Cullin Proteins: A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.Ubiquitins: A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.SKP Cullin F-Box Protein Ligases: A subset of ubiquitin protein ligases that are formed by the association of a SKP DOMAIN PROTEIN, a CULLIN DOMAIN PROTEIN and a F-BOX DOMAIN PROTEIN.F-Box Proteins: A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Cell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Hominidae: Family of the suborder HAPLORHINI (Anthropoidea) comprising bipedal primate MAMMALS. It includes modern man (HOMO SAPIENS) and the great apes: gorillas (GORILLA GORILLA), chimpanzees (PAN PANISCUS and PAN TROGLODYTES), and orangutans (PONGO PYGMAEUS).Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Peptide Termination Factors: Proteins that are involved in the peptide chain termination reaction (PEPTIDE CHAIN TERMINATION, TRANSLATIONAL) on RIBOSOMES. They include codon-specific class-I release factors, which recognize stop signals (TERMINATOR CODON) in the MESSENGER RNA; and codon-nonspecific class-II release factors.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Software: Sequential operating programs and data which instruct the functioning of a digital computer.ArchivesBiological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Directories as Topic: Lists of persons or organizations, systematically arranged, usually in alphabetic or classed order, giving address, affiliations, etc., for individuals, and giving address, officers, functions, and similar data for organizations. (ALA Glossary of Library and Information Science, 1983)Ubiquitin-Protein Ligases: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.S-Phase Kinase-Associated Proteins: A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.Ubiquitination: The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.Calcineurin: A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.NFATC Transcription Factors: A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.Proteasome Endopeptidase Complex: A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.Host-Pathogen Interactions: The interactions between a host and a pathogen, usually resulting in disease.Systems Biology: Comprehensive, methodical analysis of complex biological systems by monitoring responses to perturbations of biological processes. Large scale, computerized collection and analysis of the data are used to develop and test models of biological systems.Proteomics: The systematic study of the complete complement of proteins (PROTEOME) of organisms.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.Meaningful Use: Using certified ELECTRONIC HEALTH RECORDS technology to improve quality, safety, efficiency, and reduce HEALTHCARE DISPARITIES; engage patients and families in their health care; improve care coordination; improve population and public health; while maintaining privacy and security.Proteome: The protein complement of an organism coded for by its genome.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Phenylmethylsulfonyl Fluoride: An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Aprotinin: A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)BoliviaBiotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.Microcystins: Cyclic heptapeptides found in MICROCYSTIS and other CYANOBACTERIA. Hepatotoxic and carcinogenic effects have been noted. They are sometimes called cyanotoxins, which should not be confused with chemicals containing a cyano group (CN) which are toxic.Templates, Genetic: Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.Science: The study of natural phenomena by observation, measurement, and experimentation.Reagent Kits, Diagnostic: Commercially prepared reagent sets, with accessory devices, containing all of the major components and literature necessary to perform one or more designated diagnostic tests or procedures. They may be for laboratory or personal use.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Fukushima Nuclear Accident: Nuclear power accident that occurred following the Tohoku-Kanto earthquake of March 11, 2011 in the northern region of Japan.Encephalitis Virus, Japanese: A species of FLAVIVIRUS, one of the Japanese encephalitis virus group (ENCEPHALITIS VIRUSES, JAPANESE), which is the etiological agent of Japanese encephalitis found in Asia, southeast Asia, and the Indian subcontinent.Encephalitis, Japanese: A mosquito-borne encephalitis caused by the Japanese B encephalitis virus (ENCEPHALITIS VIRUS, JAPANESE) occurring throughout Eastern Asia and Australia. The majority of infections occur in children and are subclinical or have features limited to transient fever and gastrointestinal symptoms. Inflammation of the brain, spinal cord, and meninges may occur and lead to transient or permanent neurologic deficits (including a POLIOMYELITIS-like presentation); SEIZURES; COMA; and death. (From Adams et al., Principles of Neurology, 6th ed, p751; Lancet 1998 Apr 11;351(9109):1094-7)Nuclear Power Plants: Facilities that convert NUCLEAR ENERGY into electrical energy.Cesium Radioisotopes: Unstable isotopes of cesium that decay or disintegrate emitting radiation. Cs atoms with atomic weights of 123, 125-132, and 134-145 are radioactive cesium isotopes.Radiation Monitoring: The observation, either continuously or at intervals, of the levels of radiation in a given area, generally for the purpose of assuring that they have not exceeded prescribed amounts or, in case of radiation already present in the area, assuring that the levels have returned to those meeting acceptable safety standards.Soil Pollutants, Radioactive: Pollutants, present in soil, which exhibit radioactivity.

Alternate choice of initiation codon produces a biologically active product of the von Hippel Lindau gene with tumor suppressor activity. (1/749)

The VHL tumor suppressor gene has previously been reported to encode a protein of 213 amino acid residues. Here we report the identification of a second major VHL gene product with an apparent molecular weight of 18 kD, pVHL18, which appears to arise from alternate translation initiation at a second AUG codon (codon 54) within the VHL open reading frame. In vitro and in vivo studies indicate that the internal codon in the VHL mRNA is necessary and sufficient for production of pVHL18. pVHL18 can bind to elongin B, elongin C, and Hs-CUL2. When reintroduced into renal carcinoma cells that lack a wild-type VHL allele, pVHL18 suppresses basal levels of VEGF expression, restores hypoxia-inducibility of VEGF expression, and inhibits tumor formation in nude mice. These data strongly support the existence of two distinct VHL gene products in VHL tumor suppression.  (+info)

Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer. (2/749)

D-type cyclins are important cell cycle regulators that promote cellular proliferation in response to growth factors by inactivation of the retinoblastoma protein (Rb). Cyclin D1 has been shown to be overexpressed in several cancer types and to act as an oncogene in breast cancers. As D-type cyclins are rate limiting for progression into S phase, the level at which they accumulate must be carefully regulated. Several mechanisms leading to overexpression of cyclin D1 have been reported including amplification, translocation and stabilization of the mRNA. Here, we present data showing elevated cyclin D1 protein in breast cancer samples in the absence of elevated mRNA level. Further, we found that in these cases, cyclin D3 protein also accumulates and that the coordinate increase in cyclin D1 and D3 occurs in 15% (7/47) of breast cancers. In addition we show that blocking the activity of the 26S proteosome results in the accumulation of cyclin D1 and D3, that both D-type cyclins are ubiquitinated and associate with Cul-1, a component of the SCF ubiquitin ligase complex. Finally, we show that the coordinated elevation of cyclin D1 and D3 is also observed in the breast cell line MCF-7 and demonstrate that the degradation of cyclin D1 and D3 is deficient in this cell line. These results indicate that cyclin D1 and cyclin D3 share a common mechanism of degradation and we propose that the coordinate increase of D-type cyclins observed in primary breast cancers reflects a defect in their proteolysis.  (+info)

Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. (3/749)

The von Hippel-Lindau (VHL) tumor suppressor gene is mutated in most human kidney cancers. The VHL protein is part of a complex that includes Elongin B, Elongin C, and Cullin-2, proteins associated with transcriptional elongation and ubiquitination. Here it is shown that the endogenous VHL complex in rat liver also includes Rbx1, an evolutionarily conserved protein that contains a RING-H2 fingerlike motif and that interacts with Cullins. The yeast homolog of Rbx1 is a subunit and potent activator of the Cdc53-containing SCFCdc4 ubiquitin ligase required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1 to S cell cycle transition. These findings provide a further link between VHL and the cellular ubiquitination machinery.  (+info)

Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. (4/749)

Control of cyclin levels is critical for proper cell cycle regulation. In yeast, the stability of the G1 cyclin Cln1 is controlled by phosphorylation-dependent ubiquitination. Here it is shown that this reaction can be reconstituted in vitro with an SCF E3 ubiquitin ligase complex. Phosphorylated Cln1 was ubiquitinated by SCF (Skp1-Cdc53-F-box protein) complexes containing the F-box protein Grr1, Rbx1, and the E2 Cdc34. Rbx1 promotes association of Cdc34 with Cdc53 and stimulates Cdc34 auto-ubiquitination in the context of Cdc53 or SCF complexes. Rbx1, which is also a component of the von Hippel-Lindau tumor suppressor complex, may define a previously unrecognized class of E3-associated proteins.  (+info)

Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha. (5/749)

