Proteasomal degradationProtein degradationProteasomeSubstratesEndoplasmic Reticulum-Associated DegradationPromotesProteins for degradationPathwayUbiquitin ligase complexFacilitatesBindsInhibitsEnzymaticLigaseSubsequentSerineMechanismCytosolicProteomeContributesIntracellularDissociationDownstreamVivoReceptorPathogensCytoplasmRegulationProcessGeneticStressActivationFunctionImportantIdentifyComplexSmallShownStudyCells
Proteasomal degradation9
- The metabolism-based inactivation of nNOS and the inhibition of heat shock protein 90 (hsp90)-based chaperones, which are known to regulate nNOS, both lead to enhanced proteasomal degradation of nNOS. (aspetjournals.org)
- In the current study, we discovered that destabilization of the dimeric nNOS, as determined by measuring the SDS-resistant dimer, is sufficient to trigger ubiquitin-proteasomal degradation. (aspetjournals.org)
- Treatment of nNOS with N G -nitro- l -arginine or 7-nitroindazole led to stabilization of the dimeric nNOS and decreased proteasomal degradation of the enzyme, consistent with that observed in cells. (aspetjournals.org)
- E3 ubiquitin ligases regulate cellular protein composition by providing target recognition and specificity to the ubiquitin-dependent proteasomal degradation pathway 12 . (nature.com)
- Our findings reveal that TLR2/NADPH oxidase-mediated Txnip proteasomal degradation facilitates pro-inflammatory cytokine production during GAS infection. (frontiersin.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)
- Cysteine-specific ubiquitination protects the peroxisomal import receptor Pex5p against proteasomal degradation. (ruhr-uni-bochum.de)
- Critical cysteine residues of Keap1 in suppression of Nrf2 basal activity and arsenic-sensing by regulating the ubiquitination-proteasomal degradation of Nrf2 protein. (cdc.gov)
- Activation of Nrf2 involves modulation of Keap1/Cul3-mediated ubiquitination-proteasomal degradation of Nrf2. (cdc.gov)
Protein degradation4
- IRE1 significantly upregulated ER-associated protein degradation (ERAD), triggering pronounced P23H rhodopsin degradation. (nih.gov)
- SIGNIFICANCE STATEMENT Ubiquitination is a well known process required for protein degradation. (jneurosci.org)
- Leo James' group in the LMB's PNAC Division has now identified surprising protein modifications that underly Trim-Away protein degradation technology, which may explain its broad applicability to deplete almost any cellular protein. (cam.ac.uk)
- Ubiquitin is a small protein that can be attached to other proteins through a process called ubiquitination, where it acts as a signal to recruit the cell's protein degradation machinery. (cam.ac.uk)
Proteasome11
- Treatment with proteasome inhibitors reversed GAS-induced Txnip degradation. (frontiersin.org)
- Ubiquitylation affects proteins in many ways: it can mark them for degradation via the proteasome, alter their cellular location, affect their activity, and promote or prevent protein interactions. (wikipedia.org)
- Only polyubiquitylation on defined lysines, mostly on K48 and K29, is related to degradation by the proteasome (referred to as the "molecular kiss of death"), while other polyubiquitylations (e.g. on K63, K11, K6 and M1) and monoubiquitylations may regulate processes such as endocytic trafficking, inflammation, translation and DNA repair. (wikipedia.org)
- Ubiquitination of AURKB by BCR(KLHL21) E3 ubiquitin ligase complex may not lead to its degradation by the proteasome. (ucsc.edu)
- It promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. (researchandmarkets.com)
- VCP primarily identifies ubiquitylated proteins in these pathways and mediates their unfolding and degradation by the 26S proteasome. (portlandpress.com)
- VCP interacts with adaptor proteins to identify ubiquitylated substrates for degradation by the proteasome. (portlandpress.com)
- Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (intechopen.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)
- 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)
Substrates1
- The function of ubiquitination relies on its mono- and polymeric isoforms attached to protein substrates. (nih.gov)
Endoplasmic Reticulum-Associated Degradation1
- The AAA-ATPase (ATPases associated with diverse cellular activities) valosin-containing protein (VCP), is essential for many cellular pathways including but not limited to endoplasmic reticulum-associated degradation (ERAD), DNA damage responses, and cell cycle regulation. (portlandpress.com)
Promotes7
