DegradationPathwayLigasesProteolysisUbiquitinationEnzymeApoptosisRegulatesInhibitsTransferase activityProteinsPromotesLigase complexStructuralEndocytosisAutophagyAntibodyRegulationRNF168ModulateKnockoutGeneCellularMiceMechanismMammalianFacilitateChainsRecruitmentSystemCellComplexRegulatorHomeostasisDamageRoleCellsFate
Degradation27
- 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)
- Our findings reveal that TLR2/NADPH oxidase-mediated Txnip proteasomal degradation facilitates pro-inflammatory cytokine production during GAS infection. (frontiersin.org)
- The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.org)
- Pulsatile shear stress induces ubiquitin-proteasome-mediated degradation of PDCD4 via a PI3K/Akt pathway in HUVECs. (plos.org)
- Nedd4-2 is an ubiquitin ligase that catalyses the ubiquitination of proteins, resulting in proteasomal degradation. (portlandpress.com)
- Another prime degradation pathway in the cells is ubiquitin-proteasome system (UPS), in which proteins tagged by certain types of polyubiquitin chains are selectively recognized and removed by proteasome. (biomedcentral.com)
- Ubiquitin-proteasome system (UPS) and autophagy are two major cellular degradation machineries in eukaryotes, both of which are crucial in eliminating misfolded/unfolded proteins to maintain cell and tissue homeostasis and to prevent aging-related changes and a plethora of human diseases. (biomedcentral.com)
- Importantly, these structurally distinct ubiquitin modifications are recognized by effector proteins with linkage-specific ubiquitin-binding domains to result in diverse functional outcomes, such as degradation, signal transduction, and alteration in subcellular localization. (biomedcentral.com)
- We report here that a naturally occurring antibacterial peptide PR39 reversibly binds to the α7 subunit of the 26S proteasome and blocks degradation of NF-κB inhibitor IκBα by the ubiquitin-proteasome pathway without affecting overall proteasome activity. (umn.edu)
- It is now well established that Myc levels are in part regulated by ubiquitin-dependent proteasomal degradation. (silverchair.com)
- ubiquitin-mediated degradation. (nih.gov)
- Also because check donor cells had been transplanted into wild-type recipients these results support a is necessary for the standard function of HSCs progenitors and precursors as well as for terminal differentiation.10-12 a Cul4A is suggested by These results ubiquitin ligase goals a regulator of HSC function for degradation. (liveconscience.com)
- Of the 2 p27Kip1 may end up being targeted for degradation with a Cul4A-ubiquitin ligase in erythroblasts12 and in nonhematopoietic cells 18 therefore p27Kip1 overexpression Bardoxolone methyl in Cul4A -haploinsufficient stem cells might impair engraftment and self-renewal. (liveconscience.com)
- A Cul4A-ubiquitin ligase goals HoxA9 for degradation in myeloid cells however in HSCs HoxA9 promotes function.11 19 non-e of the various other Cul4A targets recognized so far offers known HSC regulatory functions. (liveconscience.com)
- Targeted protein degradation through chemical hijacking of E3 ubiquitin ligases is an emerging concept in precision medicine. (nature.com)
- Although two E3s, CRL2 VHL and CRL4 CRBN , frequently assemble with proteolysis-targeting chimeras (PROTACs) to attach lysine-48 (K48)-linked ubiquitin chains, the diversity of the ubiquitin code used for chemically induced degradation is largely unknown. (nature.com)
- These results reveal an unexpected role for K63-linked ubiquitin chains and UBE2N in degrader-induced proteasomal degradation and demonstrate the diversity of the ubiquitin code used for chemical hijacking. (nature.com)
- Fig. 6: Generality of UBE2N-mediated (neo-)substrate degradation. (nature.com)
- Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. (nature.com)
- Ciechanover, A. Intracellular protein degradation: from a vague Idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel Lecture). (nature.com)