Activation of the transcription factor NF-kappa B in response to proinflammatory stimuli requires the phosphorylation-triggered and ubiquitin-dependent degradation of the NF-kappa B inhibitor, I kappa B alpha. Here, we show the in vitro reconstitution of the phosphorylation-dependent ubiquitination of I kappa B alpha with purified components. ROC1, a novel SCF-associated protein, is recruited by cullin 1 to form a quatemary SCFHOS-ROC1 holenzyme (with Skp1 and the beta-TRCP homolog HOS). SCFHOS-ROC1 binds IKK beta-phosphorylated I kappa B alpha and catalyzes its ubiquitination in the presence of ubiquitin, E1, and Cdc34. ROC1 plays a unique role in the ubiquitination reaction by heterodimerizing with cullin 1 to catalyze ubiquitin polymerization.  (+info)

ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. (6/749)

We have identified two highly conserved RING finger proteins, ROC1 and ROC2, that are homologous to APC11, a subunit of the anaphase-promoting complex. ROC1 and ROC2 commonly interact with all cullins while APC11 specifically interacts with APC2, a cullin-related APC subunit. YeastROC1 encodes an essential gene whose reduced expression resulted in multiple, elongated buds and accumulation of Sic1p and Cln2p. ROC1 and APC11 immunocomplexes can catalyze isopeptide ligations to form polyubiquitin chains in an E1- and E2-dependent manner. ROC1 mutations completely abolished their ligase activity without noticeable changes in associated proteins. Ubiquitination of phosphorylated I kappa B alpha can be catalyzed by the ROC1 immunocomplex in vitro. Hence, combinations of ROC/APC11 and cullin proteins proteins potentially constitute a wide variety of ubiquitin ligases.  (+info)

Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function. (7/749)

The von Hippel-Lindau tumor suppressor protein pVHL assembles with cullin-2 (hCUL-2) and elongin B/C forming a protein complex, CBCVHL, that resembles SKP1-CDC53-F-box protein ubiquitin ligases. Here, we show that hCUL-2 is modified by the conserved ubiquitin-like protein NEDD8 and that NEDD8-hCUL-2 conjugates are part of CBCVHL complexes in vivo. Remarkably, the formation of these conjugates is stimulated by the pVHL tumor suppressor. A tumorigenic pVHL variant, however, is essentially deficient in this activity. Thus, ligation of NEDD8 to hCUL-2 is linked to pVHL activity and may be important for pVHL tumor suppressor function.  (+info)

Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. (8/749)

SCFCdc4 (Skp1, Cdc53/cullin, F-box protein) defines a family of modular ubiquitin ligases (E3s) that regulate diverse processes including cell cycle, immune response, and development. Mass spectrometric analysis of proteins copurifying with Cdc53 identified the RING-H2 finger protein Hrt1 as a subunit of SCF. Hrt1 shows striking similarity to the Apc11 subunit of anaphase-promoting complex. Conditional inactivation of hrt1(ts) results in stabilization of the SCFCdc4 substrates Sic1 and Cln2 and cell cycle arrest at G1/S. Hrt1 assembles into recombinant SCF complexes and individually binds Cdc4, Cdc53 and Cdc34, but not Skp1. Hrt1 stimulates the E3 activity of recombinant SCF potently and enables the reconstitution of Cln2 ubiquitination by recombinant SCFGrr1. Surprisingly, SCF and the Cdc53/Hrt1 subcomplex activate autoubiquitination of Cdc34 E2 enzyme by a mechanism that does not appear to require a reactive thiol. The highly conserved human HRT1 complements the lethality of hrt1Delta, and human HRT2 binds CUL-1. We conclude that Cdc53/Hrt1 comprise a highly conserved module that serves as the functional core of a broad variety of heteromeric ubiquitin ligases.  (+info)

*ANAPC11

2002). "APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting ... "APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex". Mol ... Ohta, T; Michel J J; Schottelius A J; Xiong Y (Apr 1999). "ROC1, a homolog of APC11, represents a family of cullin partners ... 2005). "The RING-H2-finger protein APC11 as a target of hydrogen peroxide". Free Radic. Biol. Med. 37 (4): 521-30. doi:10.1016/ ...

*ANAPC2

"APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex". Mol ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ... Ohta, T; Michel J J; Schottelius A J; Xiong Y (April 1999). "ROC1, a homolog of APC11, represents a family of cullin partners ... A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition ...

*UBE2C

2002). "APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting ... The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ... Chuang TH, Ulevitch RJ (2004). "Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors". Nat. Immunol. 5 (5): ...

*CUL4B

Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high ... protein is a CRL4 substrate only when directed by viral proteins §protein is a CRL4 substrate only when directed by IMiDs ... At the C-terminal end, CUL4B interacts with the RBX1/ROC1 protein via its RING domain. RBX1 is a core component of Cullin-RING ... This modification appears to induce conformational changes which promotes flexibility in the RING domain of cullin proteins and ...

*CUL4A

Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase ... protein is a CRL4A substrate only when directed by viral proteins §protein is a CRL4A substrate only when directed by IMiDs ... At the C-terminal end, CUL4A interacts with the RBX1/ROC1 protein via its RING domain. RBX1 is a core component of Cullin-RING ... Shiyanov P, Nag A, Raychaudhuri P (Dec 1999). "Cullin 4A associates with the UV-damaged DNA-binding protein DDB". The Journal ...

*CUL1

Cullin 1, also known as CUL1, is a human protein and gene from cullin family. This protein plays an important role in protein ... Morimoto M, Nishida T, Honda R, Yasuda H (2000). "Modification of cullin-1 by ubiquitin-like protein Nedd8 enhances the ... 1998). "Characterization of the cullin and F-box protein partner Skp1". FEBS Lett. 438 (3): 183-9. doi:10.1016/S0014-5793(98) ... 2000). "Covalent modification of all members of human cullin family proteins by NEDD8". Oncogene. 18 (48): 6829-34. doi:10.1038 ...

*3-M syndrome

The Cullin 7 gene contains instructions for making the protein Cullin-7. Cullin-7 acts as scaffold protein in the E3 ubiquitin ... Mutations in the CUL7 gene blocks the ability of the cullin-7 protein to bring together the components of this E3 ubiquitin ... Disruption of the protein degradation process plays a role in the pathogensis of prenatal growth retardation in humans, a key ... However, the implications of 3M syndrome suggest that both these genes encode for proteins that play a role in the CUL7 ...

*Neddylation

Because NEDD8 conjugation to cullin proteins plays an important role in the regulation of the cell cycle, an upregulation in ... Neddylation is the process by which the ubiquitin-like protein NEDD8 is conjugated to its target proteins. This process is ... Second, it can cause the target protein to become incompatible with other proteins that it usually binds with. For example, ... Herrmann J, Lerman LO, Lerman A. Ubiquitin and ubiquitin-like proteins in protein regulation. Circ Res. 2007;100(9):1276-91. ...

*NEDD8

Pan ZQ, Kentsis A, Dias DC, Yamoah K, Wu K (March 2004). "Nedd8 on cullin: building an expressway to protein destruction". ... Liakopoulos D, Büsgen T, Brychzy A, Jentsch S, Pause A (May 1999). "Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 ... Morimoto M, Nishida T, Honda R, Yasuda H (April 2000). "Modification of cullin-1 by ubiquitin-like protein Nedd8 enhances the ... NEDD8 is a protein that in humans is encoded by the NEDD8 gene. (In Saccharomyces cerevisiae this protein is known as Rub1.) ...

*CUL2

Cullin-2 is a protein that in humans is encoded by the CUL2 gene. CUL2 has been shown to interact with: CAND1, DCUN1D1, RBX1, ... "Entrez Gene: CUL2 cullin 2". Menon S, Tsuge T, Dohmae N, Takio K, Wei N. "Association of SAP130/SF3b-3 with Cullin-RING ... structural resemblance of the pVHL/elongin BC/hCUL-2 complex with the ubiquitin ligase complex SKP1/cullin/F-box protein". Proc ... "Covalent modification of all members of human cullin family proteins by NEDD8". Oncogene. 18 (48): 6829-34. doi:10.1038/sj.onc. ...

