Atpase protein degradation. Medical search. Frequent questions

The proteasome is a sophisticated ATP-dependent molecular machine responsible for protein degradation in all known eukaryotic cells. (rcsb.org)
Component of the lid subcomplex of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. (joplink.net)
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)
The proteasome is the major engine of protein degradation in all eukaryotic cells. (harvard.edu)
Proteasome 26S subunit, ATPase gene (PSMC) family members are well reported to be involved in protein degradation. (tmu.edu.tw)
A multiprotein ATPase complex required for the efficient dislocation of ER-lumenal degradation substrates, and their subsequent proteolysis by the proteasome. (yeastgenome.org)
Eukaryotic cells use the ubiquitin proteasome system to eliminate misfolded proteins from diverse subcellular compartments to maintain protein homeostasis. (rupress.org)
Once polyubiquitinated, soluble proteins are readily targeted to the proteasome. (rupress.org)
However, the degradation of proteins in lipid bilayer or membrane-encircled organelles requires additional steps because the membranes render these substrates, at least in part, inaccessible to the ubiquitin proteasome system. (rupress.org)
During this process, the hexameric barrel-like ATPase p97/Cdc48, assisted by an array of cofactors, uses the energy from ATP hydrolysis to extract polypeptides from the membranes for targeting to the proteasome. (rupress.org)
The study revealed four short-lived proteins (Fzo1, Mdm34, Msp1, and Tom70) whose rapid turnover depends not only on the proteasome but also on Cdc48. (rupress.org)
Many of the observed effects of VCP inhibition differed from the effects triggered by proteasome inhibition or by protein misfolding. (ox.ac.uk)
The ubiquitin-proteasome and autophagy-lysosome are the two major cellular degradation systems found in eukaryotic cells and organisms. (encyclopedia.pub)
The ubiquitin-proteasome pathway mainly relies on the 26S proteasome for the final degradation of its substrates [ 3 ] . (encyclopedia.pub)
Further inhibition of the 26S proteasome leads to accumulation of preproteins, supporting a connection between the ubiquitin-proteasome system (UPS) and preprotein degradation. (slub-dresden.de)
The mutation of the regulatory proteasome subunit Rpn8A in the plastid protein import mutant 2 (ppi2) background leads to partial rescue of the ppi2 plastid phenotype. (slub-dresden.de)

The a subunit, which controls cellular targeting of V-ATPases, is expressed as four isoforms in mammalian cells (a1-a4). (tufts.edu)
These studies suggest that human breast tumor cells employ particular a subunit isoforms to target V-ATPases to the plasma membrane, where they aid in tumor cell invasion. (tufts.edu)
Some of the proteotoxic effects of VCP depletion depended on the eIF2α phosphatase, protein phosphatase 1 regulatory subunit 15A (PPP1R15A)/PP1c, but not on mTORC1, although there appeared to be cross-talk between them. (ox.ac.uk)
subunit alpha of MPP mitochondrial signal peptidase heterodimer","protein_coding" "Zm00001e017599_P001","No alias","Zea mays","Protein disulfide isomerase-like 2-2 OS=Oryza sativa subsp. (ntu.edu.sg)

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)
Valosin-containing protein (VCP, also p97, or Cdc48p in yeast) is an evolutionarily conserved, homo-hexameric, ubiquitin-selective, AAA-ATPase that functions in numerous ubiquitin-dependent protein quality control pathways. (portlandpress.com)
p97/VCP (valosin-containing protein) is a cytosolic AAA (ATPase associated with various cellular activities) essential for retrotranslocation of misfolded proteins during ERAD [ER (endoplasmic reticulum)-associated degradation]. (portlandpress.com)
Here we identify valosin-containing protein (VCP) as a regulator of p53-R273H by conducting immunoprecipitation-tandem mass spectrometry analysis. (aacrjournals.org)
P97 is also known as valosin-containing protein which plays important roles in regulating protein homeostasis [1]. (apexbt.com)
Nearly all ERAD substrates are ubiquitinated prior to their degradation and these ubiquitin chains provide a binding site for VCP (Valosin-Containing Protein). (eu.org)
Valosin-containing protein (VCP), also called p97, is a AAA+ ATPase that has been shown to be involved in endoplasmic reticulum-associated protein degradation (ERAD), mitochondria quality control and vesicle transport. (oncotarget.com)

