Ubiquitin ligase protein degradation. Medical search. Frequent questions

Surprisingly, the endogenous MKRN1 protein underwent proteasomal degradation during the late phase of HAdV-C5 infection in various human cell lines. (scilifelab.se)
Based on these data, we propose that the pVII protein binding promotes MKRN1 self-ubiquitination, followed by proteasomal degradation of the MKRN1 protein, in HAdV-C5-infected cells. (scilifelab.se)
This mutual interaction between the pVII and MKRN1 proteins may prime MKRN1 for proteasomal degradation, because the MKRN1 protein is efficiently degraded during the late phase of HAdV-C5 infection. (scilifelab.se)
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)
Nedd4-2 is an ubiquitin ligase that catalyses the ubiquitination of proteins, resulting in proteasomal degradation. (portlandpress.com)
however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. (thermofisher.com)
Cd did not affect the protein levels of Keap1, which is a repressor of the cytoplasmic Nrf2, or Cul-3, an E3 ligase involved in the proteasomal degradation of Nrf2. (cdc.gov)

Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex. (nih.gov)
Vacuolar protein sorting 23A (VPS23A), a key component of the endosomal sorting complex required for transport I, mediates the entry of ubiquitinated ABA receptors into the vacuole for degradation. (phys.org)
Siah mediates its E3 ubiquitin ligase activity by directly binding to its substrates ( 4 ) or by acting as the essential RING domain subunit of a larger E3 complex ( 5 ) and can form homodimers and heterodimers. (aacrjournals.org)
E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. (nih.gov)
Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. (nih.gov)
Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins. (wikigenes.org)

Therefore, the level of ubiquitination of proteins must be finely regulated. (phys.org)

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. (mdpi.com)
Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. (mdpi.com)
In recent years, studies have found that ubiquitination mediated protein degradation plays an important role in regulating the ABA signaling pathway. (phys.org)
The E3 ubiquitin ligase XBAT35.2 can ubiquitinate and modify VPS23A to promote its entry into the 26S proteasome for degradation, thereby positively regulating the ABA signaling pathway. (phys.org)
The Smad7 protein is negative regulator of the TGF-β signaling pathway, which is upregulated in patients with breast cancer. (cancerindex.org)

Previous research by other investigators, according to Yarden, has shown that BRCA1 is an ubiquitin E3 ligase enzyme. (georgetown.edu)
In addition, the deubiquitinating enzyme USP13 reduces the substrate degradation activity of Siah proteins ( 11 ). (aacrjournals.org)
They found fifty percent less fat [triglycerides] in these cells in the BCAA mice, and much greater activity in the molecules that are involved in fat burning, such as the fat sensor PPAR-alpha, the enzyme COT-1 and the uncoupling proteins 2 and 3. (ironmagazine.com)
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)

In this study, we show that the HAdV-C5 histone-like core protein pVII binds to and promotes self-ubiquitination of a cellular E3 ubiquitin ligase named MKRN1. (scilifelab.se)
This protein binds with p53 and promotes the ubiquitin-mediated proteosomal degradation of p53. (wikipedia.org)
The protein encoded by this gene is a nuclear protein that binds the E3 ubiquitin ligase SMURF2. (cancerindex.org)

In particular, the proteins produced from the genes associated with 3-M syndrome are thought to help regulate proteins involved in the body's response to growth hormones, although their specific role in this process is unknown. (medlineplus.gov)
Yarden's lab discovered that BRCA1 targets two specific proteins cyclin B and Cdc25c, which are the "keeper genes" that regulate the G2/M checkpoint - the last checkpoint a cell has to go through before it divides. (georgetown.edu)
Humans have 2 Siah proteins, Siah1 and Siah2, derived from the SIAH1 and SIAH2 genes, respectively. (aacrjournals.org)
This heterodimer of HIF activates genes that encode for proteins such as vascular endothelial growth factor (VEGF) and erythropoietin, proteins that are both involved in angiogenesis. (standardofcare.com)
The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. (springer.com)
The discovery of the antioxidant response element (ARE) have led to the conclusion that the battery of genes, including glutamate-cysteine ligase (GCL), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HMOX1) is regulated through Nrf2 binding to this consensus binding sequence [ 3 ]. (springer.com)
Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. (bioone.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)
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)
Transcription factor Nrf2 is a key regulator of genes encoding phase II detoxification enzymes and antioxidant proteins in response to environmental chemical insults. (cdc.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)
The identification of pathogenic mutations within prion-like domains (PrLDs) of the RNA-binding proteins hnRNPA2B1 and hnRNPA1 add to our understanding of how mutations in these proteins lead to degenerative disease, and highlight the potential importance of PrLDs in degenerative diseases of the nervous system, muscle and bone. (natureasia.com)
With inherited diseases such as cystic fibrosis, mutations in the CFTR gene produce a protein that remains functional but is subject to excessive ubiquitination, leading to its rapid degradation via the proteasome. (businesswire.com)
In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site. (standardofcare.com)
Most of these mutations substitute one protein building block (amino acid) for another amino acid in the cullin-7 protein or result in a cullin-7 protein that is abnormally short and nonfunctional. (medlineplus.gov)
Scope includes mutations and abnormal protein expression. (cancerindex.org)