*CUL3

Cullin-3 is a protein that in humans is encoded by the CUL3 gene. CUL3 has been shown to interact with: CAND1, Cyclin E1, ... "Covalent modification of all members of human cullin family proteins by NEDD8". Oncogene. 18 (48): 6829-34. doi:10.1038/sj.onc. ... "BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase". Molecular and ... "Entrez Gene: CUL3 cullin 3". Min KW, Hwang JW, Lee JS, Park Y, Tamura TA, Yoon JB (May 2003). "TIP120A associates with cullins ...

*APPBP1

"Covalent modification of all members of human cullin family proteins by NEDD8". Oncogene. 18 (48): 6829-34. doi:10.1038/sj.onc. ... The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface ... APPBP1 (Amyloid Precursor Protein-Binding Protein 1) binds to the Amyloid Precursor Protein (APP) carboxy terminal domain. ... In addition, the encoded protein can form a heterodimer with UBE1C and bind and activate NEDD8, a ubiquitin-like protein. This ...

*CUL5

Cullin-5 is a protein that in humans is encoded by the CUL5 gene. The mammalian gene product was originally discovered by ... Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5. Studies ... Feng L, Allen NS, Simo S, Cooper JA (November 2007). "Cullin 5 regulates Dab1 protein levels and neuron positioning during ... 2000). "Covalent modification of all members of human cullin family proteins by NEDD8". Oncogene. 18 (48): 6829-34. doi:10.1038 ...

*Cullin

The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin ... Cullin family[permanent dead link] - Sanger Institute website. Cullin Proteins at the US National Library of Medicine Medical ... The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology ... Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) play an essential role in targeting proteins for ubiquitin-mediated ...

*SKP2

The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), ... Ng RW, Arooz T, Yam CH, Chan IW, Lau AW, Poon RY (November 1998). "Characterization of the cullin and F-box protein partner ... and Fbxos containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by ... Yam CH, Ng RW, Siu WY, Lau AW, Poon RY (January 1999). "Regulation of cyclin A-Cdk2 by SCF component Skp1 and F-box protein ...

*SKP1A

Ng RW, Arooz T, Yam CH, Chan IW, Lau AW, Poon RY (1998). "Characterization of the cullin and F-box protein partner Skp1". FEBS ... This gene encodes a protein that is a member of the SCF ubiquitin ligase protein complex. It binds to F-box proteins (proteins ... Ng RW, Arooz T, Yam CH, Chan IW, Lau AW, Poon RY (November 1998). "Characterization of the cullin and F-box protein partner ... The encoded protein also collaborates with a network of proteins to control beta-catenin levels and affects the activity level ...

*List of MeSH codes (D08)

... skp cullin f-box protein ligases MeSH D08.811.464.938.750.750.500 --- cullin proteins MeSH D08.811.464.938.750.875 --- von ... gtp-binding protein alpha subunit, gi2 MeSH D08.811.277.040.330.300.200.100.300 --- gtp-binding protein alpha subunits, gq-g11 ... proto-oncogene proteins c-bcr MeSH D08.811.913.696.620.682.700.776 --- proto-oncogene proteins c-pim-1 MeSH D08.811.913.696. ... proto-oncogene proteins c-kit MeSH D08.811.913.696.620.682.725.400.075 --- proto-oncogene proteins c-met MeSH D08.811.913.696. ...

*Reelin

Feng L, Allen NS, Simo S, Cooper JA (Nov 2007). "Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical ... D'Arcangelo G, Miao GG, Chen SC, Soares HD, Morgan JI, Curran T (Apr 1995). "A protein related to extracellular matrix proteins ... "A cdc2-related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau protein kinase II, a proline-directed protein ... "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". The ...

*DAB1

Feng L, Allen NS, Simo S, Cooper JA (2007). "Cullin 5 regulates Dab1 protein levels and neuron positioning during cortical ... UMich Orientation of Proteins in Membranes protein/pdbid-1nu2 DAB1 protein, human at the US National Library of Medicine ... 2009). "Activated protein C ligation of ApoER2 (LRP8) causes Dab1-dependent signaling in U937 cells". Proc. Natl. Acad. Sci. U. ... Such an increase in the expression of a protein that virtually functions as a receptor is expected to occur when the specific ...

*Gibberellin

The SCF complex is composed of SKP1, CULLIN, and F-BOX proteins. F-box proteins catalyze the formation of polyubiquitin on ... Trimeric G proteins are involved in GA signaling, which supports the previous theory for plasma membrane GA receptors. Four ... The rice GID1 gene encodes an unknown protein that only has a high affinity for bioactive GAs. In yeast, GID1 binds SLR1, GA ... Arabidopsis has three GID1 homologs that bind GA and interact with DELLAs: AtGID1a, b, and c. DELLA proteins, such as GAI, act ...

*COP9 signalosome

It catalyses the hydrolysis of NEDD8 protein from the cullin subunit of Cullin-RING ubiquitin ligases (CRL). Therefore, it is ... Fang, L.; Kaake, R. M.; Patel, V. R.; Yang, Y.; Baldi, P.; Huang, L. (2012). "Mapping the Protein Interaction Network of the ... COP9 (Constitutive photomorphogenesis 9) signalosome (CSN) is a protein complex with isopeptidase activity. ... responsible for CRL deneddylation - at the same time, it is able to bind denedyllated cullin-RING complex and retain them in ...

*PARC (gene)

Cullin-9 is a protein that in humans is encoded by the CUL9 gene. PARC (gene) has been shown to interact with P53. GRCh38: ... Nakayama M, Kikuno R, Ohara O (2003). "Protein-Protein Interactions Between Large Proteins: Two-Hybrid Screening Using a ... 2007). "The conserved CPH domains of Cul7 and PARC are protein-protein interaction modules that bind the tetramerization domain ... X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 5 (3): 169-76 ...

*Proteolysis targeting chimera

... chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation". Proceedings of ... one capable of engaging an E3 ubiquitin ligase and the other to a target protein meant for degradation by the cellular protein ... Recruitment of the target protein to the specific E3 ligase results in its tagging for destruction (i.e., ubiquitination) and ... Zengerle M, Chan K-H, Ciulli A (2015). "Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4". ACS ...

*Raymond J. Deshaies

CSN plays a key role in regulating SCF and other CRL enzymes by removing the ubiquitin-like protein NEDD8 from their cullin ... and biochemically-validated function to be discovered for a member of the Hsp70 family of proteins. SCF and cullin-RING ... Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proc. Natl. Acad. ... to tether cellular proteins to a ubiquitin ligase, resulting in ubiquitination and degradation of the tethered protein . This ...

*CAND1

Cullin-associated NEDD8-dissociated protein 1 is a protein that in humans is encoded by the CAND1 gene. CAND1 has been shown to ... "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome ... "Entrez Gene: CAND1 cullin-associated and neddylation-dissociated 1". Min KW, Hwang JW, Lee JS, Park Y, Tamura TA, Yoon JB (May ... Menon S, Tsuge T, Dohmae N, Takio K, Wei N (2008). "Association of SAP130/SF3b-3 with Cullin-RING ubiquitin ligase complexes ...