- These results confirm the prediction that spinal presynaptic Fbxo3-dependent Fbxl2 ubiquitination promotes the subsequent RIM1α/Ca V 2.2 cascade in SNL-induced neuropathic pain. (jneurosci.org)
- N4BP3 promotes breast cancer metastasis via NEDD4-mediated E-cadherin ubiquitination and degradation. (bvsalud.org)
- Intriguingly, we identified a novel E3 ligase NEDD4 for E-cadherin , and further revealed that N4BP3 promotes breast cancer metastasis via NEDD4-mediated E-cadherin ubiquitination and degradation. (bvsalud.org)
- NSP1 promotes cellular mRNA degradation and prevents host mRNA translation. (cdc.gov)
- Under normal conditions, Keap1 promotes ubiquitination and eventual degradation of Nrf2. (springer.com)
- Promotes degradation of transcription factor SALL4. (tocris.com)
- promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray Syndrome. (tocris.com)
Proteins for degradation3
- CUL3 is a conserved protein of the Cullin family, comprising eight members, which contain a conserved cullin homology domain, named after its ability to select cellular proteins for degradation. (nature.com)
- Specifically, cullin-7 helps assemble a complex called an E3 ubiquitin ligase, which tags the unneeded proteins for degradation. (medlineplus.gov)
- Mutations in the CUL7 or OBSL1 gene prevent the cullin-7 protein from bringing together the components of the E3 ubiquitin ligase complex, interfering with the process of tagging unneeded proteins for degradation. (medlineplus.gov)
Pathway2
- In addition, Fbxo3 modifies this pathway by inhibiting Fbxl2-mediated RIM1α ubiquitination, suggesting that presynaptic protein ubiquitination makes a crucial contribution to the development of neuropathic pain. (jneurosci.org)
- Our results show that SLAP2 suppresses FLT3 downstream signaling pathways including AKT, ERK, p38 and STAT5 and facilitates FLT3 degradation through enhancing ubiquitination while ABL2 expression does not alter FLT3 stability or ubiquitination but partially suppresses FLT3 downstream signaling through the PI3K/AKT pathway. (lu.se)
Ubiquitin ligase complex1
- The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB. (ucsc.edu)
Facilitates1
- UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage. (nih.gov)
Binds1
- Binds cereblon and inhibits its ubiquitination. (tocris.com)
Inhibits1
- It inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. (researchandmarkets.com)
Enzymatic2
- Ubiquitylation (also known as ubiquitination or ubiquitinylation) is an enzymatic post-translational modification in which a ubiquitin protein is attached to a substrate protein. (wikipedia.org)
- Even when released, they remain largely membrane associated due to their hydrophobic nature and can be taken up by cells via a high-affinity uptake mechanism [ 23 ], which is followed by their enzymatic degradation. (degruyter.com)
Ligase4
- 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)
- Moreover, we observed that PUS10 is ubiquitinated by E3 ubiquitin ligase CRL4DCAF1 complex and the increase of PUS10 in aged HSPC is due to aging-declined CRL4DCAF1- mediated ubiquitination degradation signaling. (haematologica.org)
- The ides of MARCH5: The E3 ligase essential for peroxisome degradation by pexophagy. (ruhr-uni-bochum.de)
Subsequent2
- The mechanism of this selective proteolytic degradation, or in essence how the nNOS becomes labilized and recognized for ubiquitination and subsequent degradation, has not been determined. (aspetjournals.org)
- Subsequent phagosome maturation involves acidification of the lumen, which leads to lysosomal fusion and degradation of the internalized microbe ( 9 ). (frontiersin.org)
Serine3
- Ubiquitin is normally attached to protein lysine residues, but serine, threonine, cysteine and N-terminal ubiquitination can also occur. (cam.ac.uk)
- Enrichment of nsp1alpha-induced cytoplasmic TRAIP in turn leads to excessive K48 ubiquitination and degradation of serine/threonine-protein kinase (TBK1), thereby antagonizing TBK1-IRF3-IFN signaling. (usda.gov)
- Controlled by sequential serine-phosphorylation, ubiquitination and degradation. (lu.se)
Mechanism3
- Nevertheless, the mechanism for ubiquitination-regulated turnover of presynaptic active zone proteins in the progression of spinal plasticity-associated neuropathic pain remains unclear. (jneurosci.org)
- Autophagy is an evolutionarily conserved process of intracellular degradation, recognized as an important defense mechanism against intracellular pathogens ( 15 ). (frontiersin.org)
- The authors speculate that TRIM21 may have evolved a promiscuous ubiquitination mechanism to remain one step ahead of rapidly-evolving pathogens that can easily mutate residues normally prone to ubiquitination. (cam.ac.uk)