Ubiquitylation is regulated by enzymes that add (E3 ubiquitin ligases) or subtract (deubiquitylating enzymes) ubiquitin from substrates. (upenn.edu)
Excess ubiquitination is also a feature of cancer, where E3 ubiquitin ligases - enzymes that add ubiquitin to proteins - are frequently upregulated or amplified, driving the degradation of tumor suppressor proteins. (businesswire.com)

UBE2N promotes degradation of cIAP1 induced by cIAP1 ligands and subsequent cancer cell apoptosis. (nature.com)
Fig. 2: UBE2N promotes degrader-induced cIAP1 degradation and apoptosis. (nature.com)
It promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. (researchandmarkets.com)
C11orf54 promotes DNA repair via blocking CMA-mediated degradation of HIF1A. (nih.gov)
E1B-55K-Mediated Regulation of RNF4 SUMO-Targeted Ubiquitin Ligase Promotes Human Adenovirus Gene Expression. (tum.de)
Under normal conditions, Keap1 promotes ubiquitination and eventual degradation of Nrf2. (springer.com)

The cullin-7 protein plays a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system. (medlineplus.gov)
The ubiquitin-proteasome system helps regulate the level of proteins involved in several critical cell activities such as the timing of cell division and growth. (medlineplus.gov)
Ubiquitin Proteasome System Current Insights into Mechanism Cellular Regu. (intechopen.com)
Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (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)
Until now, it has not been possible to inhibit the ubiquitin-proteasome system in a target-selective manner. (businesswire.com)
Many viruses encode their own E3 ligases and deubiquitinases to coopt the ubiquitin-proteasome system as part of their life cycles. (businesswire.com)
The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. (medlineplus.gov)
Myostatin binding to type IIB activin receptor (ActRIIB) on muscle surface induces the recruitment and activation of activin receptor-like kinase 5 (ALK5), and eventually leads to forkhead box O3 (FoxO3a)-dependent transcription to promote muscle protein breakdown via the ubiquitin-proteasome system ( 23 ). (spandidos-publications.com)
PROTACs) are bifunctional small molecules, that harness the Ubiquitin Proteasome System (UPS) to selectively degrade target proteins within cells. (tocris.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)
However, bortezomib blocks all protein proteolysis by the proteasome without discrimination, causing various systemic toxicities and the development of resistance ( 1 ). (aacrjournals.org)
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)
Bio-IT World Disease treatment through targeted protein degradation takes a range of approaches: from small molecules similar to thalidomide that act as "molecular glue" degraders to more advanced "beyond rule of 5" proteolysis-targeting chimeras (PROTACs) with bifunctional moieties that encourage protein interaction with its E3 ubiquitin ligase. (bio-itworld.com)
Proteolysis targeting chimera consist of a target protein ligand connected via a linker to an E3 ligand. (bvsalud.org)

Specifically, cullin-7 helps assemble a complex called an E3 ubiquitin ligase, which tags the unneeded proteins for degradation. (medlineplus.gov)
Cullin-7 helps assemble a complex known as an E3 ubiquitin ligase. (medlineplus.gov)