Protein crowding induces membrane curvatures through an entropic mechanism. (portlandpress.com)
Crowding of asymmetric proteins results in an asymmetric lateral pressure across the membrane which can be used by cells in a number of biological processes involving membrane remodeling. (portlandpress.com)
Function of Plasma Membrane V-ATPases in Breast Tumor Cell Invasion. (tufts.edu)
V-ATPases are expressed in intracellular compartments, such as endosomes and lysosomes, where they participate in processes such as membrane trafficking and protein degradation. (tufts.edu)
The a3 and a4 isoforms target V-ATPases to the plasma membrane of osteoclasts and renal intercalated cells, respectively. (tufts.edu)
MCF10CA1a cells expressed higher levels of the a3 isoform and higher levels of plasma membrane V-ATPases relative to MCF10a cells, and knockdown of a3 (but not other isoforms) using isoform-specific siRNAs inhibits invasion of MCF10CA1a cells. (tufts.edu)
Importantly, overexpression of the a3 isoform in the parental MCF10a cells significantly increased both the level of plasma membrane V-ATPases and in vitro invasion. (tufts.edu)
To determine whether expression of V-ATPases at the plasma membrane is important in breast cancer cell invasion, we have employed an inhibitory antibody that selectively blocks plasma membrane V-ATPase activity. (tufts.edu)
Inhibition of plasma membrane V-ATPases is shown to significantly reduce invasion of MDA-MB231 cells. (tufts.edu)
gp78, an ERAD ubiquitin ligase, is one of the p97/VCP recruitment proteins localized to the ER membrane. (portlandpress.com)
Mitochondrial protein degradation is not triggered by loss of mitochondrial membrane potential or oxidative stress. (elifesciences.org)
C ) Loss of mitochondrial membrane potential or oxidative stress does not activate autophagy-dependent Tom70-GFP degradation. (elifesciences.org)
The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. (cipsm.de)
Dislocation of polypeptides from the mitochondrial outer membrane by the p97/Cdc48-Ufd1-Npl4 adenosine triphosphatase complex is essential for mitochondria-associated degradation and Parkin-mediated mitophagy. (rupress.org)
the degradation of ubiquitinated substrates embedded in the membrane then requires their dislocation into the cytosol, a reaction mediated by a conserved ATPase named p97 in mammals or Cdc48 in Saccharomyces cerevisiae ( Christianson and Ye, 2014 ). (rupress.org)
The purpose of this study was to explore the content variation of thylakoid membrane protein complexes and its relationship with light absorption, transformation and transfer in flag leaves of high-yield hybrid rice Liangyoupeijiu during senescence. (chinacrops.org)
The content changes of thylakoid membrane protein complexes were also investigated by Blue-Native polyacrylamide gel-electrophoresis (BN-PAGE). (chinacrops.org)
The results showed that chlorophyll content, photosynthesis and thylakoid membrane protein content of flag leaves rose and peaked at heading stage, then began to decline. (chinacrops.org)
YE Lu-Huan,SHEN Wei-Jun,ZHENG Bao-Gang,SONG Tao,CHEN Guo-Xiang,Lü Chuan-Gen. Changes of Photosynthetic Membrane Function and Protein Complexes in Flag Leaves of Liangyoupeijiu during Leaf Senescence[J]. Acta Agron Sin, 2013, 39(11): 2030-2038. (chinacrops.org)
Autophagy depends on core autophagy proteins which contribute to the initiation of autophagosome formation, the lipidation of the autophagosomal membrane protein Atg8/LC3/GABARAP, the fusion of the autophagosome to the lysosome, and finally, the degradation of the autophagosome with its cargo within the lysosomal lumen [ 7 ] . (encyclopedia.pub)
All such systems are multisubunit complexes with at least 3 dissimilar subunits embedded as a complex in the membrane (F 0 , a:b:c = 1:2:~12) and (usually) at least 5 dissimilar subunits attached to F 0 (F 1 , α:β:γ:δ:ε = 3:3:1:1:1 for F-type ATPases). (tcdb.org)
However, the fact that OsClpC3 protein appears mitochondrial/chloroplastic with equal probability and OsClpC4 a plasma membrane protein reflects functional diversity of this class. (biomedcentral.com)
Mcl1 antiapoptotic protein is produced by Mtb -infected alveolar macrophages and is important for interrupting apoptosis in infected macrophages by regulating the mitochondrial membrane and blocking the release of cytochrome C and DNA-degrading enzymes [ 7 ⎼ 9 ]. (ajgreenchem.com)
P97 is an AAA-ATPase involved in multiple cellular functions such as organelle membrane homotypic fusion and sorting of endosomal cargo. (apexbt.com)
VCP complexes are involved in many cellular processes, particularly in the endoplasmic reticulum (ER)‐associated degradation (ERAD) process for protein quality control, membrane trafficking, and DNA damage response. (eu.org)
ERAD enables ER processing to distinguish the properly and improperly folded proteins in the ER lumen and then extracts them through membrane channels (dislocation or retrotranslocation) in an energy-dependent manner for delivery to cytosolic proteasomes. (eu.org)
Phytochrome may indirectly affect K+-ATPase by affecting membrane permeability and substrate availability. (eurekamag.com)
In vitro exposure of erythrocytes to oxygen radical generating systems (such as H 2 O 2 , ascorbate/Fe 3+ , cumene hydroperoxide, tert-butyl hydroperoxide, etc.) was shown to induce lipid peroxidation, protein degradation, loss of deformability, an increase in osmotic fragility, membrane lipid bilayer perturbation, inhibition of enzymes and hemolysis [5-12]. (scirp.org)
[ 2 ] The MNK protein also became localized toward the basolateral membrane and increased copper transport. (medscape.com)
FIC1 is a P-type ATPase responsible for maintaining a high concentration of phospholipids in the inner hepatocyte membrane. (medscape.com)
The mechanism whereby the loss of FIC1 activity results in defective bile salts excretion is unknown, but it has been hypothesized that a mutation in this protein causes phospholipid membrane instability leading to reduced function of bile acid transporters. (medscape.com)
This suggests that in most patients with PFIC-2, the gene defect is sufficiently severe to produce no product or a protein that cannot be inserted into the canalicular membrane. (medscape.com)
In PFIC3, a mutation in the gene ABCB4 on chromosome 7q21 encodes the protein MDR3, which functions in the translocation of phosphatidylcholine across the canalicular membrane. (medscape.com)

Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. (elifesciences.org)
We find that inhibition of V-ATPase activity by concanamycin reduced in vitro invasion of MCF10CA1a cells, but not the parental MCF10a cells. (tufts.edu)
A ) Schematic illustration showing that loss of vacuolar acidity (2) through aging or concanamycin A (conc A)-mediated inhibition of the Vacuolar H + -ATPase (1) leads to loss of mitochondrial function (3) through an unknown mechanism. (elifesciences.org)
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)
Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97. (ox.ac.uk)
VCP inhibition had an impact on two key regulators of protein synthesis, eukaryotic initiation factor 2α (eIF2α) and mechanistic target of rapamycin complex 1 (mTORC1), and attenuated global protein synthesis. (ox.ac.uk)
However, a block on protein translation that was itself cytotoxic alleviated stress signaling and reduced cell death triggered by VCP inhibition. (ox.ac.uk)
Thus, cancer cell death following VCP inhibition was linked to inadequate fine-tuning of protein synthesis and activity of PPP1R15A/PP1c. (ox.ac.uk)
[ 8 ] Glucocorticoid excess may lead to muscle weakness via inhibition of protein synthesis, increased protein catabolism and altered carbohydrate metabolism. (medscape.com)

In mammals, this complex includes a hexamer of VCP/p97 (a cytosolic ATPase) and trimers of each of its cofactors UFD1L and NPL4 (NPLOC4) (e.g. a 6:3:3 stoichiometry). (yeastgenome.org)
CB-5083 could dose-dependently increase the cytosolic protein degradation in HEK293T, A549 and HCT116 cell lines [1]. (apexbt.com)