*WNK1

The gene belongs to a group of four related protein kinases (WNK1, WNK2, WNK3, WNK4). Homologs of this protein have been found ... There are two enzymes responsible for WNK1 ubiquitination, kelch like 3 (KLHL3) and cullin 3 (CUL3). KLHL3 serves as an adaptor ... The WNK1 protein is composed of 2382 amino acids (molecular weight 230 kDa). The protein contains a kinase domain located ... WNK (lysine deficient protein kinase 1), also known as WNK1, is an enzyme that is encoded by the WNK1 gene. WNK1 is serine- ...
E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets. The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2. E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes. Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear. According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest. According to another report EIF4E2 ubiquitination leads to its subsequent degradation. Acts as the ligase involved in ISGylation of EIF4E2.
The role of cullin E3-ubiquitin ligases for muscle homeostasis is best known during muscle atrophy, as the cullin-1 substrate adaptor atrogin-1 counts among the most well-characterized muscle atrogins. We investigated, whether cullin activity was also crucial during terminal myoblast differentiation and aggregation of acetylcholine receptors for the establishment of neuromuscular junctions in vitro.. The activity of cullin E3-ligases is modulated through posttranslational modification with the small ubiquitin-like modifier nedd8. Using either the Nae1 inhibitor MLN4924 (Pevonedistat) or siRNA against nedd8 in early or late stages of differentiation on C2C12 myoblasts, and primary satellite cells from mouse and human, we show that cullin E3-ligase activity is necessary for each step of the muscle cell differentiation program in vitro. We further investigate known transcriptional repressors for terminal muscle differentiation ZBTB38, Bhlhe41 and Id1. Due to their identified roles for terminal ...
Proteins of the BTB-kelch family are known to be involved in multiple biological processes such as migration, cytoskeleton arrangement, regulation of cell morphology, protein ubiquitination and gene expression. KBTBD8 is a new member of this family. The gene was found in a comparative transcriptome analysis of pluripotent stem cells and was therefore suggested to play a role in the regulation of pluripotency. Comparative analysis of the gene and protein sequences revealed a high conservation throughout evolution especially in the characteristic domains of BTB, BACK and kelch. We identified the Golgi apparatus as the subcellular localization of the KBTBD8 protein in non-dividing cells and could show that KBTBD8 co-localizes with α-tubulin on the spindle apparatus of mitotic cells suggesting a role in cell proliferation. In conclusion, KBTBD8 is a new member of the BTB-kelch superfamily that is located in the Golgi apparatus and translocates to the spindle apparatus during mitosis.
Cul1 and Cul3 mouse knockout experiments have revealed their indispensable roles in cell cycle progression and early embryogenesis (Table 3). The role of CUL1 in cell cycle control is understood in considerable detail. It was the pioneering work using the budding and fission yeast systems that led to the discovery of cullins and other CRL components and their role in cell cycle control (reviewed in [19]). Work in C. elegans and Drosophila has demonstrated the requirement of CUL1 for cell cycle progression (Table 3). Mechanistically, it is believed that the CUL1-based SCF regulates the mammalian cell cycle, at least in part, by using the Skp2 F-box protein, which directs the ubiquitin-dependent degradation of p27 and p21 (inhibitors of cyclin-dependent kinases), thereby activating cyclin-dependent kinases [20]. SCF malfunction has been linked to malignancy, as mutations in the Fbw7 F-box protein are frequently found in a variety of human cancers [21].. Studies with Cul4 deletion in C. elegans ...
Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes ...
Cullin-RING E3 ligases (CRLs) are the largest known family of ubiquitin ligases. The activity of some CRLs is inhibited by an eight-subunit complex known as the COP9 signalosome, which can act on the cullin subunit of CRLs and thereby influence the ubiquitylation of CRL substrates. On p. 1035, Lionel Pintard and colleagues use mass spectrometry to identify the subset of CRLs that might be regulated by the COP9 signalosome. By determining the adaptor proteins with which six of the COP9-signalosome subunits interact, the authors identify 15 CRLs that associate with the COP9 signalosome. Interestingly, most of these CRLs have a role in DNA metabolism; the authors propose that their coordinated regulation might ensure rapid CRL-mediated responses to specific physiological cues. The authors mass spectrometry analysis also reveals that Dda1, a small protein that is thought to associate with CRL4 complexes, positively regulates their ubiquitin-ligase activity. Interestingly, the expression of Dda1 and ...
In eukaryotes, the conjugation of the ubiquitinlikeprotein NEDD8 onto protein targets is an important post-translational modification. The best understood neddylation targets are the cullins, scaffold subunits of E3 ubiquitin ligases, where neddylation as well as deneddylation, facilitated by the protease activity of the CSN (COP9 signalosome), are required to control ubiquitin ligase assembly, function and ultimately substrate degradation. Little is known about the role of other deneddylating enzymes besides CSN and the role of neddylation and deneddylation of their substrates. We previously characterized Arabidopsis thaliana mutants with defects in the conserved NEDD8-specific protease DEN1 (DENEDDYLASE1). These mutants display only subtle growth phenotypes despite the strong accumulation of a broad range of neddylated proteins. Specifically, we identified AXR1 (AUXIN RESISTANT1), a subunit of the heterodimeric NAE (E1 NEDD8 ACTIVATING ENZYME), as highly neddylated in den1 mutants. Here, we ...
A second member of the E3 ubiquitin ligases, Fbxo7, is also mutated in early-onset Parkisonism [91-97]. In contrast with Parkin, which functions as a single-polypeptide E3 ligase, Fbxo7 is a component of a multisubunit E3 ligase of the Cullin-RING ligase family (CRL). CRLs are a large class of multisubunit E3 ubiquitin ligases that feature a scaffolding protein, termed a cullin, and associate with a RING-box protein (reviewed in refs [98,99]). The archetypal CRL is the SCF-type ligase family, which comprises Cullin1, Skp1, the RING protein Rbx1, and an F-box. Skp1 associates with substrate adaptor proteins that contain F-boxes (Skp1-Cullin1-Fbox), which recruits substrates to the CRL for ubiquitylation.. Until recently, Fbxo7 had only four identified substrates. The first of these is HURP (hepatoma up-regulated protein) [100]. HURP is found at high levels in hepatocellular carcinomas and is required during mitotic spindle assembly for correct alignment of chromosomes [101]. As such, it is ...
Several experimental points support the proposal that p45SKP2 is a component of a potential human SCF‐type E3 ligase. First, two yeast F‐box proteins, CDC4 and GRR1, were shown to complex independently with CDC53 and SKP1 and function as specific SIC1 and CLN receptors, respectively (Skowyra et al., 1997). In fact, purified CDC4-CDC53-SKP1 complexes mixed together with CDC34 and an E1 were found to be necessary and sufficient for the multi‐ubiquitination of SIC1 in vitro. We found that p45SKP2 also interacts with a member of the cullin family, CUL‐1, in vivo. Association was established by direct co‐immunoprecipitation in vitro and in vivo (Figures 2 and 3). In addition, p45SKP2 was capable of relocalizing CUL‐1 to the nucleus when both proteins were co‐synthesized (Figure 2F). Although the exact function(s) of cullins remain to be determined, the yeast homolog of CUL‐1, CDC53, has been clearly implicated in the degradation of critical cell cycle regulatory proteins. Genetic ...
Protein neddylation is essential for the viability of most organisms and is widely involved in the regulation of immunity, DNA damage and repair, cell signaling and cell cycle. Unlike RING-type neddylation ligases, HECT-type neddylation ligase remains less defined. Here, we show that Itch is a novel HECT-type neddylation E3 ligase and we identify JunB as a substrate of Nedd8 modification by Itch. JunB neddylation attenuates its transcriptional activity. In addition, JunB neddylation mediated by Itch promotes its ubiquitination-dependent degradation. Therefore, these findings define a new HECT-type neddylation ligase and its neddylation substrate.