The latest report E3 Ubiquitin Protein Ligase Mdm2 - Pipeline Review, H1 2020, outlays comprehensive information on the E3 Ubiquitin Protein Ligase Mdm2 (Double Minute 2 Protein or Hdm2 or Oncoprotein Mdm2 or p53 Binding Protein Mdm2 or MDM2 or EC 6.3.2. (researchandmarkets.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)
Her laboratory worked to discover which proteins BRCA1 is targeting with ubiquitin and how that activity might help attenuate cell division in response to DNA damage - a function that is important for maintaining genomic integrity and suppressing tumor growth. (georgetown.edu)
Download DNA or protein sequence, view genomic context and coordinates. (yeastgenome.org)

Human Adenovirus Infection Causes Cellular E3 Ubiquitin Ligase MKRN1 Degradation Involving the Viral Core Protein pVII. (scilifelab.se)
Here we report the identification of several cellular proteins interacting with the precursor pVII protein. (scilifelab.se)
We show that the cellular E3 ubiquitin ligase MKRN1 is a novel precursor pVII-interacting protein in HAdV-C5-infected cells. (scilifelab.se)
We combine this information with genetic, cellular and biochemical approaches to define how ubiquitin enzymes regulate immune cell biology. (upenn.edu)
The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
Oxidative stress generated during such stressful conditions may damage DNA and proteins, and as a consequence the cellular processes are disturbed. (springer.com)
Enhanced mTORC1 signaling and protein synthesis in pathologic α-synuclein cellular and animal models of Parkinson's disease. (neurotree.org)
In cellular environment protein abundance and half-life are determined by ubiquitin-proteasomal system. (lu.se)

E3 Ubiquitin Protein Ligase Mdm2 (Double Minute 2 Protein or Hdm2 or Oncoprotein Mdm2 or p53 Binding Protein Mdm2 or MDM2 or EC 6.3.2. (researchandmarkets.com)
E3 ubiquitin-protein ligase Mdm2 is a protein encoded by the MDM2 gene. (researchandmarkets.com)
The report provides a snapshot of the global therapeutic landscape for E3 Ubiquitin Protein Ligase Mdm2 (Double Minute 2 Protein or Hdm2 or Oncoprotein Mdm2 or p53 Binding Protein Mdm2 or MDM2 or EC 6.3.2. (researchandmarkets.com)
The report reviews latest news and deals related to E3 Ubiquitin Protein Ligase Mdm2 (Double Minute 2 Protein or Hdm2 or Oncoprotein Mdm2 or p53 Binding Protein Mdm2 or MDM2 or EC 6.3.2. (researchandmarkets.com)
Identify and understand the targeted therapy areas and indications for E3 Ubiquitin Protein Ligase Mdm2 (Double Minute 2 Protein or Hdm2 or Oncoprotein Mdm2 or p53 Binding Protein Mdm2 or MDM2 or EC 6.3.2. (researchandmarkets.com)

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)
This complex tags damaged and excess proteins with molecules called ubiquitin. (medlineplus.gov)
Keap1 is a cysteine-rich protein, known to be anchored to actin cytoskeleton [ 5 ], serving as an adaptor protein for the Cul3-dependent E3 ubiquitin ligase complex. (springer.com)
Membrane proteins must be threaded co-translocationally into the lipid bilayer to become membrane-integrated, often with complex topologies and typically form hetero- or homo- oligomers. (stanford.edu)
This highly complex 'protein biogenesis' process is assisted by a diverse network of folding catalysts and protein-modifying enzymes and is scrutinized by molecular chaperones and other 'quality control' factors which ensure that only correctly folded and assembled proteins exit the ER and proceed to distal compartments of the secretory pathway. (stanford.edu)
Upon binding, this complex translocates to the cytoplasm, where it interacts with TGF-beta receptor type-1 (TGFBR1), leading to the degradation of both the encoded protein and TGFBR1. (cancerindex.org)
A luminal surveillance complex that selects misfolded glycoproteins for ER-associated degradation. (wikigenes.org)
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)

Fig. 6: Generality of UBE2N-mediated (neo-)substrate degradation. (nature.com)

Once activated, NF-κB leads to upregulation of MuRF1, a ubiquitin ligase involved in degradation of muscle proteins. (jci.org)
Atrogin1 and muscle RING-finger 1 (MuRF1) are two important muscle-specific ubiquitin ligases that are induced in almost all types of muscle wasting ( 28 - 30 ). (spandidos-publications.com)

Fig. 5: UBE2N and UBE2D cooperatively assemble branched ubiquitin chains onto cIAP1 in vitro. (nature.com)

