Catalyzes ubiquitin protein ligases. Medical search. Frequent questions

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)
Plasticity of the cullin-RING ligase repertoire shapes sensitivity to ligand-induced protein degradation. (nature.com)
Jan, M., Sperling, A. S. & Ebert, B. L. Cancer therapies based on targeted protein degradation-lessons learned with lenalidomide. (nature.com)
Cell-fate-determinant molecule NUMB-interacting protein (TBC1D15) is overexpressed and contributes to p53 degradation in TICs. (nature.com)
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)
However, how TRIM21 triggers the degradation of an antibody-bound protein has not been shown until now. (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)
Furthermore, proteins targeted by Trim-Away inside living cells were found to be ubiquitinated prior to their degradation. (cam.ac.uk)
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)
In the UPS, ubiquitin-conjugating enzymes and ubiquitin ligases append poly-ubiquitin chains onto misfolded protein substrates signaling for their degradation. (unlv.edu)
We discuss how these results may have broad implications for the regulation of PQC-mediated protein degradation. (unlv.edu)
The overall goal of this proposal is to develop a biological reagent that leads to degradation of any intracellular protein bound by IgG. (alphathera.com)
The overall goal of this proposal is to develop a biological reagent that not only enables the facile cytosolic delivery of any 'off-the-shelf', native immunoglobulin G (IgG) antibody, but also leads to degradation of any intracellular protein bound by the IgG. (alphathera.com)
By harnessing TRIM21, protein degradation is epitope agnostic and only a sub-stoichiometric amount of cytosolically delivered antibody can catalyze multiple rounds of target protein degradation. (alphathera.com)
Since pAbBDs derived from protein G bind to the same IgG site as TRIM21, i.e. the FcRn binding site, the TRIM21-mediated degradation pathway is not triggered when using pAbBD-ApP fusions to facilitate cytosolic IgG delivery. (alphathera.com)
LC3-II also binds to the adaptor protein p62/sequestosome-1 (SQSTM1), which is involved in trafficking proteins into the proteasome and serves to facilitate the autophagic degradation of ubiquitinated protein aggregates. (baxkyardgardener.com)
PROTACs hijack the cell's natural ubiquitin-proteasome system (UPS) to recruit various E3 ligases and induce protein degradation. (musechem.com)
USP7 as a deubiquitinase sustained PLK1 protein stability via the C223 site, and inversely, USP7 inhibition by P5091 promoted the protein degradation of PLK1 through the ubiquitination-proteasome pathway. (biomedcentral.com)
USP7 inhibition induces cell apoptosis and cell cycle G2/M arrest, and overcomes taxane resistance by inducing the protein degradation of PLK1, resulting in chromosome misalignment in mitosis. (biomedcentral.com)
In addition to the autophagy-lysosome system, the ubiquitin-proteasome system (UPS) takes up approximately 80 to 90% of intracellular protein degradation [ 1 ]. (biomedcentral.com)
In UPS-induced protein degradation, ubiquitin binds to target proteins and catalyzes them by a hierarchical cascade comprising E1, E2 and E3 ubiquitin ligases [ 2 ]. (biomedcentral.com)
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. (dict.cc)
Proteins marked for degradation are covalently linked to ubiquitin. (dict.cc)
Herein, we demonstrate that butyrate and other short chain fatty acids supplemented to model human intestinal epithelia in vitro and human tissue ex vivo results in loss of neddylated Cul-1 and show that physiological concentrations of butyrate modulate the ubiquitination and degradation of a target of the E3-SCFβ-TrCP ubiquitin ligase, the NF-κB inhibitor IκB-α. (emory.edu)
The cascade of JWH 073 activation (E1) conjugation (E2) and ubiquitin-ligase (E3)-type enzymes catalyzes the conjugation of the ubiquitin chain to the proteins designated for degradation. (buyresearchchemicalss.net)
Ubiquitin (purple) is a molecular signal important for mediating multiple steps in membrane protein trafficking, function, and degradation. (elifesciences.org)
Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. (icr.ac.uk)
Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. (icr.ac.uk)
Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. (icr.ac.uk)
Interacts with human herpes virus 1 protein ICP0 and associates with the proteasome for degradation (PubMed:11447293, PubMed:11805320, PubMed:12060736). (icr.ac.uk)
Subsequently, TAK1 activates the IKK complex and mediates IκBα phosphorylation and ubiquitin (Ub)-dependent proteasomal degradation, leading to the rapid and transient nuclear translocation of the classical NF-κB dimers. (xiahepublishing.com)
The concept of targeted protein degradation challenges conventional rules for pharmaceutical drug discovery. (cisbio.net)
Rather than directly modify protein function by occupying an active site, PROteolysis TArgeting Chimeras (PROTACs) exploit the cell's own degradation machinery to irreversibly destroy target proteins. (cisbio.net)
PROteolysis TArgeting Chimeras (PROTACs) are small two-headed (heterobifunctional) molecules that hijack the cell's protein degradation machinery to irreversibly destroy the target. (cisbio.net)
The resulting polyubiquitin chain flags the target protein for degradation by the proteasome. (cisbio.net)
The resulting ternary complex catalyzes polyubiquitination of the target protein, tagging it for degradation by the proteasome. (cisbio.net)