- In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
- The ubiquitin-proteasome pathway is responsible for most eukaryotic intracellular protein degradation. (biomedcentral.com)
- The best understood function of a Ubl modification is ubiquitin-mediated proteasomal degradation. (pewtrusts.org)
- It promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. (researchandmarkets.com)
- It inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. (researchandmarkets.com)
- Huang G, Shigesada K, Ito K, Wee HJ, Yokomizo T, Ito Y. Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. (medlineplus.gov)
- Superoxide-mediated proteasomal degradation of Bcl-2 determines cell susceptibility to Cr(VI)-induced apoptosis. (cdc.gov)
Pathway9
- Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. (ed.ac.uk)
- Camptothecin (CPT) induces down-regulation of topoisomerase I (TOP1) via an ubiquitin/26S proteasome pathway. (tmu.edu.tw)
- Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. (nih.gov)
- Wnt/β-catenin signaling is a delicate and complex signal transduction pathway mediated by multiple signaling molecules, which plays a significant role in regulating human physiology and pathology. (frontiersin.org)
- This suggests the possibility that strictly regulated self-renewal mediated by Wnt signaling in cancer cells may be disturbed by the SUMOylation pathway to allow more malignant proliferation. (frontiersin.org)
- One recognized pathway for accelerated muscle protein breakdown is the ubiquitin-proteosome pathway. (massgeneral.org)
- Furthermore, .O(-)(2) induced apoptosis in response to Cr(VI) exposure by downregulating and degrading Bcl-2 protein through the ubiquitin-proteasomal pathway. (cdc.gov)
- The adenosine triphosphate (ATP)-ubiquitin-protease pathway plays a role as well. (msdmanuals.com)
- We provided evidence for Aβ-dependent dysfunction in the ubiquitin proteasome system and multivesicular body (MVB) sorting pathway (Almeida et al. (lu.se)
Ligases2
- Since bortezomib alters the manifestation of many proteins degraded from the proteasome a greater understanding of ubiquitin ligases and their substrates could Bardoxolone methyl aid the refinement of therapies to target specific subsets of proteins therefore reducing toxicity improving efficacy and ultimately improving therapies against MM and additional cancers. (liveconscience.com)
- Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
Proteolysis1
- However since Cul4A -mediated rules occurs in the protein level direct recognition of the Cul4A-ubiquitin ligase target(s) important for HSC function requires measuring protein expression levels in HSCs-technically demanding but important to understand how ubiquitin-mediated proteolysis Bardoxolone methyl regulates HSC function. (liveconscience.com)
Ubiquitination3
- RNF168-mediated ubiquitination of γH2AX at K13/15 (ub-H2AX) serves as a recruitment module for the localization of 53BP1 to DNA break sites. (nih.gov)
- Ubiquitination is a posttranslational modification involving the conjugation of the 76 amino acid ubiquitin to the lysine residue of other proteins. (biomedcentral.com)
- As a consequence, proteins can be modified by ubiquitin monomer or polymer with different length and linkage types, making ubiquitination as one of the most elaborate and versatile posttranslational modifications [ 8 , 9 , 10 ]. (biomedcentral.com)
Enzyme2
- In the first step of ubiquitin activation, the E1 enzyme binds ATP, Mg+2 and ubiquitin, and catalyses ubiquitin C-terminal acyl-adenylation (Ubiquitin-AMP). (reactome.org)
- This modification is mediated by the sequential action of E1 ubiquitin-activating enzyme, E2 ubiquitin conjugating enzyme, and E3 ubiquitin ligase [ 6 ]. (biomedcentral.com)
Apoptosis2
- We report that ROS, specifically superoxide anion (.O(-)(2), mediates Cr(VI)-induced apoptosis of human lung epithelial H460 cells. (cdc.gov)