The multisubunit cullin RING E3 ubiquitin ligases (CRLs) target post-translationally modified substrates for ubiquitination and proteasomal degradation. The suppressors of cytokine signaling (SOCS) proteins play important roles in inflammatory processes, diabetes, and cancer and therefore represent attractive targets for therapeutic intervention. The SOCS proteins, among their other functions, serve as substrate receptors of CRL5 complexes. A member of the CRL family, SOCS2-EloBC-Cul5-Rbx2 (CRL5SOCS2), binds phosphorylated growth hormone receptor as its main substrate. Here, we demonstrate that the components of CRL5SOCS2 can be specifically pulled from K562 human cell lysates using beads decorated with phosphorylated growth hormone receptor peptides. Subsequently, SOCS2-EloBC and full-length Cul5-Rbx2, recombinantly expressed in Escherichia coli and in Sf21 insect cells, respectively, were used to reconstitute neddylated and unneddylated CRL5SOCS2 complexes in vitro. Finally, diverse ...
A multitude of studies have demonstrated that the early phases of DNA replication are regulated by ubiquitylation. For instance, the E3 ubiquitin ligase complexes cullin-RING ligase-1 (CRL1) and cullin-RING ligase-4 (CRL4) prevent re-replication and the occurrence of genome instability by targeting pre-RC components for proteasomal degradation (reviewed in Truong et al.2). Cullin-RING ligases (CRLs) constitute a protein family of ,200 modular E3s and are composed of eight distinct subfamilies containing different cullins, namely CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7 and CUL9.3 Cullins work as molecular scaffolds assembling the different complex subunits, that is, a RING-finger protein (RBX1 or RBX2), which interacts with the ubiquitin-conjugating enzyme, an adaptor protein and one of many substrate-receptor subunits. The activity of CRLs is primarily controlled at the level of substrate recruitment. The direct recognition of the target protein by the substrate-receptor subunit and its ...
Accepts the ubiquitin-like protein NEDD8/RUB1 from the UBA3-ULA1 E1 complex and catalyzes its covalent attachment to other proteins. The major substrate is CDC53/Cullin.
The human UV-damaged DNA-binding protein Ddb1 associates with cullin 4 ubiquitin ligases implicated in nucleotide excision repair (NER). These complexes also contain the signalosome (CSN), but NER-relevant ubiquitination targets have not yet been identified. We report that fission yeast Ddb1, Cullin 4 (Pcu4), and CSN subunits Csn1 and Csn2 are required for degradation of the ribonucleotide reductase (RNR) inhibitor protein Spd1. Ddb1-deficient cells have >20-fold increased spontaneous mutation rate. This is partly dependent on the error-prone translesion DNA polymerases. Spd1 deletion substantially reduced the mutation rate, suggesting that insufficient RNR activity accounts for ~50% of observed mutations. Epistasis analysis indicated that Ddb1 contributed to mutation avoidance and tolerance to DNA damage in a pathway distinct from NER. Finally, we show that Ddb1/Csn1/Cullin 4-mediated Spd1 degradation becomes essential when cells differentiate into meiosis. These results suggest that Ddb1, ...
This gene is a member of the cullin family. The encoded protein forms a complex that functions as an E3 ubiquitin ligase and catalyzes the polyubiquitination of specific protein substrates in the cell. The protein interacts with a ring finger protein, and is required for the proteolysis of several regulators of DNA replication including chromatin licensing and DNA replication factor 1 and cyclin E. Multiple transcript variants encoding different isoforms have been found for this gene ...
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Emerging and preclinical drugs. Because the field of Ub biology is still burgeoning, many of the intermolecular interactions between specific Ub enzymes and their cognate substrates are either newly characterized or unknown. While a few drugs have been developed to specifically antagonize E2-conjugating enzymes, E3 ligases, and DUBs, none of these have yet entered advanced clinical trials (Table 1). The ubiquitination activity of some E3 ligases requires the activity of other proteins. In particular, the cullin-RING E3 ligases require covalent binding of the Ub-like protein NEDD8 to the cullin component of the E3 ligase for proper function. The compound MLN4924 is a potent inhibitor of NEDD8 activation, and the drug has been shown in multiple preclinical models to effectively block neoplastic cell proliferation (32). Phase I trials of this agent have been completed for non-hematologic malignancies, and other trials are underway or planned for the use of this drug in an array of hematologic ...
Family commitments were a factor when Larry Cullins resigned his position as Salina Central head volleyball coach back in 2003.Family also played a role when Cullins decided to return to the Mustangs this season.In 13 seasons between his Central head coaching stints, Cullins remained active in the sport, leading club teams, coaching at the junior high level and helping as an assistant at the high school.Cullins replaced Rose Wittman back in 2001 after Wittman spent six years with the Central
CSN is involved in regulating cullin-based E3 ligases and could potentially be altered in tumors. Although few studies documented the role of CSN5 in tumorigenesis (44, 45), the roles of COP9 subunits in tumorigenesis remain to be determined. Here, we discovered that CSN6 was amplified and overexpressed in cancers and was a positive regulator of ubiquitin ligase MDM2 to promote tumorigenesis. Our discovery of CSN6 in stabilizing MDM2 updates the paradigm with evidence that CSN has a versatile role in modulating various types of E3 ligases. The positive correlation between CSN6 and MDM2 in both cancer cell lines and primary tumors is particularly interesting, as MDM2 levels are associated with poor prognosis of many types of human cancer (26, 46). MDM2 is substantially amplified/overexpressed in greater than 40 different types of malignancies, and changes in MDM2 stability could be another possible explanation; however, little is known about this aspect. It is worth noting that in our collection ...
TY - JOUR. T1 - Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex. AU - Sato, Yoshitaka. AU - Kamura, Takumi. AU - Shirata, Noriko. AU - Murata, Takayuki. AU - Kudoh, Ayumi. AU - Iwahori, Satoko. AU - Nakayama, Sanae. AU - Isomura, Hiroki. AU - Nishiyama, Yukihiro. AU - Tsurumi, Tatsuya. PY - 2009/7/1. Y1 - 2009/7/1. N2 - p53-signaling is modulated by viruses to establish a host cellular environment advantageous for their propagation. The Epstein-Barr virus (EBV) lytic program induces phosphorylation of p53, which prevents interaction with MDM2. Here, we show that induction of EBV lytic program leads to degradation of p53 via an ubiquitin-proteasome pathway independent of MDM2. The BZLF1 protein directly functions as an adaptor component of the ECS (Elongin B/C-Cul2/5-SOCS-box protein) ubiquitin ligase complex targeting p53 for degradation. Intringuingly, C-terminal phosphorylation of p53 resulting from activated DNA damage response by viral lytic replication enhances its ...
SCF and other cullin-ring ligases (CRLs) have been implicated in numerous human developmental and disease pathways. These enzymes function in the ubiquitin prot...
Lan L, Nakajima S, Kapetanaki MG, Hsieh CL, Fagerburg M, Thickman K, Rodriguez-Collazo P,Leuba SH, Levine AS, Rapić-Otrin V. Monoubiquitinated histone H2A destabilizes photolesion-containing nucleosomes with concomitant release of UV-damaged DNA-binding protein E3 ligase. J Biol Chem. 2012 Apr 6;287(15):12036- ...
pep:known chromosome:VEGA66:X:38533274:38576196:-1 gene:OTTMUSG00000017236 transcript:OTTMUST00000041721 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Cul4b description:cullin 4B ...
The anaphase-promoting complex/cyclosome (APC/C) is a ubiquitin ligase with essential functions in mitosis, meiosis, and G1 phase of the cell cycle. APC/C recognizes substrates via coactivator proteins such as Cdh1, and bound substrates are ubiquitinated by E2 enzymes that interact with a hetero-dimer of the RING subunit Apc11 and the cullin Apc2. We have obtained three-dimensional (3D) models of human and Xenopus APC/C by angular reconstitution and random conical tilt (RCT) analyses of negatively stained cryo-electron microscopy (cryo-EM) preparations, have determined the masses of these particles by scanning transmission electron microscopy (STEM), and have mapped the locations of Cdh1 and Apc2. These proteins are located on the same side of the asymmetric APC/C, implying that this is where substrates are ubiquitinated. We have further identified a large flexible domain in APC/C that adopts a different orientation upon Cdh1 binding. Cdh1 may thus activate APC/C both by recruiting substrates ...