Ubiquitin ligases catalyse the transfer of ubiquitin from the ubiquitin conjugating enzyme (E2), to the substrate protein. (embl-heidelberg.de)
This enzyme catalyzes a transferase reaction. (planteome.org)
A protease is an enzyme that conducts proteolysis, i.e., the protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain which form the protein. (stratech.co.uk)
TRIM21 is a ubiquitin ligase enzyme, meaning that it can catalyse the attachment of ubiquitin molecules to proteins. (cam.ac.uk)
These proteins catalyze the transfer of the ubiquitin protein from a ubiquitin E2 enzyme to a protein substrate. (utsouthwestern.edu)
The covalent attachment of ubiquitin to a target protein is catalyzed by the sequential action of a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). (bmbreports.org)
Ibarra, Rebeca Lea, "The San1 Ubiquitin Ligase Functions Preferentially with Ubiquitin-Conjugating Enzyme Ubc1 During Protein Quality Control" (2016). (unlv.edu)
Mechanistic and structural evaluation of a Drosophila melanogaster enzyme, arylalkylamine N -acetyltransferase like 7, that catalyzes the formation of N -acetylarylalkylamides and N -acetylhistamine. (bu.edu)
The E1-like enzyme Atg7 activates Atg12 and LC3-I, and the E2-like enzymes Atg10 (for activation of Atg12) and Atg3 (for LC3-I). Atg5 is conjugated to the Atg12 protein and this complex acts as an E3 ubiquitin ligase to catalyse the conjugation of LC3-I to PE in the process of sequestration. (baxkyardgardener.com)
Ubiquitin thioesterase OTUB1 also known as otubain-1 is an enzyme that in humans is encoded by the "OTUB1" gene. (dict.cc)
This enzyme contains an E2 binding domain, which resembles ubiquitin , and recruits the catalytic core of the E2 enzyme UBE2M (Ubc12) in a similar manner to that in which ubiquitin interacts with ubiquitin binding domains. (dict.cc)
CDC34" is a gene that in humans encodes the protein Ubiquitin -conjugating enzyme E2 R1. (dict.cc)
Ubiquitin specific peptidase 9, Y-linked (fat facets-like, Drosophila), also known as USP9Y, is an enzyme which in humans is encoded by the "USP9Y" gene. (dict.cc)
A ubiquitin -activating enzyme, or E1, first activates the ubiquitin by covalently attaching the molecule to its active site cysteine residue. (dict.cc)
Such studies exposed that mutated α-synuclein is definitely a major constituent of Lewy body in PD patient brains and that mutant forms of the ubiquitin E3 ligase parkin or the ubiquitin carboxy-terminal hydrolase UCH-L1 (a deubiquinating enzyme) may result in UPS dysfunction and also result in hereditary forms of PD. (buyresearchchemicalss.net)
Parkin recruits substrate proteins as well as an E2 enzyme (e.g. (buyresearchchemicalss.net)