- This study reveals a novel mechanism linking .O(-)(2) with Bcl-2 stability and provides a new dimension to ROS-mediated Bcl-2 downregulation and apoptosis induction. (cdc.gov)
Regulates3
- Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation. (broadinstitute.org)
- Baculoviral IAP repeat-containing protein 6 (BIRC6), a giant IAP with dual E2 and E3 ubiquitin ligase activity, regulates programmed cell death through unknown mechanisms. (ox.ac.uk)
- Ubiquitin carboxyl terminal hydrolase L1 negatively regulates TNFalpha-mediated vascular smooth muscle cell proliferation via suppressing ERK activation. (musc.edu)
Inhibits1
- In the present study, we show that GPC-100 has high affinity towards the chemokine receptor CXCR4, and it potently inhibits ß-arrestin recruitment, calcium flux and cell migration mediated by its ligand CXCL12. (bvsalud.org)
Transferase activity1
- Contributes to ubiquitin-protein transferase activity. (nih.gov)
Proteins6
- 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)
- The Schulman lab studies the structural basis for post-translational modification by ubiquitin and ubiquitin-like proteins (Ubls). (pewtrusts.org)
- The tetratricopeptide repeat (TPR) is a degenerate 34 amino acid sequence identified in a wide variety of proteins, present in tandem arrays of 3-16 motifs, which form scaffolds to mediate protein-protein interactions and often the assembly of multiprotein complexes. (embl.de)
- Resonance Group, Chemical of the globular proteins bovine pancreatic trypsin inhibitor (BPTI) and Center, Lund University ubiquitin in aqueous solution. (lu.se)
- Sweden range 2.6 to 49 MHz in the pD range 2 to 11 at 27°C. While the protein-induced relaxation enhancement was similar for the two proteins at high frequencies, it was an order of magnitude smaller for ubiquitin than for BPTI at low frequencies. (lu.se)
- This difference was ascribed to the abscence, in ubiquitin, of highly ordered internal water molecules, which are known to be present in BPTI and in most other globular proteins. (lu.se)
Promotes1
- The ubiquitin ligase RNF8 promotes the DNA damage response (DDR). (oncotarget.com)
Structural1
- Our study provides a structural-functional glimpse of M1-polyUb as a multiple-molecule binding platform to exert its intrinsic structural plasticity in mediating cellular signaling. (rcsb.org)
Endocytosis1
- Receptor-mediated endocytosis. (manchester.ac.uk)
Autophagy1
- We also highlight how dysregulation of ubiquitin-mediated autophagy pathways is associated with a number of human diseases and the potential of targeting these pathways for disease intervention. (biomedcentral.com)
Antibody1
- NP antibodies are not associated with protection through neutralizing activity, but VRP vaccination results in NP antibodies possessing Fc-mediated antibody effector functions, such as complement activation (ADCD) and antibody-mediated cellular phagocytosis (ADCP). (cdc.gov)
Regulation3
- In this study, we utilized a rare protective allele to uncover a TRIM62-mediated mechanism for regulation of CARD9 activation. (broadinstitute.org)
- Analysis of the levels of TOP1 cleavable complexes, SUMO-1-TOP1 conjugates, and ubiquitin-TOP1 conjugates in ZR-75-1 and BT474 cells has suggested that the heterogeneity of CPT-induced down-regulation of TOP1 in tumor cells is at least in part attributable to altered regulation of a process(es) downstream from the TOP1 cleavable complex. (tmu.edu.tw)
- The negative regulation of signaling by growth factor receptors is mediated in large part. (biomedcentral.com)
RNF1681
Modulate1
- We show that puf genetically and physically interacts with dMyc and the ubiquitin ligase archipelago ( ago ) to modulate a dMyc-dependent cell growth phenotype, and that varying Puf levels in both the eye and wing phenocopies the effects of altered dMyc abundance. (silverchair.com)
Knockout1