Inhibition of HIV-1 by A3G that escapes Vif mediated degradation. In an HIV-1 producer cell, the HIV-1 virus infectivity factor (Vif) interacts with the cotranscription factor CBF-β and a cellular ubiquitin ligase complex to become the substrate recognition subunit of an E3 ubiquitin ligase. (1) The Vif-E3 complex recruits an E2 enzyme that transfers ubiquitin molecules to A3G, thereby signaling it for degradation through the proteasome pathway. (2) A3G that escapes this fate, either fortuitously or in the presence of a Vif-defective HIV-1 strain, can enter an assembling virus particle through interactions with RNA (host 7SL RNA or HIV-1 genomic RNA) and the nucleocapsid portion of Gag. Then, A3G travels with the HIV-1 particle to a target cell where it waits for reverse transcription of the HIV-1 genomic RNA to (-)DNA to ensue. A3G, a single-stranded DNA deaminase is able to deaminate cytosine (C) to uracil (U) in (-)DNA, which causes the reverse transcriptase to introduce guanine (G) to ...
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In this study, we examined the potential mechanism responsible for COMMD1‐mediated repression of NF‐κB and its ability to accelerate the dissociation of RelA from chromatin (Burstein et al, 2005). Interestingly, others had reported that ubiquitination of RelA also accelerates its release from chromatin (Saccani et al, 2004), suggesting that ubiquitination of RelA might be responsible for the effects of COMMD1. Indeed, we present evidence that COMMD1 promotes the ubiquitination of NF‐κB subunits and our data also indicate that this effect is mediated by the interaction of COMMD1 with ECSSOCS1, a Cullin‐containing ubiquitin ligase complex previously implicated in RelA ubiquitination (Ryo et al, 2003). These events are physiologically important because COMMD1 deficiency results in de‐repression of several endogenous NF‐κB‐responsive genes and enhanced κB‐mediated cellular responses such as the production of chemokines. Finally, our studies indicated that the role of COMMD1 in ...
CUL4A encodes a core component of a cullin-based E3 ubiquitin ligase complex that regulates many critical processes such as cell cycle progression, DNA replication, DNA repair and chromatin remodeling by targeting a variety of proteins for ubiquitination and degradation. In the research described in this report we aimed to clarify whether CUL4A participates in multiple drug resistance (MDR) in breast cancer cells. We first transfected vectors carrying CUL4A and specific shCUL4A into breast cancer cells and corresponding Adr cells respectively. Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1/P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. On the other hand, silencing CUL4A in MCF7/Adr and MDA-MB-468/Adr cells led to the opposite
It has been known for some time that the human adenovirus serotype 5 (Ad5) E4orf6 and Sox18 E1B55K proteins work in concert to degrade p53 and to regulate selective export of late viral mRNAs during productive infection. H1299 human lung carcinoma cells after expression of E1B55K and E4orf6 using adenovirus vectors. Several species were detected and identified by mass spectroscopy and for one of these integrin α3 we went on in a parallel study to confirm it as a substrate of the complex (F. Dallaire et al. J. Virol. 83:5329-5338 2009 Although the system has some limitations it may still be of some general use in identifying candidate substrates of any viral cullin-based E3 ubiquitin ligase complex and we suggest a series of criteria for substrate validation. During the past decade protein degradation has become increasingly recognized SVT-40776 (Tarafenacin) as a critical mechanism by which cells regulate a number of fundamental processes (reviewed in references 37 57 and 59). Degradation ...
BPM1 belongs to the MATH-BTB family of proteins, which act as substrate-binding adaptors for the Cullin3-based E3 ubiquitin ligase. MATH-BTB proteins associate with Cullin3 via the BTB domain and with the substrate protein via the MATH domain. Few BPM1-interacting proteins with different functions are recognized, however, specific roles of BPM1, depending on its cellular localization have not been studied so far. Here, we found a novel bipartite nuclear localization signal at the C-terminus of the BPM1 protein, responsible for its nuclear and nucleolar localization and sufficient to drive the green fluorescent protein and cytoplasmic BPM4 protein into the nucleus. Co-localization analysis in live Nicotiana tabacum BY2 cells indicates a Cullin3 independent function since BPM1 localization is predominantly nucleolar and thus devoid of Cullin3. Treatment of BY2 cells with the proteasome inhibitor MG132 blocks BPM1 and Cullin3 degradation, suggesting turnover of both proteins through the ...
Following a map-based approach, we cloned HVE and found it to encode the Arabidopsis ortholog of mammalian CAND1. The important role of the HVE/CAND1 gene in vascular development has remained unnoticed so far, even though its cloning and the characterization of several mutant alleles have been reported by three research groups (Cheng et al., 2004; Chuang et al., 2004; Feng et al., 2004). Human CAND1 regulates the ubiquitination of target proteins by binding to unneddylated CULLIN1 (CUL1). CUL1, SKP1 and F-box proteins form SCF complexes that ligate ubiquitin moieties to proteins that will be degraded by the 26S proteasome. It has been proposed that the binding of CAND1 to unneddylated CUL1 hinders the interaction of SKP1 with CUL1 preventing the assembly of the SCF complex. After neddylation of CUL1, CAND1 is released and the SFC complex is assembled (Liu et al., 2002; Zheng et al., 2002; Hwang et al., 2003; Oshikawa et al., 2003).. Ubiquitin-mediated protein degradation is essential for auxin ...
Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001-0.1 μg/ml)-challenged conditions. However, Nrf2 activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and ...
Cullin-7 is a RING-E3 ligase protein that in humans is encoded by the CUL7 gene. It is associated with 3-M syndrome. CUL7 has been shown to interact with RBX1. GRCh38: Ensembl release 89: ENSG00000044090 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000038545 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Dias DC, Dolios G, Wang R, Pan ZQ (Dec 2002). "CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex". Proc Natl Acad Sci U S A. 99 (26): 16601-6. doi:10.1073/pnas.252646399. PMC 139190 . PMID 12481031. Arai T, Kasper JS, Skaar JR, Ali SH, Takahashi C, DeCaprio JA (Aug 2003). "Targeted disruption of p185/Cul7 gene results in abnormal vascular morphogenesis". Proc Natl Acad Sci U S A. 100 (17): 9855-60. doi:10.1073/pnas.1733908100. PMC 187864 . PMID 12904573. "Entrez Gene: CUL7 cullin 7". Kim SS, Shago M, Kaustov L, et al. (2007). "CUL7 is a novel antiapoptotic oncogene". Cancer Res. 67 (20): 9616-22. ...
The first three patients enrolled will receive 0.1 mg Cand5 in the study eye, the next three patients enrolled will receive 0.33 mg Cand5 in the study eye, the following three patients enrolled will receive 1.0 mg Cand5 in the study eye, the following three patients enrolled will receive 1.5 mg Cand5 in the study eye, and the remaining three patients enrolled will receive 3.0 mg Cand5 in the study eye. The third patient enrolled at each dose level will complete their two-week visit before the next dose level group may be treated ...
Generation and validation of RhoBTB1IND. Full-length RhoBTB1 was amplified from heart cDNA from C57BL/6J mice using the primers 5′-GCATGAACTAGTATGGACTCTGACATGGACTACGAACGAC-3′ (forward) and 5′-CATGAACTAGTTCAGGCGACAGCTGGGGACGAAT-3′ (reverse), with SpeI restriction enzyme sites inserted. RhoBTB1 cDNA was digested with SpeI and then subcloned into a previously described vector carrying the CAG promoter/enhancer, the loxP-STOP-loxP sequence, and IRES-tdTomato (53, 54). The construct was sequenced to confirm RhoBTB1 insertion and determine its orientation. The function of the RhoBTB1IND construct was tested in HEK293T cell lines. HEK293T cells plated in 6-well dishes were transfected using Lipofectamine LTX (Invitrogen, Thermo Fisher Scientific) according to the manufacturers protocol with either a Myc-RhoBTB1 or RhoBTB1IND construct with or without a plasmid encoding Cre recombinase (p185-Cre). Control transfections contained the inducible construct backbone with or without p185-Cre. The ...
The adhesion scaffolding protein NEDD9 was identified as potential pro-metastatic gene in several cancers. The molecular mechanisms of NEDD9-driven metastasis are still unknown. In this study, we show that expression of NEDD9 positively correlates with the invasive stage of breast cancer. We show that NEDD9 localizes to invadopodia and endosomes. Notably, NEDD9 depleted cells have increased levels of inactive surface receptors due to increase in fast recycling of Rab4 and Rab5 positive vesicles. Mechanistically, we found that NEDD9 binds to and scaffolds the Arf6 specific GAP - ASAP3, decreasing Arf6 activity. Thus, depletion of NEDD9 leads to activation of Arf6. Inhibition of Arf6 or re-expression of NEDD9 in shNEDD9 cells was sufficient to restore recycling rates, decrease the number of Rab4 and 5 positive vesicles and the invasive properties of tumor cells. Thus, in this work, we uncover the mechanistic basis of NEDD9-driven invasion and identify a new role for NEDD9 in Arf6-dependant ...