The APC, in conjunction with other enzymes, assembles multi-ubiquitin chains on a variety of regulatory proteins, thereby targeting them for proteolysis by the 26S proteasome. (embl-heidelberg.de)
They belong to the class of enzymes known as hydrolases, which catalyse the reaction of hydrolysis of various bonds with the participation of a water molecule. (stratech.co.uk)
These enzymes are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated cascades (e.g., the blood-clotting cascade, the complement system, apoptosis pathways, and the invertebrate prophenoloxidase-activating cascade). (stratech.co.uk)
Proteases determine the lifetime of other proteins playing an important physiological role like hormones, antibodies, or other enzymes-this is one of the fastest "switching on" and "switching off" regulatory mechanisms in the physiology of an organism. (stratech.co.uk)
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)
Our results demonstrate that San1 can function with 2 ubiquitin-conjugating enzymes, Cdc34 and Ubc1. (unlv.edu)
Recently, the Tsourkas lab, at the University of Pennsylvania, developed photo-reactive antibody-binding domains (pAbBDs) derived from protein G that can be used for the rapid and site-specific covalent labeling of the IgG Fc domain with small molecules, polypeptides, proteins, or enzymes. (alphathera.com)
Inversely, the ubiquitination is removed from the labeled proteins or from polyubiquitin chains by deubiquitinating enzymes (or deubiquitinases, DUBs). (biomedcentral.com)
Ubiquitin -AMC is prepared by the C-terminal derivatization of ubiquitin with 7-amino-4-methylcoumarin and has been shown to be a useful and sensitive fluorogenic substrate for wide range of deubiquitinylating enzymes (DUBs), including ubiquitin C-terminal hydrolases (UCHs) and ubiquitin specific proteases (USPs). (dict.cc)
Microbial pathogens exploit this post-translational modification process by encoding molecular mimics of E3 ubiquitin ligases, eukaryotic enzymes that catalyze the final step in the ubiquitylation cascade. (icr.ac.uk)
The E3 ligase activity of RavN was located within its N-terminal region and was dependent upon interaction with a defined subset of E2 ubiquitin-conjugating enzymes. (icr.ac.uk)
E2 ubiquitin-conjugating enzymes catalyze the attachment of ubiquitin to lysine residues of target proteins. (rcsb.org)
These include proteins associated with the sarcolemma (see image below), proteins associated with the contractile apparatus (see image below), and various enzymes involved in muscle function. (medscape.com)

The covalent attachment of ubiquitin (Ub) to target proteins represents one of the most versatile and common post-translational modifications in eukaryotic cells. (baypat.de)
The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. (icr.ac.uk)
The activity of this ubiquitin ligase is regulated via covalent modification of the Cullin-1 subunit by the ubiquitin-like protein NEDD8. (emory.edu)
Ubiquitylation describes the covalent attachment of a small 76-amino acid protein, ubiquitin, to other proteins. (ddw-online.com)
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. (icr.ac.uk)

Maturation (elongation, curvature, and closure) is regulated via ubiquitin-like conjugation systems, which regulate LC3 (also known as Atg8/microtubule-associated protein 1 light chain 3 [LC3]-I/II). (baxkyardgardener.com)
B ) Enzymatic cascade of ubiquitination, including the ATP-dependent activation of ubiquitin ( E1 ), ubiquitin conjugation ( E2 ), and ultimate ubiquitin transfer to target substrate ( E3 ). (elifesciences.org)

The BRCA1 RING motif is flanked by alpha helices formed by residues 8-22 and 81-96 of the BRCA1 protein. (wikipedia.org)
Proteases are involved in digesting long protein chains into short fragments, splitting the peptide bonds that link amino acid residues. (stratech.co.uk)
Ubiquitin is normally attached to protein lysine residues, but serine, threonine, cysteine and N-terminal ubiquitination can also occur. (cam.ac.uk)
The finding that Trim-Away degrades proteins by directly ubiquitinating them led the researchers to ask which residues ubiquitin is attached to. (cam.ac.uk)
Surprisingly, they found that if they removed all lysine residues from a protein and blocked its N-terminus by acetylation the protein was still efficiently degraded by Trim-Away. (cam.ac.uk)
An important signaling "code" in the multiple-step NF-κB activating cascade consists of different ubiquitin (Ub) chains that are assembled on the different effector proteins through different lysine residues in the Ub molecule. (iucc.ac.il)