RING finger and CHY zinc finger domain-containing protein 1 is a protein that in humans is encoded by the RCHY1 gene. (wikipedia.org)
Siah proteins, evolutionarily conserved E3 RING zinc finger ubiquitin ligases, have recently been implicated in various cancers and show promise as novel anticancer drug targets. (aacrjournals.org)

Mechanistically, RNF8 acted as a negative regulator of Notch signaling by ubiquitylating the active NOTCH1 protein (N1ICD), leading to its degradation. (jci.org)

Molecular glues and targeted protein degraders are changing the landscape of drug discovery. (cas.org)
In short, this was an engaging panel that highlights future opportunities with molecular glues, targeted protein degraders, and the treatment of diseases with high unmet needs moving forward. (cas.org)

Degradation of neo-substrates directed by cIAP1-recruiting PROTACs also depends on UBE2N. (nature.com)

Human adenoviruses (HAdVs) are common human pathogens encoding a highly abundant histone-like core protein, VII, which is involved in nuclear delivery and protection of viral DNA as well as in sequestering immune danger signals in infected cells. (scilifelab.se)
Furthermore, in estrogen receptor (ER)-positive breast cancer cells, estrogen increases Siah2 levels, resulting in degradation of the nuclear receptor corepressor 1 (N-CoR) and a reduction in N-CoR-mediated repressive effects on gene expression, thus promoting cancer growth ( 12 ). (aacrjournals.org)
Spatially regulated ubiquitin ligation by an ER/nuclear membrane ligase. (wikigenes.org)

The ubiquitin code is a critical determinant of the fate of substrates. (nature.com)
We are now poised to define how cullin ligases form distinct ubiquitin complexes in T cells or other immune cells, and the unique set of substrates targeted by these complexes. (upenn.edu)
Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (intechopen.com)
Ubiquitin ligases recognize a highly specific peptide motif (degron) and transfer polyubiquitin chains to their respective substrates that eventually lead to degradation of the target protein by proteasome. (lu.se)

The protein encoded by this gene has ubiquitin-protein ligase activity. (wikipedia.org)

Siah proteins have been described to be both oncogenic and tumor suppressive in a variety of patient cohort studies and animal cancer models. (aacrjournals.org)

Robust cullin-RING ligase function is established by a multiplicity of poly-ubiquitylation pathways. (nature.com)
We use systems biology approaches to define changes in ubiquitylation as activation states change, and to identify ubiquitin ligases that regulate immune cell fate. (upenn.edu)
pVHL directs the ubiquitylation of HIF1A, ensuring that this protein will be degraded by the proteasome. (standardofcare.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)

Bifunctional molecules that are designed to recruit E3 UBIQUITIN LIGASE to a specific target protein. (bvsalud.org)

Stablix's RESTORED platform generates heterobifunctional small molecules (RESTORACS) that recruit deubiquitinase enzymes to remove ubiquitin from targeted proteins and consequently stabilize or increase target protein levels and activity. (businesswire.com)

Mitogen-activated protein kinase (MAPK) p38 phosphorylates Siah2 under hypoxic conditions, causing it to relocalize to the cytoplasm and subsequently increases its ubiquitin-targeted degradation activity ( 10 ). (aacrjournals.org)

E3 ligases consist of a large family of more than 600 proteins ( 3 ), and a few E3 ligases have been classified based on their conserved structural domains (e.g. (bmbreports.org)
They consist of three covalently linked components: an E3 ubiquitin ligase ligand, a linker and a ligand for the target protein of interest. (tocris.com)

Both proteins were ubiquitinated in the cytoplasm. (cdc.gov)

It inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. (researchandmarkets.com)
XIAP, X-linked mammalian inhibitor of apoptosis protein. (rupress.org)
The X-linked mammalian inhibitor of apoptosis protein (XIAP) has been shown to bind several partners. (rupress.org)
To determine which of these interactions are required for it to inhibit apoptosis, we generated point mutant XIAP proteins and correlated their ability to bind other proteins with their ability to inhibit apoptosis. (rupress.org)

The activity of G-protein-coupled receptors is not limited to the cell surface. (natureasia.com)

Guangchao Liu et al, The deubiquitinases UBP12 and UBP13 integrate with the E3 ubiquitin ligase XBAT35.2 to modulate VPS23A stability in ABA signaling, Science Advances (2022). (phys.org)

Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
Under homeostatic conditions, Nrf2 is rapidly degradated through a Keap1-dependent, ubiquitin-26S proteasome pathway. (cdc.gov)
In MEF cells with wild type Nrf2 and mouse hepa 1c1c7 cells, Cd increased the Nrf2 protein level but not the Nrf2 mRNA level dose-dependently. (cdc.gov)
Cd stabilized the Nrf2 protein by inhibiting the Keap1/CuI3dependent ubiquitination and 26S proteasomal turnover of Nrf2. (cdc.gov)

Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them. (medlineplus.gov)

Proteins synthesized at the ER are subject to covalent modifications that include N- and O-glycosylation, disulfide bond formation, and in some cases, proline and lysine hydroxylation. (stanford.edu)

In addition, we show that measles virus and vesicular stomatitis virus infections reduce the MKRN1 protein accumulation in the recipient cells. (scilifelab.se)
Since MKRN1 protein accumulation is also reduced in measles virus- and vesicular stomatitis virus-infected cells, our results signify the general strategy of viruses to target MKRN1. (scilifelab.se)
Immune cells must continually respond to external stimuli, and adjust their levels of key regulatory proteins, to transition between poised and active states. (upenn.edu)
To accomplish this, immune cells can increase protein production, modify existing proteins, or change their rate of protein degradation. (upenn.edu)
Our recent work has employed systems biology approaches in which we intrgrated transcriptome, proteome and ubiquitome information to identify Cullin E3 ubiquitin ligases that are particularly active as T cells transition from resting to activated states. (upenn.edu)
The paper shows that in response to DNA damage, BRCA1 is responsible for tagging these two proteins to stop the cells from dividing so repair can occur," Yarden said. (georgetown.edu)
Second, a suite of biochemical and functional assays is used to monitor the ubiquitination and functional status of target proteins in cells. (businesswire.com)
uncoupling proteins boost the heat production in cells. (ironmagazine.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)
Transcription of nhr-67 is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. (elifesciences.org)
In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. (elifesciences.org)
We combine biophysical and structural methods (e.g., cryo-EM), protein engineering, and in vivo approaches to understand how enveloped viruses infect host cells and elicit antigen-specific immune responses. (stanford.edu)
Currently we are identifying crucial proteins in blood forming stem cells that are regulated by ubiquitin signaling. (lu.se)
Since each ubiquitin ligase can recognize its target proteins through a specific degron, we are interested in delineating ubiquitin ligase-target protein interactions that are triggered by differentiation stimulus in stem cells. (lu.se)

A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies. (wikigenes.org)

The therapeutic value of augmenting protein stabilization has also been demonstrated with proteasome inhibitors. (businesswire.com)
In these studies, proteasome inhibitors were able to increase levels of deficient proteins across a range of targets and organ systems. (businesswire.com)
However, because proteasome inhibitors globally inhibit protein degradation in a non-specific manner, their use outside of oncology is limited by poor tolerability, highlighting the need for targeted approaches. (businesswire.com)
E3 ubiquitin ligases are therefore a more specific and effective target for drug development in comparison with general proteasome inhibitors to reduce treatment side effects and increase efficacies ( 1 ). (aacrjournals.org)

Many inherited and acquired diseases are caused by insufficient levels of specific proteins. (businesswire.com)

In particular, cullin-7 is thought to help regulate proteins involved in the body's response to growth hormones, although its specific role in this process is unknown. (medlineplus.gov)
miRNAs regulate proteins expressions by arresting or degrading the mRNAs. (cancerindex.org)

incorporates an E3 ligase ligand plus a PEG5 linker with terminal amine ready for conjugation to a target protein ligand. (tocris.com)

The proteasome controls protein abundance within the cell through proteolytic degradation of unneeded or damaged proteins. (aacrjournals.org)
We further demonstrate a role for the E3 ligase MARCH6 in regulating triacylglycerol biosynthesis, thereby influencing LD abundance and PLIN2 stability. (stanford.edu)
Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. (yeastgenome.org)
Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein. (yeastgenome.org)