Cytosolic1
- The cytosolic domain of Pex22p stimulates the Pex4p-dependent ubiquitination of the PTS1-receptor. (ruhr-uni-bochum.de)
Proteome1
- The proteostasis network (PN) is an assembly of distinct dynamic molecular pathways that control the functionality of the proteome (proteome homeodynamics) during protein synthesis, folding, trafficking, and degradation. (hindawi.com)
Contributes2
- Studies investigating pain pathology have demonstrated that ubiquitination contributes to chronic pain by regulating the turnover of synaptic proteins. (jneurosci.org)
- Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. (nature.com)
Intracellular2
- Trim-Away exploits the natural function of the intracellular antibody receptor TRIM21, which targets antibody-bound pathogens for degradation when they enter the cell. (cam.ac.uk)
- Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. (nih.gov)
Dissociation1
- This in turn results in aPKCζ-mediated NUMB phosphorylation, NUMB dissociation from p53, and p53 degradation (Fig. 1a ) 12 . (nature.com)
Downstream1
- That is, RIM1α-facilitated Ca V 2.2 expression plays a role in the downstream signaling of Fbxo3-dependent Fbxl2 ubiquitination/degradation to promote spinal plasticity underlying the progression of nociceptive hypersensitivity following neuropathic injury. (jneurosci.org)
Vivo1
- We found that the inactive monomeric heme-deficient nNOS (apo-nNOS) is rapidly degraded in vitro, consistent with the finding that both metabolism-based inactivation and inhibition of hsp90-based chaperones cause the formation of apo-nNOS and enhance its degradation in vivo. (aspetjournals.org)
Receptor1
- The activation of Toll-like receptor 2 (TLR2) initiated Txnip degradation, while no further Txnip degradation was observed in TLR2-deficient bone marrow-derived macrophages. (frontiersin.org)
Pathogens1
- Targeting of bacterial pathogens by the autophagy machinery is often mediated by ubiquitination, a posttranslational modification ( 16 , 17 ). (frontiersin.org)
Cytoplasm1
- Data now suggest that delocalization, accumulation, and ubiquitination of TDP-43 in the cytoplasm of motor neurons are early dysfunctions in the cascade of the events leading to motor neuron degeneration in ALS. (medscape.com)
Regulation2
- Regulation of the tumor-suppressor BECLIN 1 by distinct ubiquitination cascades. (ruhr-uni-bochum.de)
- Regulation of peroxisomal matrix protein import by ubiquitination. (ruhr-uni-bochum.de)
Process2
- Despite the well-understood process of CUL3-mediated protein ubiquitination and degradation 12 , its target proteins in the developing central nervous system and its role in brain development remain utterly understudied. (nature.com)
- Spinal plasticity, a key process mediating neuropathic pain development, requires ubiquitination-dependent protein turnover. (jneurosci.org)
Genetic1
- Inhibition of VCP either by genetic depletion or the pharmacologic inhibitor CB-5083 increased ubiquitination and degradation of p53-R273H, leading to cell death. (aacrjournals.org)
Stress1
- En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
Activation1
- NADPH oxidase-regulated NF-κB activation and pro-inflammatory activation were induced and accompanied by Txnip degradation during GAS infection. (frontiersin.org)
Function1
- To directly test if TRIM21 N-terminal ubiquitination is required for TRIM21 function, Leo Kiss in collaboration with Jonas Weidenhausen in Irmgard Sinning's lab at the University of Heidelberg developed a method to modify the TRIM21 protein N-terminus with an acetyl group to prevent its self-ubiquitination. (cam.ac.uk)
Important2
- Studying the ubiquitination pattern of aggregated Htt fragments offers an important possibility to understand Htt degradation and aggregation processes within the cell. (nih.gov)
- 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)
Identify1
- Here we describe methods to identify post-translational modifications such as ubiquitination of aggregated mutant Htt. (nih.gov)
Complex1
- Review of the Structure of the Arabidopsis PEX4-PEX22 Peroxin Complex-Insights Into Ubiquitination at the Peroxisomal Membrane. (ruhr-uni-bochum.de)
Small1
- Autophagy stimulus-dependent role of the small GTPase Ras2 in peroxisome degradation. (ruhr-uni-bochum.de)
Shown1
- However, how TRIM21 triggers the degradation of an antibody-bound protein has not been shown until now. (cam.ac.uk)
Study1
- Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated Htt such as ubiquitination. (nih.gov)