This review summarizes recent research on VCP that has uncovered surprising new ways that this ATPase is regulated, new aspects of recognition of substrates and novel pathways and substrates that utilize its activity. (portlandpress.com)
VCP identifies ubiquitylated substrates through numerous dedicated adaptor proteins and unfolds substrates by threading them through a central pore in the hexamer ( Figure 1 ). (portlandpress.com)
It is a substrate recognition domain which binds polypeptides, prevents protein aggregation, and catalyses refolding of permissive substrates. (embl-heidelberg.de)
first measured the half-life of endogenously tagged MOM proteins to identify substrates suitable for mechanistic characterization of this process. (rupress.org)
Considered to be the more selective of the two degradation systems, proteasomal substrates are largely composed of individual proteins, requiring large complexes to be disassembled before degradation can take place [ 4 ] . (encyclopedia.pub)
Autophagy substrates tend to be larger, including protein aggregates, organelles- either in their entirety or select portions, and invading pathogens. (encyclopedia.pub)
Although autophagy was historically considered to be a bulk degradation pathway, it is now universally accepted that it can be quite selective, with a wide range of substrates under its jurisdiction. (encyclopedia.pub)
It is intriguing that two seemingly independent degradation pathways, which have evolved largely different components and substrates, converge on the same PTM for cargo recognition. (encyclopedia.pub)

BACKGROUND: The VAT protein of the archaebacterium Thermoplasmaacidophilum, like all other members of the Cdc48/p97 family of AAAATPases, has two ATPase domains and a 185-residue amino-terminalsubstrate-recognition domain, VAT-N. VAT shows activity in protein foldingand unfolding and thus shares the common function of these ATPases indisassembly and/or degradation of protein complexes. (embl-heidelberg.de)
The eukaryotic proteins are more complicated than the bacterial enzyme complexes. (tcdb.org)

Additionally, SVIP (small p97/VCP-interacting protein), which contains a VIM in its N-terminal region, negatively regulates ERAD by uncoupling p97/VCP and Derlin1 from gp78. (portlandpress.com)
The ERAD (ER-Associated Degradation) mechanism acts as a protein quality control and removes these misfolded proteins. (eu.org)
Thus ERAD is essential for ER homeostasis and correct functioning by degrading misfolded proteins ( Hwang,2018 ). (eu.org)

In budding yeast, this complex includes Cdc48p, Npl4p and Ufd1p proteins. (yeastgenome.org)

At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. (harvard.edu)
Although many ClpP enzymes self-assemble into catalytically active homo-tetradecamers able to cleave small peptides, the Mycobacterium tuberculosis enzyme consists of discrete ClpP1 and ClpP2 heptamers that require a AAA+ partner and protein-substrate delivery or a peptide agonist to stabilize assembly of the active tetradecamer. (anl.gov)

F-type ATPases are found in eukaryotic mitochondria and chloroplasts as well as in bacteria. (tcdb.org)

We identify the vacuolar H + -adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD's asymmetric segregation. (elifesciences.org)
p97) is an essential regulator of protein degradation in multiple pathways and has emerged as a target for cancer therapy. (ox.ac.uk)

The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. (cipsm.de)
Plastid-specific ribosomal proteins (PSRPs) have been proposed to play roles in the light-dependent regulation of chloroplast translation. (cipsm.de)
Thus, depletion of VCP enzymatic activity triggers cancer cell death in part through inadequate regulation of protein synthesis and amino acid metabolism. (ox.ac.uk)

TRIP13 is a mammalian gene that encodes the thyroid receptor-interacting protein 13. (wikipedia.org)
The TRIP13 gene has been shown to interact with a variety of proteins and implicated in a few diseases, notably interacting with the ligand binding domain of thyroid hormone receptors, and may play a role in early-stage non-small cell lung cancer. (wikipedia.org)
Our method considers a variety of features including protein sequences, gene co-expression, functional association, and phylogenetic profiles. (nature.com)
Previous studies have shown that ClpB-cyt/HSP100 gene belongs to the group class I Clp ATPase proteins and ClpB-cyt/HSP100 transcript is regulated by heat stress and developmental cues. (biomedcentral.com)
Rice class I Clp ATPase gene family is constituted of 9 members. (biomedcentral.com)
The protein-centered research could not uncover all the gene regulatory and signaling pathways to sustain the healthy heart. (amegroups.org)
The emergence of non-protein-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and more recent long non-coding RNAs (lncRNAs), has shed a light on further dissecting the gene regulatory networks of the heart ( 3 , 4 ). (amegroups.org)
immunogenic differences in their surface M proteins and polymorphisms in the emm gene ( 1 ). (cdc.gov)
The Menkes gene is located on the long arm of the X chromosome at Xq13.3, and the gene product (ATP7A) is a 1500-amino acid P-type adenosine triphosphatase (ATPase) that has 17 domains - 6 copper binding, 8 transmembrane, a phosphatase, a phosphorylation, and an ATP binding. (medscape.com)
This gene encodes the protein FIC1, also known as ATP8B1. (medscape.com)

