ligase family overexpressing in invasive BCa and promoting its progression. (spandidos-publications.com)
  • Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. (aacrjournals.org)
  • Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. (nature.com)
  • RNF213/ALO17/mysterin (Ring Finger Protein 213) is the largest known human single-chain E3 ubiquitin ligase, first described as the major susceptibility factor for Moyamoya disease (MMD) ( 1 ), a disorder which causes aberrant vasculature development commonly leading to stroke and other complications ( 2 ). (biorxiv.org)
  • The cryo-EM structure of the trapped RNF213:E2∼Ub intermediate reveals RNF213 C-terminal domain as the E2 docking site, which positions the ubiquitin-loaded E2 proximal to the catalytic zinc finger, facilitating nucleophilic attack of Cys4462 on the E2∼Ub thioester. (biorxiv.org)
  • RNF213 is a giant E3 ubiquitin ligase and a major susceptibility factor of Moyamoya disease, a cerebrovascular disorder that can result in stroke or death. (biorxiv.org)
  • This antitumorigenic effect was mediated by induction of apoptosis and p53-independent cellular senescence and suppression of AKT-driven glycolysis in cancer cell lines, similar to the effects of Skp2 deficiency. (aacrjournals.org)
  • Two of them are alive and cured from IBD, generally documenting efficacy of this treatment for XIAP deficiency associated CD. (bmj.com)
  • 1 XIAP deficiency, caused by X-linked inherited mutations in BIRC4 , is highlighted as a mendelian cause of very early onset IBD. (bmj.com)
  • deficiency accelerates the transition to heart failure in pressure overload hypertrophy. (omicsdi.org)
  • To the best of our knowledge, this is the first report of an identified E3 ligase for NDR1. (elsevierpure.com)