E3 ubiquitin-protein ligase that catalyzes 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains formation. (nih.gov)
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)
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)
Together with this unique set of proteins in the cascade, Ub chains form the platform for the binding of downstream interacting partners. (iucc.ac.il)
Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. (icr.ac.uk)

Robust cullin-RING ligase function is established by a multiplicity of poly-ubiquitylation pathways. (nature.com)
This review focuses on an up-to-date understanding of the functions of E3 ligases in cancers and debates the perspectives of cancer cells that rely on inhibition or activation of ubiquitylation of target proteins. (bmbreports.org)
The kinetics of protein ubiquitylation are paramount since a balance must be achieved between the rapid removal of misfolded proteins versus providing sufficient time for protein chaperones to attempt refolding. (unlv.edu)
To uncover the molecular basis for how PQC substrate ubiquitylation rates are controlled, the reaction catalyzed by nuclear ubiquitin ligase San1 was reconstituted in vitro. (unlv.edu)
Notably, a homogeneous peptide that mimics a misfolded PQC substrate was developed and enabled quantification of the kinetics of San1-catalyzed ubiquitylation reactions. (unlv.edu)
As a major obstacle for a detailed in-vitro analysis of ubiquitylation, chemical generation of Ub- and Ubl-conjugates has proven to be difficult and are often limited to easy and refoldable target proteins. (baypat.de)
We present a new method allowing for the site-specific ubiquitylation and SUMOylation of target proteins - both in vitro and in cellulo* . (baypat.de)
Here, we show that the Legionella pneumophila effector protein RavN belongs to a growing class of bacterial proteins that mimic host cell E3 ligases to exploit the ubiquitylation pathway. (icr.ac.uk)
L ike protein phosphorylation by kinases, protein ubiquitylation regulates many aspects of cell function and provides a wealth of drug target opportunities across many therapeutic areas including cancer, cardiovascular, metabolism, inflammation, neurodegeneration and infectious diseases. (ddw-online.com)

The E3 ubiquitination step determines the overall specificity for ubiquitination of the target protein, and the activated ubiquitin is usually transferred to a lysine residue in the substrate. (bmbreports.org)
The RNF168 E3 ubiquitin ligase catalyzes the mono-ubiquitination of histone H2A at lysine (K)13/15 (mUb-H2A), forming a binding module for DNA repair proteins. (nih.gov)
As previously said USP27X belongs to deubiquitinase family, thus its main function is catalyzing the removal of ubiquitin from substrates (cleaving the bond between the last aminoacid of ubiquitin, glycine 76, and a lysine residue on the substrate), the reversal process of ubiquitination, regulating the fate of ubiquitin-conjugated proteins. (dict.cc)

The protein encoded by this gene is a type I transmembrane protein that localizes to the endocytic pathway. (nih.gov)
SUMOylation is a post-translational modification of proteins that has been found to play a major role in the Wnt/β-catenin signaling pathway. (frontiersin.org)
Proteins associated with the Wnt/β-catenin pathway have been identified as SUMOylated substrates, and evidences suggested that the initiation and progression of cancers depended on the function of the SUMOylation ( 23 ). (frontiersin.org)
Ubiquitin -related modifier-1 (URM1) is a ubiquitin-like protein that modifies proteins in the yeast ubiquitin-like urmylation pathway. (dict.cc)
Populations of enteric bacteria can inhibit the NF-κB pathway by blockade of IκB-α ubiquitination, a process catalyzed by the E3-SCFβ-TrCP ubiquitin ligase. (emory.edu)
A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to process p100 to p52, thereby forming the RelB/p52 heterodimer to initiate the expression of target genes. (xiahepublishing.com)

This enables the E3 ligase complex to catalyze ubiquitination of the target. (cisbio.net)