The molecular details of how protein VII acts as a multifunctional protein have remained to a large extent enigmatic. (scilifelab.se)
Dr. Ebert started off with discussing some of the natural molecular glues such as Cyclosporin and molecular glues that do not utilize the E3 ligase for protein destruction, such as FK-506. (cas.org)
A Canadian team shares a new mechanism of action for remdesivir, data science groups have computed consensomes (gene expression in the virus) and interactomes (potential molecular mechanisms of pathogenesis) and cryoEM images the spike protein. (bio-itworld.com)

Learn more about their rise in oncology, inflammatory, and immune disease treatment through trends, protein targets, scientific mechanisms, and more in our latest article . (cas.org)

The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)

This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth. (medlineplus.gov)
Classes for this protein according to Protein ANalysis THrough Evolutionary Relationships (PANTHER) Classification System. (nih.gov)
This sheds light upon the role of the Smad7 protein in this system. (lu.se)

NSs Protein of Sandfly Fever Sicilian Phlebovirus Counteracts Interferon (IFN) Induction by Masking the DNA-Binding Domain of IFN Regulatory Factor 3. (tum.de)
Little is known about the upstream regulatory mechanisms of Siah proteins. (aacrjournals.org)

To explore this question, researchers from XIE Qi's team at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences found deubiquitinases ubiquitin-specific protease 12 (UBP12) and UBP13 are the interacting proteins of VPS23A via performing a screening assay. (phys.org)

Co-founders Dr. Colecraft and Scott Kanner, Ph.D., developed an approach to selectively recruit deubiquitinases (DUBs) to proteins of interest. (businesswire.com)

This mutation replaces the amino acid glutamine with a premature stop signal in the instructions for making the cullin-7 protein (written as Gln1553Ter or Q1553X), leading to production of an abnormally short protein. (medlineplus.gov)

Hence, even though UBP12 and UBP13 stabilize VPS23A, they could also promote the degradation of VPS23A under ABA treatment. (phys.org)

Tagging' a protein with ubiquitin is a post-translational modification that can improve interactions between proteins to promote signaling, or initiate protein degradation. (upenn.edu)

The effects of branched-chain amino acid granules on the accumulation of tissue triglycerides and uncoupling proteins in diet-induced obese mice. (ironmagazine.com)
Synthetic peptide taken within amino acid region 390-440 on human Parkin protein. (thermofisher.com)

Ubiquitin ligases are often inactive and their activation comes from external stimuli. (lu.se)

Stablix possesses a first-in-category platform that can restore protein stability and function in a target-selective manner," said Carlo Rizzuto, Ph.D., partner at Versant and acting CEO of Stablix. (businesswire.com)
Ubiquitination of substrate proteins can determine their protein activity, subcellular localization and even protein stability. (phys.org)
A series of biochemical experiments demonstrated that UBP12 and UBP13 can deubiquitinate VPS23A and maintain the protein stability of VPS23A. (phys.org)

This approach 'sticks' proteins of interests to E3 ubiquitin ligases of the ubiquitin-proteasome pathway, which helps with protein turnover and removes excess or damaged proteins within the body. (cas.org)

Anatomy25

Organisms14

Diseases4

Chemicals and Drugs120

Analytical, Diagnostic and Therapeutic Techniques and Equipment22

Phenomena and Processes67

Disciplines and Occupations1

Information Science3

Health Care3

Proteasomal degradation7

Mediates6

Ubiquitination of proteins1

Signaling pathway5

Enzyme4

Binds3

Genes12

Mutations6

Enzymes that add2

Promotes6

Proteasome system10

Proteolysis5

Helps assemble a complex2

20201

Genomic3

Cellular8

MdM25

Complex8

Substrate degradation1

MuRF12

Assemble1

Zinc finger2

RNF81

Degraders2

PROTACs1

Nuclear3

Substrates4

Encoded by this gene1

Oncogenic1

Ubiquitylation4

Bifunctional1

Small molecules1

Mitogen-activa1

Consist2

Cytoplasm1

Apoptosis4

Receptors1

Modulate1

Nrf24

Degrade1

Covalent1

Cells14

Membrane1

Inhibitors4

Specific proteins1

Regulate proteins2

Target protein ligand1

Abundance4

Molecular3

Targets1

Cyclin2

System3

Regulatory2

Protease1

Selectively1

Cullin-7 protein1

Stabilize1

Interactions1

Amino acid2

External stimuli1

Stability3

Excess1