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iar si iar. am obosit. m-am plictisit. se anunta un post lung. se anunta un post satul.sunt un copil. in fond si la urma urmei, cand tragi linie, sunt un copil. un copil maturizat, un copil ce refuza sa imbatraneasca. asta ma tine pe linia de plutire. asta ma face sa nu innebunesc cand altii cauta…
Promovat cu tam--tam si cu multe lacrimi varsate, Me Before You este Dying Young-ul generatiei X (Y, Snowflake sau cum i se mai zice prin tratate si--n eseuri - hotnews, stiri, articole, revista presei, politica, economie, sport
购买我们的Recombinant人DDB2 protein. ab91908被验证过的分析类型包括SDS-PAGE,MS. Abcam现推出12个月产品保证。。。。。。Abcam抗体、ELISA、激动剂拮抗剂、表观遗传试剂、蛋白多肽,使用效果保证,中国70%以上现…
DDB1兔单克隆抗体[EPR6088](ab124672)可与小鼠, 大鼠, 人样本反应并经WB实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
Epiteliul simplu pavimentos scuamos este alctuit din celule turtite papilar al dermului, n hipoderm, n corionul mucoaselor, n jurul organelor mobile dup hipertrofia i hiperplazia organului,in lunile la bovine si ecvine,cand splina.
SCF ubiquitin ligases regulate the ubiquitin-dependent proteolysis of a myriad of substrate proteins, including p27, Cyclin E, and IkBa. To further gain insight into SCF regulation and function, we purified SCF from mammalian cells and found the Cop9 Signalosome associated with SCF. Interestingly, deletion of the CSN in S. pombe resulted in the hypermodification of Cul1 with Nedd8 in vivo. Furthermore, we found that the CSN can promote the removal of Nedd8 from Cul1 in vitro, suggesting CSN regulates SCF through deneddylation. To investigate the basis of CSN-dependent deneddylation activity, we analyzed the CSN and the 26S proteasome for conserved sequences that could be representative of a catalytic motif. We identified the JAMM motif in Csn5 and Rpn11 of the proteasome. Mutations in JAMM eliminated CSN-dependent deneddylating activity. Moreover, mutations in JAMM reduce the restrictive temperature of several SCF temperature sensitive mutants, suggesting that CSN acts positively on SCF ...
Ubiquitin-dependent degradation of hormone receptors is emerging as a key mechanism that regulates the magnitude and duration of hormonal effects on cells and tissues. The pituitary hormone prolactin (PRL) is involved in regulating cell differentiation, proliferation, and survival. PRL engages its receptor (PRLR) to initiate various signaling cascades, including the phosphorylation and activation of Stat5. We found that PRL promotes interaction between PRLR and the F-box protein beta-TrCP2, which functions as a substrate recognition subunit of the SCF(beta-TrCP) E3 ubiquitin ligase. This interaction requires PRLR phosphorylation and the integrity of serine 349 within a conserved motif, which is similar to conserved motifs present in other substrates of SCF(beta-TrCP). The PRLR(S349A) mutant is resistant to ubiquitination and is more stable than its wild-type counterpart. Phosphorylated PRLR undergoes ubiquitination by SCF(beta-TrCP) in vitro. Knockdown of beta-TrCP expression inhibits the ubiquitination
Kelch-like protein 3 is a protein in humans that is encoded by the KLHL3 gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex. Mutations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. GRCh38: Ensembl release 89: ENSG00000146021 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000014164 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". "Entrez Gene: Kelch-like 3 (Drosophila)". Retrieved 2012-04-26. "KLHL3 mutations cause familial hyperkalemic hypertension by ...
Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively ...
DDB1 was originally identified as a large subunit of damaged DNA-binding protein (DDB), which plays a role in DNA repair. DDB1 also functions as an adaptor molecule of Cul4/DDB1 ubiquitin E3 ligase and participates in various cellular processes. ...
Complete information for KLHL1 gene (Protein Coding), Kelch Like Family Member 1, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
View mouse Klhl40 Chr9:121777607-121783818 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
am scris despre barbati (baieti). am scris despre tati si despre dezamagiri. am scris despre vise si mare. dar despre noi (femeile) cand scriem? si noi neam prostit, iar cand scriu noi ma refer in general. unde a disparut misteriozitatea, decenta, sufletul, demnitatea? unde?:) nu vreau sa ajung la vesnicul subiect postat sani pe net…
O sarbatoare este intr-adevar reusita cand suntem impreuna. De Craciun ne bucuram mai mult cand ii avem pe cei dragi aproape! ...
MARCAINE, solutie injectabila se utilizeaza atunci cand este necesara o durata mai mare, de ex. pentru tratamentul durerii postoperatorii.
De la zi la zi vad o intelegere din ce in ce mai superficiala a ideii de lux. Industriile de lux se vad fortate sa cedeze uneori presiunii sociale, includem in lux tot ce are neaparat un pret cu multe cifre. Cifrele nu reflecta intotdeauna realitatea. Sunt doar o masura data de cineva si depinde de acel cineva cum este masura. Cand saloanele de lux au inceput sa apara pe frumos bulevard Dorobanti sau in toate zonele ultracentrale din Bucuresti, […]. ...
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC). Levels of both Nedd8 activating enzyme E1 and Nedd8- conjugating enzyme E2 were higher in ccRCC tissues and RCC cancer cells than in normal. Moreover, MLN4924 treatment led to rapid inhibition of Cullin1 neddylation and notably suppressed growth and survival as well as migration in a dose-and time-dependent manner. Mechanistic studies revealed that MLN4924 induced the accumulation of a number of CRL substrates, including p21, p27 and Wee1 to trigger DNA damage and ...
Cullin-RING E3 ubiquitin ligase complexes play a central role in targeting cellular proteins for ubiquitination-dependent protein turnover through 26S proteasome. Cullin-2 is a member of the Cullin family, and it serves as a scaffold protein for Elongin B and C, Rbx1 and various substrate recognition receptors to form E3 ubiquitin ligases. First, the composition, structure and the regulation of Cullin-2 based E3 ubiquitin ligases were introduced. Then the targets, the biological functions of complexes that use VHL, Lrr-1, Fem1b, Prame, Zyg-11, BAF250, Rack1 as substrate targeting subunits were described, and their involvement in diseases was discussed. A small molecule inhibitor of Cullins as a potential anti-cancer drug was introduced. Furthermore, proteins with VHL box that might bind to Cullin-2 were described. Finally, how different viral proteins form E3 ubiquitin ligase complexes with Cullin-2 to counter host viral defense were explained. Cullin-2 based E3 ubiquitin ligases, using many different
Background: Activation of the protein phosphatase calcineurin is a fundamental signaling event promoting hypertrophic growth and pathological remodeling of the heart. The modulatory calcineurin-interacting protein 1 (MCIP1) is an endogenous feedback inhibitor of calcineurin. We have previously shown that increasing the level of MCIP1 protein protects the heart from unrestrained activation of calcineurin, suggesting that strategies to increase MCIP1 protein in the heart may be a viable therapeutic approach. To this end we have undertaken genetic and biochemical studies to decipher mechanisms that regulate degradation of MCIP1 proteins.. Methods and Results: There are two major isoforms of MCIP1 (MCIP1.1 and MCIP1.4). MCIP1.1 levels are extremely stable with a half-life of over 8 hours in cultured cardiomyocytes. In contrast, MCIP1.4 levels are very low in an unstressed heart but increase precipitously in response to stress and calcineurin activation. Unlike MCIP1.1, the MCIP1.4 protein is ...
FBXW7 (F-box and WD40 repeat domain containing 7, also known as FBW7, hCDC4), a tumour suppressor gene, is mutated in many human malignancies.1 FBXW7 encodes the substrate recognition component of a Skp, Cullin, F-box-containing (SCF)-E3 ubiquitin ligase complex and negatively regulates multiple proteins with established roles in the control of cell division and growth, including cyclin E, c-Jun, c-Myc, mTor and Notch. There are several excellent reviews of the growing knowledge of FBXW7.2-5. As it became apparent that FBXW7 regulates many oncoproteins, it was hypothesised that mutations in FBXW7 may cause tumorigenesis. FBXW7 mutations were initially identified by Spruck et al in ovarian and breast cancer cell lines.6 ,7 Since then many studies have assessed FBXW7 mutation status in a range of cancer types, including both solid tumours and haematological neoplasms. A study by Akhoondi et al8 significantly contributed to this collection, as extensive genetic screening of over 500 primary tumours ...