The p53 interacting partner protein NUMB (homology of numb protein) preserves this intrinsic cellular asymmetry by preventing ubiquitin-mediated proteolysis of p53 catalyzed by the MDM2 E3 ubiquitin ligase 11 . (nature.com)
Surprisingly, however, in infection and Trim-Away experiments carried out together with Tyler Rhinesmith, he found that the N-terminally acetylated TRIM21 was still able to efficiently degrade antibody-bound cellular proteins and invading pathogens. (cam.ac.uk)
This mode of action may also explain why Trim-Away technology can be used to degrade a wide-range of cellular proteins. (cam.ac.uk)
We recently described the structure of M. musculus RNF213 (PDB: 6TAX) and characterized its enzymatic activity, revealing it as a large monomeric protein with a functional dynein-like AAA (ATPases Associated with diverse cellular Activities) core that exists alongside a novel E3 ligase module ( 16 ). (biorxiv.org)
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)
We use chemical, semi-synthetic, biophysical, and cellular approaches to elucidate mechanisms for how post-translational modifications regulate protein function. (bu.edu)
This allows for a detailed analysis of ubiquitin marks in cellular processes as well as potential involvement in different human diseases. (baypat.de)
SUMOylation of proteins is an important mechanism in cellular responses to environmental stress ( 21 , 22 ). (frontiersin.org)
Protein stability is critical for normal cellular homeostasis. (biomedcentral.com)
DUBs are critical in cellular growth, survival and homeostasis, and are responsible for the turnover, localization and activity of their substrate proteins. (biomedcentral.com)
Limb-girdle muscular dystrophy (LGMD) protein defects occur in several pathways involved in the biologic function of muscle and can be divided into groups based on cellular localization. (medscape.com)

The choice of linker strategy depends on the specific requirements of the target protein and E3 ligase interaction, as well as the desired pharmacokinetic properties of the PROTAC molecule. (musechem.com)
However, by design, the vast majority of pharmaceutical drugs are like single-use bullets, each drug molecule capable of taking out just one target protein. (cisbio.net)
Each PROTAC molecule can seek out and destroy many protein molecules in its lifetime. (cisbio.net)
Each heterobifunctional PROTAC molecule targets a protein of interest (POI), serving as a bridge to bring it in close proximity with an E3 ligase. (cisbio.net)
Over the past decade there has been an explosion in the number of small molecule inhibitors targeting protein kinases that regulate key cancer-related pathways and signal transduction cascades. (cisbio.net)

Moreover, we identify a distinct, N-terminal, higher affinity interaction interface between LRRK2 phosphorylated Rab8 and Rab10 termed 'Site #2', that can retain LRRK2 on membranes in cells to catalyze multiple, subsequent phosphorylation events. (stanford.edu)
Post-translational modifications (PTMs) of proteins, including phosphorylation, acetylation, ubiquitination, and SUMOylation, can regulate the function of proteins, determine the active state and subcellular location of proteins, and dynamically interact with other proteins related to carcinogenesis and progression ( 17 - 20 ). (frontiersin.org)

Abstract ARAP2 is an Arf GAP that has previously been reported to affect focal adhesions (FAs) by regulating Arf6 and integrin trafficking and to bind to the adaptor proteins APPL1. (bio2009.org)

The anaphase promoting complex or cyclosome (APC2) is an E3 ubiquitin ligase which is part of the SCF family of ubiquitin ligases. (embl-heidelberg.de)
The anaphase-promoting complex (APC) or cyclosome is a multi-subunit E3 protein ubiquitin ligase that regulates important events in mitosis, such as the initiation of anaphase and exit from telophase. (embl-heidelberg.de)
The anaphase-promoting complex or cyclosome (APC) is an unusuallycomplicated ubiquitin ligase, composed of 13 core subunits and either oftwo loosely associated regulatory subunits, Cdc20 and Cdh1. (embl-heidelberg.de)

BRCA1 combines with other tumor suppressors, DNA damage sensors and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). (wikipedia.org)
The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. (wikipedia.org)
DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)

Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (intechopen.com)
In eukaryotic cells, the removal of misfolded proteins is primarily accomplished by the ubiquitin-proteasome system (UPS). (unlv.edu)

The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. (wikipedia.org)

Reconstituting Trim-Away in vitro revealed that, in addition to ubiquitinating itself, TRIM21 can also directly ubiquitinate antibody-bound proteins. (cam.ac.uk)
In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:22496338). (icr.ac.uk)

PROTACs, or Proteolysis Targeting Chimeras, consist of three components: a ligand for the target protein (POI), a ligand for the E3 ubiquitin ligase, and a linker that connects the two parts. (musechem.com)