However, if either of these processes proceeds too slowly or fails, HSP70/HSPA1A can interact with the HSP40 co-chaperone protein and the CHIP/STUB1 Ubiquitin ligase (E3) to promote ubiquitination and degradation of the nascent polypeptide or denatured protein (3,4). (novusbio.com)

Ter94 in fly, CDC48 in yeast) is a hexameric multidomain protein belonging to the functionally highly diverse AAA+ (ATPases Associated with diverse cellular Activities) superfamily of proteins. (eu.org)

Mitochondrial proteins are degraded by autophagy in aged cells. (elifesciences.org)
C ) Loss of vacuolar acidity activates autophagy-dependent Tom70-GFP degradation. (elifesciences.org)
D ) Tom70-GFP was monitored for autophagy-dependent degradation using a GFP-cleavage assay in wild-type (WT) and the indicated mutant cells treated with concanamycin A (ConcA) for the indicated time (hr). (elifesciences.org)
Defective autophagy and lysosomal degradation are hallmarks of numerous neurodegenerative disorders. (fu-berlin.de)

We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates. (elifesciences.org)

In vitro: CB-5083 is a selective potent inhibitor of p97's second ATPase domain. (apexbt.com)
Discovery of a First-in-Class, Potent, Selective, and Orally Bioavailable Inhibitor of the p97 AAA ATPase (CB-5083)[J]. Journal of medicinal chemistry, 2015, 58(24): 9480-9497. (apexbt.com)
17-allylamino-17-demethoxygeldanamycin AZD9567 (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational switch which destabilizes client proteins and directs them towards proteosomal degradation. (biomasswars.com)

The quest for novel targeted protein degraders starts with discovery - finding and evaluating molecules that interact with both the target protein and the cellular degradation machinery, such as the E3 ligase pathway (Lee et al. (biognosys.com)
Recently, we applied TrueTarget in collaboration with researchers at the University of Cambridge to study the binding of novel activators of VCP/p97, a key component of the proteasomal protein degradation pathway and an exciting emerging target in a number of neurodegenerative diseases. (biognosys.com)

its stimulating effect on the immune system has been described and also the way it stimulates protein synthesis and inhibits proteic enzymatic degradation in the fibroblasts. (ageless.co.za)
The plant is responsiblefor increasing phospholipid synthesis in the blood, inhibiting ATPase in the brain and many other effects. (ageless.co.za)
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)
V-type ATPases may pump 2-3 H + per ATP hydrolyzed, and these enzymes cannot catalyze pmf-driven ATP synthesis. (tcdb.org)
The Endoplasmic Reticulum (ER) is an important eukaryotic cell organelle that has various functions, including the synthesis of proteins for export and quality control of nascent proteins. (eu.org)

Intramembrane protease RHBDL4 interacts with erlin complex to target unstable soluble proteins for degradation. (apexbt.com)

As an AAA+ ATPase, TRIP13 (and its PCH2 analog) forms homohexamers and interacts with ATP as an energy source. (wikipedia.org)
TRIP13/PCH2 also functions as a kinetochore protein that interacts with the silencing protein p31-Comet. (wikipedia.org)
V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. (elifesciences.org)

It reduces the degradation of ubiquitin-conjugated proteins in mammalian cells and permeable strains of yeast by the 26S complex without affecting its ATPase or isopeptidase activities. (xcessbio.com)

The K+-ATPase appeared to be strongly inhibited by Ca+2 and was subject to photoregulation by red and far red light (R and F) in vitro. (eurekamag.com)
Photoregulation of ATPase in vitro occurred only if R was given in vivo prior to extraction. (eurekamag.com)
The effects of eleven flavonoids on lipid peroxidation, protein degradation, deformability and osmotic fragility of human erythrocytes exposed in vitro to 10 mM H 2 O 2 for 60 min at 37˚C have been studied. (scirp.org)