- CRISPR/Cas9-mediated Knockout of the Neuropsychiatric Risk Gene KCTD13 Causes Developmental Deficits in Human Cortical Neurons Derived from Induced Pluripotent Stem Cells. (nih.gov)
Gene2
- In contrast to necrosis, this form of cell death is a gene-mediated, energy-dependent event. (massgeneral.org)
- E3 ubiquitin-protein ligase Mdm2 is a protein encoded by the MDM2 gene. (researchandmarkets.com)
Cellular2
- Ubiquitin Proteasome System Current Insights into Mechanism Cellular Regu. (intechopen.com)
- The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
Mice1
Mechanism1
- To delineate the precise mechanism by which indisulam mediates the DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-indisulam-RBM39(RRM2) complex structure to a resolution of 2.3 Å. (nature.com)
Mammalian1
- Biochemical reconstitution demonstrates that the mammalian complex possesses inherent E3 ubiquitin ligase activity, using Ube2H as its cognate E2. (elifesciences.org)
Facilitate2
- Ubiquitin-mediated fluctuations in MHC class II facilitate efficient germinal center B cell responses. (ox.ac.uk)
- Mechanistically, UBE2N-catalyzed K63-linked ubiquitin chains facilitate assembly of highly complex K48/K63 and K11/K48 branched ubiquitin chains, thereby recruiting p97/VCP, UCH37 and the proteasome. (nature.com)
Chains4
- Fig. 1: Degrader-activated cIAP1 assembles branched ubiquitin chains. (nature.com)
- Fig. 3: K63 linkages serve as the base for K11/K48/K63 heterotypic ubiquitin chains. (nature.com)
- Fig. 4: Architecture of branched ubiquitin chains conjugated on cIAP1. (nature.com)
- Fig. 5: UBE2N and UBE2D cooperatively assemble branched ubiquitin chains onto cIAP1 in vitro. (nature.com)
Recruitment1
- PolyUb-mediated UBAN recruitment remains undetermined, since the recognition studies focused mostly on di-ubiquitin (diUb). (rcsb.org)
System2
- Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (intechopen.com)
- 2009). Remarkably, reduced synaptic activity in vivo in the brain (using either the whisker - barrel cortex system or treatment with benzodiazepine) reduced amyloid plaques but still damaged synapses, providing experimental evidence for a disconnect between amyloid plaques and Aβ -mediated synapse damage in AD (Tampellini et al. (lu.se)
Cell1
- During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
Complex2
- In the second step, the catalytic cystine in the E1 attacks the ubiquitin-adenylate (Ub-AMP) to form the activated ubiquitin-E1 thioester-bonded complex and an AMP leaving group. (reactome.org)
- The intermediate reaction involving the formation of the ubiquitin-AMP complex is not represented here. (reactome.org)
Regulator1
- Using a genetic screen for modifiers of Drosophila Myc ( dMyc )-induced growth, we identified and characterized a ubiquitin-specific protease (USP), Puffyeye (Puf), as a novel regulator of dMyc levels and function in vivo . (silverchair.com)
Homeostasis1
- All of these enriched genes were closely related to NaCl and KCl stress and take part in mediating the Na + and K + homeostasis in M. hupehensis . (researchsquare.com)
Damage1
- The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. (lu.se)
Role1
- We showed that the protective variant of CARD9, which is C-terminally truncated, acted in a dominant-negative manner for CARD9-mediated cytokine production, indicating an important role for the C terminus in CARD9 signaling. (broadinstitute.org)
Cells3
- En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
- We observed that the expression of RNF8 was increased in bladder cancer cells and that this change in RNF8 expression could be reversed by adenovirus-mediated shRNA treatment. (oncotarget.com)
- Cachexia is mediated by certain cytokines, especially tumor necrosis factor-alpha, IL-1b, and IL-6, which are produced by tumor cells and host cells in the tissue mass. (msdmanuals.com)
Fate1
- The ubiquitin code is a critical determinant of the fate of substrates. (nature.com)