Each PROTAC consists of a linker with a ligand on one end to confer target specificity, and a different ligand on the other end to engage the cell's ubiquitin system. (cisbio.net)

Once inside cells the antibody binds its protein target, forming a protein-antibody complex that is recognised by TRIM21 and destroyed within minutes. (cam.ac.uk)
N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. (elifesciences.org)
VHL is part of the E3 ubiquitin ligase complex CUL2-RBX1-ElonginB-ElonginC-VHL, consisting of two structural domains with specific binding sites. (musechem.com)
USP7 protein was detected in the PLK1-interacted protein complex. (biomedcentral.com)
Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. (icr.ac.uk)
Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and RBX1. (icr.ac.uk)
This process is characteristically slow and persistent, and is regulated in a strict and complex manner through the activity of a variety of proteins. (xiahepublishing.com)
Intrinsically disordered regions in Pex13 and Pex5 resemble those found in nuclear pore complex proteins. (tcdb.org)

Proteases can either break specific peptide bonds, depending on the amino acid sequence of a protein, or break down a complete peptide to amino acids. (stratech.co.uk)
Acid proteases secreted into the stomach (such as pepsin) and serine proteases present in duodenum (trypsin and chymotrypsin) enable us to digest the protein in food. (stratech.co.uk)
Bacteria also secrete proteases to hydrolyze (digest) the peptide bonds in proteins and therefore break the proteins down into their constituent monomers (amino acids). (stratech.co.uk)
Bacterial and fungal proteases are particularly important to the global carbon and nitrogen cycles in the recycling of proteins, and such activity tends to be regulated by nutritional signals in these organisms. (stratech.co.uk)
Amplite™ Universal Fluorimetric Protease Activity Assay Kit is an ideal choice to perform routine protease isolation assays or for identifying the presence of contaminating proteases in protein samples. (stratech.co.uk)
Ubiquitin-specific proteases (USPs) are the largest DUB in all subfamilies, of which USP7 is the most prominent and well characterized member [ 5 ]. (biomedcentral.com)

DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)
Mechanistically, we show that RNF168-generated mUb-H2A recruits BARD1 through a BRCT domain ubiquitin-dependent recruitment motif (BUDR). (nih.gov)

Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene. (wikipedia.org)
Among the various genetic metabolic disorders, Angelman syndrome (AS) has attracted considerable attention due to the abnormal expression of the ubiquitin-protein ligase E3A (UBE3A) gene ( 1 ). (spandidos-publications.com)
The human UBE3A gene encodes an E3 ubiquitin ligase, which exhibits three known protein subtypes ( 1 , 8 ). (spandidos-publications.com)
Description of the protein which includes the UniProt Function and the NCBI Gene Summary. (nih.gov)
FUNCTION: This gene encodes a member of the RING finger family of E3 ubiquitin-protein ligases. (utsouthwestern.edu)
Our lab focuses on investigating the structure, function, and regulation of proteins involved in cell signaling, epigenetics, and gene regulation. (bu.edu)
2021). Examination of the C. gigas kinome found several serine/threonine-protein kinases in eggs and embryos, with some gene expression changes in response to abiotic stress (Epelboin et al. (github.io)
This gene encodes a member of the U-box ubiquitin ligase family. (nih.gov)
Expression analysis of the gene encoding for the U-box-type ubiquitin ligase UBE4A in human tissues. (nih.gov)
Mutations in both alleles of the parkin gene will cause dysfunction in its activity although not all mutations result in loss of parkin E3 ligase activity [38]. (buyresearchchemicalss.net)

The long term goal of our research is to elucidate the molecular mechanisms by which proteins are targeted to specific and distinct compartments. (stanford.edu)
However, in the mid 1990s, other proteins were also found to accumulate in the abnormal muscle fibers, and molecular genetic studies revealed several chromosomal loci. (medscape.com)

Similarily, target proteins can also be covalently modified by ubiquitin-like-proteins (Ubls) such as SUMO . (baypat.de)

The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
Subsequently, the inhibitory proteins that sequester NF-κB in the cytoplasm are phosphorylated, ubiquitinated, and degraded in the proteasome. (iucc.ac.il)

Ubiquitin protein ligase E3A attaches a small marker protein called ubiquitin to proteins that should be degraded. (dict.cc)