Several cellular degradation processes have evolved to fill this need and their importance is illustrated through their conservation across evolution, and the pathology that ensues with their perturbance [ 1 ] [ 2 ] . (encyclopedia.pub)

VCP (P97, TERA) is an essential and abundant AAA-ATPase that mediates vital cellular activities with the cooperation of many cofactors. (eu.org)

In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). (bilkent.edu.tr)

Using the respective signal sequences cloned upstream to GFP/CFP reporter proteins and transient expression studies with onion epidermal cells, evidence is provided that rice ClpB-m and Clp-c proteins are indeed localized to their respective cell locations mitochondria and chloroplasts, respectively. (biomedcentral.com)

This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. (joplink.net)

The CDC48 N-terminal domain is a protein domain found in AAA ATPases including cell division protein 48 (CDC48), VCP-like ATPase (VAT) and N-ethylmaleimide sensitive fusion protein. (embl-heidelberg.de)
There are 6871 CDC48_N domains in 6866 proteins in SMART's nrdb database. (embl-heidelberg.de)
Taxonomic distribution of proteins containing CDC48_N domain. (embl-heidelberg.de)
The complete taxonomic breakdown of all proteins with CDC48_N domain is also avaliable . (embl-heidelberg.de)
Click on the protein counts, or double click on taxonomic names to display all proteins containing CDC48_N domain in the selected taxonomic class. (embl-heidelberg.de)

Abstract: The vacuolar H+ ATPases (V-ATPases) are a family of ATP-driven proton pumps that couple ATP hydrolysis with translocation of protons across membranes. (tufts.edu)

Targeting the AAA ATPase p97 as an Approach to Treat Cancer through Disruption of Protein Homeostasis[J]. Cancer cell, 2015, 28(5): 653-665. (apexbt.com)

Khaperskyy DA, Schmaling S, Larkins-Ford J MMID , McCormick C, Gaglia MM. Selective degradation of host RNA polymerase II transcripts by influenza A virus PA-X host shutoff protein. (tufts.edu)

Though the VCP and their binding partners are conserved in eukaryotes, the sequences that mediate their interactions are significantly different across organisms showing that evolution has established more than one way for these proteins to interact. (eu.org)
Identification of mosquito proteins that differentially interact with alphavirus nonstructural protein 3, a determinant of vector specificity. (cdc.gov)

Cereal endosperm is a short-lived tissue adapted for nutrient storage, containing specialized organelles, such as protein bodies (PBs) and protein storage vacuoles (PSVs), for the accumulation of storage proteins. (nature.com)
Together our data identified promising targets to be genetically engineered to modulate seed storage protein accumulation that have a growing role in health and nutritional issues. (nature.com)
Ageing leads to a gradual dysfunction of the proteostasis network and thus to proteome instability due to accumulation of damaged and/or misfolded proteins [ 2 ]. (hindawi.com)
Conversely, it is thought to protect against several neurodegenerative diseases that are caused by the accumulation of misfolded proteins (11,12). (novusbio.com)
These processes have remained conserved among species and failure of either one can result in the accumulation of toxic or damaged proteins and organelles, culminating in a number of severe pathologies including cancer, failure to thrive, degenerative diseases, and premature death [ 1 ] [ 2 ] . (encyclopedia.pub)
In the lung carcinoma cell line A549, CB-5083 led to accumulation of poly-ubiquitinated proteins. (apexbt.com)
In HCT116 cells, CB-5083 treatment resulted in accumulation of K48-ubiquitinated proteins at a higher molecular weight. (apexbt.com)

The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. (cipsm.de)
Heat Shock 70kDa Protein (HSP70), also known as Heat Shock 70kDa Protein 1A (HSPA1A), is a 641 amino acid (aa) member of the HSP70 family of molecular chaperones with a predicted molecular weight of 70 kDa. (novusbio.com)
HSP70/HSPA1A promotes the proper folding of nascent polypeptides and assists in the refolding of denatured proteins (2). (novusbio.com)