To deplete a protein using Trim-Away, researchers can simply choose an antibody that binds to their protein of interest and deliver this antibody to cells by giving them a mild electric shock. (cam.ac.uk)
Signaling is initiated when the Wnt ligand binds to the Frizzled receptor on the cell membrane and the LDL receptor-associated protein 5/6 (LRP5/6) co-receptor. (frontiersin.org)

We envision that the ability to cytosolically deliver IgGs and degrade target proteins would have a transformative impact, since it would dramatically expand the pool of viable drug targets and provide a powerful new tool to study protein function and intracellular signaling. (alphathera.com)
It has recently been demonstrated that a native intracellular system exists whereby cytosolic IgG can naturally engage TRIM21 E3 ubiquitin ligase to degrade antibody-bound targets. (alphathera.com)
To date, VHL-based PROTACs have been successfully used to degrade over 20 target proteins. (musechem.com)

One unknown link in the activation of NF-κB was the ubiquitin ligase that catalyzes generation of the active p50 subunit from its p105 inactive precursor. (iucc.ac.il)

Her work has been particularly influential in characterizing ubiquitin -like proteins (UBLs), a class of proteins that are similar to ubiquitin, such as NEDD8. (dict.cc)

This "casting a wide net" approach enables the exploration of diverse conformations, maximizing the potential for formation of ternary complexes with the POI and E3 ligase. (musechem.com)

FAs are structures composed of clustered transmembrane proteins called integrins that bind to the extracellular matrix and link to the actin cytoskeleton and control cell migration, proliferation, survival and differentiation (Gardel et al. (bio2009.org)
A large pore is formed by transmembrane proteins. (tcdb.org)

In particular, we will discuss the modifications in intrinsic and extrinsic apoptotic pathways caused by proteins encoded by HPV early genes. (mdpi.com)
ARA55, ARA54, ARA70, BRCA1, and heat-shock proteins) may allow cells to become independent of androgens (intrinsic activation). (aacrjournals.org)

This RING domain interacts with associated proteins, including BARD1, which also contains a RING motif, to form a heterodimer. (wikipedia.org)
USP7 interacts with PLK1 protein through its PBD domain by catalytic activity. (biomedcentral.com)

Here we have determined the 2.2 A crystal structure of an intermediate of UbcH5b~ubiquitin (Ub) conjugate, which is assembled into an infinite spiral through the backside interaction. (rcsb.org)

Despite the exciting potential of this approach, direct inhibition of target proteins with antibodies is highly epitope-dependent and requires a stoichiometric amount of antibody to be delivered, with each antibody only able to inhibit up to two targets. (alphathera.com)
Ubiquitination is a post-translational modification involving the addition of ubiquitin proteins onto target proteins. (dict.cc)
Although the widespread use of target-focused libraries has led to the rapid expansion of novel chemistry as research tools in drug discovery to exploit many classes of drug target, the ubiquitin system still remains a largely untapped medicinal chemistry opportunity. (ddw-online.com)
In this article, we propose that chemical libraries which target the ubiquitin system are the missing keys to unlock the therapeutic potential of ubiquitin system drug discovery. (ddw-online.com)
The PROTAC thus acts as a bridge that brings the target of interest into close proximity with an E3 ubiquitin ligase (Fig 1). (cisbio.net)
Protein kinases have become one of the most important target classes for the development of more effective anticancer drugs. (cisbio.net)

The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. (nih.gov)

Proteins associated with FAs include the nonreceptor tyrosine kinases FAK and Src. (bio2009.org)
Higher expression of serine/threonine-protein kinases in mature female gonads (Dheilly et al. (github.io)
2017). Several serine/threonine-protein kinases contained DML in C. virginica (Venkataraman et al. (github.io)
The activated receptor transmits the signal through downstream proteins to activate different kinases. (iucc.ac.il)
However, over the same period protein kinases have rapidly become one of the most significant classes of drug targets for the pharmaceutical industry, with the global market for kinase therapies being about US$15 billion per annum in 2010 and this value is predicted to double by 2020 (3). (ddw-online.com)
Research on protein kinases is now reported to account for approximately 30% of the drug discovery programmes in the pharmaceutical industry and more than 50% of cancer research and development (3). (ddw-online.com)