It remains elusive how conformational changes of the AAA-ATPase unfoldase in the regulatory particle (RP) control the gating of the substrate-translocation channel leading to the proteolytic chamber of the core particle (CP). (rcsb.org)
The mitochondria have their own chaperones and proteolytic enzymes that remove damaged or unfolded proteins [ 18 - 20 ]. (hindawi.com)
This process involves the formation of double membraned vesicles, known as autophagosomes, around a substrate or a cytoplasmic domain, and the subsequent delivery of these vesicles to the lysosome for proteolytic degradation (Figure 1). (encyclopedia.pub)

Even for Arabidopsis , known PPI data cover interactions with only about 34.55% of proteins. (nature.com)
The majority of Arabidopsis thaliana plastid proteins is nuclear encoded and has to be synthesized in the cytosol as preproteins. (slub-dresden.de)

Hardman et al found that insulin and estrogen increased the level of MNK mRNA and protein levels in the placenta. (medscape.com)
however, knockdown of AGO2 abrogated the S970D-induced mRNA degradation. (cdc.gov)
phosphorylation of S970 restricts this activity resulting in AGO2-mediated mRNA degradation. (cdc.gov)

Gate opening in the CP is thus regulated by nucleotide-driven conformational changes of the AAA-ATPase unfoldase. (rcsb.org)
Coordinated, stepwise conformational changes of the regulatory particle couple ATP hydrolysis to substrate translocation and regulate gating of the core particle, leading to processive degradation. (harvard.edu)

Together these two reports suggest that a neuronal V0a1-dependent degradation mechanism may be causally linked to Alzheimer pathology. (fu-berlin.de)
Furthermore, we discuss the potential significance of the discovery of the neuron-specific degradation mechanism in Drosophila for intracellular degradation defects in Alzheimer Disease. (fu-berlin.de)
Mass spectrometry proteomics is the perfect tool for this task, providing detailed data about target binding, degradation selectivity and mechanism of action in the early stages of drug development, as well as information about efficacy and safety in preclinical and clinical phases (Zhang et al. (biognosys.com)

The acid phosphatase activity was not subject to photoregulaton but its presence prevented further characterization of the K+-ATPase and its photoregulation. (eurekamag.com)

Vesicular ATPases are intracellular proton pumps that acidify autophagosomes and lysosomes. (fu-berlin.de)

Moreover, endosomal sorting complex required for transport (ESCRT)-related proteins and their transcripts are most abundant at early and mid-development. (nature.com)
Different class I Clp ATPase transcripts were noted to be cross-induced by a host of different abiotic stress conditions. (biomedcentral.com)

Quercetin and 3,5,7-trihydroxy-4'-methoxy flavone-7-rutinoside significantly protected erythrocytes against loss of deformability and increased osmotic fragility, indicating that the loss of erythrocyte deformability and the increase in osmotic fragility of erythrocytes exposed to H 2 O 2 are related to protein degradation rather than to lipid peroxidation. (scirp.org)

The aleurone layer plays essential roles during seed germination and mobilizes starch and SSP reserves in the starchy endosperm by releasing hydrolytic enzymes that are responsible for the degradation of stored nutrients in the endosperm 2 . (nature.com)
Sequence and structure analyses showed thatVAT-Nn is related to numerous proteins including prokaryotic transcriptionfactors, metabolic enzymes, the protease cofactors UFD1 and PrlF, andaspartic proteinases. (embl-heidelberg.de)
These proteins map out an evolutionary path fromsimple homodimeric transcription factors containing a single copy of theVAT-Nn repeat to complex enzymes containing four copies. (embl-heidelberg.de)

The histidine residue is the most common mutation site in Wilson disease, and this histidine residue is essential for the function of the Menkes ATPase, ATP7A. (medscape.com)

Rather than using conventional small molecules or antibodies that bind to a target and inhibit its function, targeted protein degradation directs harmful proteins for destruction by the cell's own degradation machinery. (biognosys.com)

CB-5083 IC50 analyses for p97 and mutants were conducted utilizing a standard NADH-based coupled kinetic ATPase assay. (apexbt.com)

Based on proteome annotation and a homology search, 94 proteins associated with the endomembrane system were identified that exhibited significant changes in abundance during grain development. (nature.com)
A proteome-wide comparison of ppi2 with the rpn8a ppi2 double mutant showed among other things increased abundance of photosynthetic proteins. (slub-dresden.de)