ARAP2 associates with adaptor protein with PH domain, PTB domain and leucine zipper motifs 1 (APPL1) in endosomes (Chen et al. (bio2009.org)

BRCA1 and BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. (wikipedia.org)
The BRCA1 protein contains the following domains: Zinc finger, C3HC4 type (RING finger) BRCA1 C Terminus (BRCT) domain This protein also contains nuclear localization signals and nuclear export signal motifs. (wikipedia.org)
These domains encode approximately 27% of BRCA1 protein. (wikipedia.org)

We list the DNA repair genes and related E3 ligases. (bmbreports.org)
The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
Over two dozen proteins involved in protein import and membrane insertion, peroxins, encoded by PEX genes, have been characterized. (tcdb.org)

CHIP is an E3 ligase, recognizing Hsp70-bound substrates via the TPR binding domain and catalyzing their ubiquitination via the U-box domain (hexagon). (elifesciences.org)

Pex4p is a membrane protein that may facilitate cycling of Pex5p back to the cytosol. (tcdb.org)

During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
The ubiquitin ligase UBE4A inhibits prostate cancer progression by targeting interleukin-like EMT inducer (ILEI). (nih.gov)

An effective approach is to generate a PROTACs database containing linear alkyl linkers of varying lengths until the appropriate length and orientation between the POI and E3 ligase can be identified. (musechem.com)

Thus, this protein plays a role in transcription, and DNA repair of double-strand DNA breaks ubiquitination, transcriptional regulation as well as other functions. (wikipedia.org)
The net impact of nutritional regulation of protease activity among the thousands of species present in soil can be observed at the overall microbial community level as proteins are broken down in response to carbon, nitrogen, or sulfur limitation. (stratech.co.uk)
Our current focus is on understanding the function and regulation of deubiquitinases and RNA-modifying proteins, which are emerging as attractive therapeutic targets in several cancers. (bu.edu)

We also study the NPC1 protein that is essential for cholesterol transport in humans and can lead to Niemann Pick C disease when mutated. (stanford.edu)

AMPK inhibits mTORC1 by direct interaction or by indirect activation of the TSC2 protein. (baxkyardgardener.com)
The protein interaction of PLK1 and USP7 was detected by tandem affinity purification and high throughput proteomics, and further confirmed by co-immunoprecipitation, GST pull-down and protein co-localization. (biomedcentral.com)

Protein depletion is a powerful strategy to study protein function and treat disease. (cam.ac.uk)
This type of modification was thought to be important for TRIM21 function and also the function of other proteins within the TRIM protein family. (cam.ac.uk)
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)
The ribosomal proteins (RPs) are essential for ribosome assembly and function, and it has been verified that the abnormal expression of RPs was closely associated with tumorigenesis. (bvsalud.org)
Post-translational modifications change function of most proteins. (bmbreports.org)
We are also interested in advancing new chemical strategies to investigate PTMs and protein function. (bu.edu)
The process of "sortylation" provides a powerful tool to modify non-refoldable and multidomain proteins whilst retaining their physiological integrity and biological function. (baypat.de)
Specific protein function and abnormalities are discussed below with each LGMD. (medscape.com)

Anatomy1

Organisms1

Diseases1

Chemicals and Drugs28

Phenomena and Processes10

Information Science3

Degradation38

Enzyme16

Enzymes13

Covalent5

Conjugation2

Residues6

Chains8

Ubiquitylation9

Lysine3

Pathway6

Ubiquitination of the target1

Cellular12

Molecule5

Phosphorylation2

Abstract1

Anaphase-promoti3

Tumor3

Proteasome system2

Histone1

Vitro2

Proteolysis1

Cell's1

Complex8

Proteases6

RNF1682

Gene10

Molecular2

Covalently1

Inhibitory proteins2

Attaches1

Binds2

Degrade3

Subunit1

NEDD81

Ternary1

Transmembrane2

Intrinsic2

Interacts2

Conjugate1

Target6

Polyubiquitination1

Kinases6

Adaptor protein1

BRCA13

Genes3

Substrates via1

Facilitate1

Progression2

PROTACs1

Regulation3

Humans1

Interaction2

Function8