Caseinolytic peptidase P (ClpP), a double-ring peptidase with 14 subunits, collaborates with ATPases associated with diverse activities (AAA+) partners to execute ATP-dependent protein degradation. (anl.gov)

All copper-transporting ATPases have a histidine residue in the large cytoplasmic loop adjacent to the ATP-binding domain. (medscape.com)

Fail-safe degradation mechanisms are therefore required for the effective disposal of potentially toxic and harmful components and their recycling into building blocks needed for biosynthesis. (encyclopedia.pub)

ClpB-cyt/HSP100 protein acts as chaperone, mediating disaggregation of denatured proteins. (biomedcentral.com)
While expression of OsClpB-m was significantly less as compared to its cytoplasmic and chloroplastic counterparts in different tissues, this transcript showed highest heat-induced expression amongst the 3 ClpB proteins. (biomedcentral.com)
Distribution of ClpB proteins to different cell organelles indicates that their functioning might be critical in different cell locations. (biomedcentral.com)

Das helicale, hochgeladene DMIF1-Monomer hat eine N-terminale Targeting-Domäne, die den Transfer des im Zytoplasma gebildeten Precursors in die Mitochondrien bewirkt, wo das reife Protein durch Abspalten der Domäne nach einem modifizierten R-2-Motiv durch die Protease MPP entsteht. (tum.de)
Sterische Störung der Targeting-Domäne durch die Fusion an GFP führt zum Transfer in die pericentrosomale Region, wo das ungefaltete Protein in Aggresomen degradiert wird. (tum.de)
Das helicale, hochgeladene DMIF1-Monomer hat eine N-terminale Targeting-Domäne, die den Transfer des im Zytoplasma gebildeten Precursors in die Mitochondrien bewirkt, wo das reife Protein durch Abspalten d. (tum.de)
The helical, highly charged DMIF1 protein monomer contains an N-terminal targeting domain to transfer the precursor, synthesized in the cytoplasm, to mitochondria. (tum.de)
Sterical blocking of the targeting domain by the reporter protein GFP fused to DMIF1 N-terminus targets the protein to aggresomes in the pericentrosomal region, where the unfolded protein is degradated. (tum.de)

Evidence shows that TRIP13/PCH2 uses p31-Comet as an adaptor protein to convert C-Mad2 into O-Mad2. (wikipedia.org)
Garafalo SD, Luth ES, Moss BJ NEURO , Monteiro MI, Malkin E, Juo P. The AP2 clathrin adaptor protein complex regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans. (tufts.edu)

notably, integration of proteomics data with in situ subcellular microscopic analyses showed a high abundance of cytoskeleton proteins associated with acidified PBs at the early development stages. (nature.com)

Loss of vacuole function triggers mitochondrial protein degradation. (elifesciences.org)
Protein conformation is critically linked to function and often controlled by interactions with regulatory factors. (cipsm.de)
Cells express a pool of thousands of different proteins that need to be tightly controlled for proper cellular structure, organization, and function. (hindawi.com)

Anatomy30

Organisms13

Diseases3

Chemicals and Drugs127

Analytical, Diagnostic and Therapeutic Techniques and Equipment24

Phenomena and Processes57

Technology, Industry, Agriculture1

Information Science3

Health Care3

Proteasome17

Subunit4

Valosin-contain7

Membrane33

Inhibition9

Cytosolic2

Substrates8

Complexes2

ERAD3

Budding yeast1

Peptides2

Found in eukaryotic1

Regulator2

Regulation3

Gene10

Ubiquitination and degradation1

Superfamily1

Autophagy4

Acidification1

Inhibitor3

Pathway2

Synthesis5

Soluble proteins1

Interacts3

Mammalian cells1

Vitro3

Cellular degradation1

Mediates1

Proteasomal1

Mitochondria and chloroplasts1

Removing misfolded1

Cdc485

Vacuolar1

Homeostasis1

Selective1

Interact2

Accumulation7

Hsp703

Proteolytic3

Arabidopsis2

MRNA3

Conformational2

Mechanism3

Characterization1

Intracellular1

Transcripts2

Lipid1

Enzymes3

Mutation1

Directs1

Assay1

Proteome2

Subunits1

Histidine1

Biosynthesis1

ClpB3

Targeting5

Adaptor protein2

Abundance1

Function3