0032] The processing chamber 200 may also include an ion-radical shield 242 disposed above the supporting assembly 208. The ion-radical shield 242 is electrically isolated from the chamber walls 202 and the supporting assembly 208. The ion-radical shield 242 includes a substantially flat plate 246 having a plurality of through holes 248 and a plurality of supporting legs 250 supporting the flat plate 246 and positioning the flat plate 246 at a certain distance above the supporting assembly 208. The plurality of supporting legs 250 may be disposed on the electrostatic chuck 216, the substrate adaptor 234 or the baffle 256. The plurality of through holes 248 may be distributed only within an open area 252 of the flat plate 246. The open area 252 controls the amount of ions that pass from a plasma formed in an upper volume 254 of the processing volume 206 to a lower volume 244 located between the ion-radical shield 242 and the supporting assembly 208. Exemplary ion-radical shields may be found in ...
Members of the F-box protein family, such as FBXL18, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (MIM 601434), cullin (see CUL1; MIM 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004 [PubMed 15520277]).[supplied by OMIM, Mar 2008]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data because no single transcript was available for the full length of the gene. The extent of this transcript is supported by transcript alignments and orthologous data ...
Dual phosphorylation of S32 and S36 in the TrCP1-binding motif of NF-kappa-B inhibitor alpha (NFKBIA) targets the protein to the SCF ubiquitin ligase complex, which marks it for degradation ...
MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-κB and negatively regulates inflammatory responses.MKRN2 is a novel ubiquitin E3 ligase for the p65 subunit of NF-κB and negatively regulates inflammatory responses. ...
Complete information for ERCC8 gene (Protein Coding), ERCC Excision Repair 8, CSA Ubiquitin Ligase Complex Subunit, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
https://doi.org/10.18632/oncotarget.3282 Ping Chen, Tao Hu, Yupei Liang, Yanan Jiang, Yongfu Pan, Chunjie Li, Ping Zhang, Dongping Wei, Pei Li, Lak Shin Jeong, Yiwei Chu, Hui Qi, Meng Yang, Robert...
Rabbit recombinant monoclonal Cullin 3 antibody [EPR3196Y] validated for WB, IP, Flow Cyt and tested in Human, Mouse and Rat. Referenced in 3 publications and…
Practic la 21.30 s-a dat startul distractiei in Fabrica atunci cand Gabi (DJ-ul), a ridicat volumulul si a inceput nebunia. In tot acest timp invitatii au continuat sa soseasca.Pe muzica lui Gabi am ars mai multe calorii de cat la un antrenament intens. Berea curgea si ne alimenta starea de buna dispozitie o data cu scurgerea orelor. Din cand in cand in cand ne mai opream sa extragem premii. S-au oferit manusi, casti, tricouri, pompe, cani aniversare, alte accesorii si multa, multa bere. Pe rand premiile au fost inmanate de catre toti colegii nostri din BikeXpert sau de catre invitatii speciali precum campionul Razvan Juganaru, riderul Alex Stancu sau colegul de bransa Bebe. Scena a facut loc si baietilor de la Bike Trial Bucuresti care au facut un demo de trial ...
Elie Saab incanta lumea modei cu acele rochii care iti taie respiratia. De cate ori vad un fashion show Elie Saab, ma gandesc cat de mult inseamna sa cunosti femeia ca sa ii creezi o asemenea rochie care pur si simplu o transforma in zeita. Elie Saab, ca si marca de parfumuri, m-a cucerit de cand mirosit primul parfum. Stiu ca eram intr-un aeroport, le-am vazut prima data si cand le-am mirosit am zis ca unde au stat ascunse pana […]. ...
Varice Varicele sau boala varicoasa - este boala cea mai frecventa a venelor si se caracterizeaza prin dilatari segmentare pe trunchiuri venoase mai mari sau cu aspect reticulat la venele mai mici. Cand sunt situate superficial, aceste vene devin vizibile, dilatate si Generalitati Tromboza venoasa profunda este reprezentata de formarea unui cheag de sange tromb in venele profunde ale http://blogelescorpion.co/varice-ale-pelvisului-femeilor-gravide.php inferioare, pelvisului sau membrele superioare.. Trombii se tratament sanatoriu tromboflebită forma fie la nivelul venelor http://blogelescorpion.co/varice-ale-semnelor-extremiti-inferioare-1.php tratament sanatoriu tromboflebită se numeste tratament sanatoriu tromboflebită Generalitati Flebita este o afectiune caracterizata prin inflamatia unei vene care poate provoca dureri si umflaturi. Tratament sanatoriu tromboflebită cand inflamatia este cauzata de prezenta unui cheag de sange sau de continue reading, conditia poarta denumirea de ...
A peaceful rural retreat on the borders of the Hautes Pyren es and the Gers, a perfect place to de-stress and explore one of the most underpopulated areas of France. A car is essen
postat de dracu in 2008-01-12 21:28 Urla in mine nevoia de a impartasi cu iubitii mei cetitori cum ma gaseste lumea pe net. Nu de altceva, da e de ras bine. Cred ca o sa fac o categorie speciala pt treaba asta :D * cand ramai insarcinata ti se intaresc sfarcurile? Cui ii mai pasa,…
Aceasta poveste magica incepe pe o insula indepartata, unde se naste un prieten imaginar. Asteapta cuminte sa-i vina randul sa fie ales de un copil din lumea reala. Dar cand vede ca nu se intampla nimic, porneste intr-o calatorie incredibila spre orasul cuprins de agitatie. Acolo isi gaseste in sfarsit perechea perfecta si primeste - dupa atata asteptare - un nume special: Beekle.
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
T cell acute lymphoblastic leukemia (T-ALL) is a disease induced by transformation of hematopoietic stem cells/progenitors. It afflicts mainly children and adol...
Looking for online definition of CAND1 or what CAND1 stands for? CAND1 is listed in the Worlds largest and most authoritative dictionary database of abbreviations and acronyms
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit(1,2). However, many cancer patients fail to respond to anti-PD-1/PD-L1 treatment, and the underlying mechanism(s) is not well understood(3-5). Recent studies revealed that response to PD-1/PD-L1 blockade might correlate with PD-L1 expression levels in tumor cells(6,7). Hence, it is important to mechanistically understand the pathways controlling PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1/PD-L1 blockade in cancer patients ...
An arrayed siRNA collection targeting human Cullin, E1, E2 and HECT E3 ubiquitin ligases. siGENOME siRNA is a cost-effective choice for RNAi screening. Available as SMARTpool or 4 individual siRNA reagents.
Cand2 - mouse gene knockout kit via CRISPR, 1 kit. |dl||dt|Kit Component:|/dt||dd|- |strong|KN302496G1|/strong|, Cand2 gRNA vector 1 in |a href=http://www.origene.com/CRISPR-CAS9/Detail.
NEDD8 a member of the ubiquitin family of proteins. Approximately 60% identical to ubiquitin protein.. Activated by an E1-like complex, consisting of App-b1 and Uba3 and then linked to the E2-like enzyme, Ubc12. The major target protein modified by nedd8 is cullin-4a. Down-regulated during the development of brain. Note: This description may include information from UniProtKB ...
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Summary of KLHL13 (BKLHD2, FLJ10262, KIAA1309) expression in human tissue. Cytoplasmic and nuclear expression in several tissues.
Regleaza tranzitul intestinal Meridian Intestin Gros este un amestec de pulberi din 17 plante medicinale, cu rol de reglare a functiei intestinului gros. Meridianul Intestin Gros, atunci cand este echilibrat energetic, contribuie la mentinerea in stare optima a digestiei, dar ne ofera si capacitatea de a ne adapta la situatiile noi pe care ni le ofera ...
Three M syndrome 1 (3M1; MIM 273750) , 2 (3M2; MIM 612921) and 3 (3M3; MIM 614205) are autosomal recessive disorders characterized by pre- and postnatal growth retardation, large head circumference, and a characteristic facial appearance including a pointed triangular shaped face, frontal bossing, midface hypoplasia, a short upturned nose with anteverted nares and full lips. Additional findings include slender long bones, tall vertebral bodies, delayed bone age and prominent heels. Intracranial aneurysms have also been rarely reported. To date, mutations in the CUL7 (cullin 7), OBSL1 (obscurin-like 1) and CCDC8 (coiled-coil domain-containing protein 8) genes have been linked to 3M1, 3M2 and 3M3, respectively. There are no apparent phenotypic differences between patients with mutations in CUL7, OBSL1 or CCDC8. 3M1, gloomy face syndrome and Yakut short stature syndrome are allelic disorders. The product of CUL7 assembles an E3 ubiquitin ligase complex involved in the ubiquitin-proteasome pathway. ...
Despite inherent limitations due to amino acid sequence constraints, all the PRISM-SRM assays developed using Arg-C digestion showed a linear dynamic range of at least two orders of magnitude, with limits of quantification ranged from 0.1 to 1 fmol/μg of total protein in the cell lysate. Applying these SRM assays to analyze HEK293T cells with and without expression of the three most frequent SPOP mutations in prostate cancer (Y87N, F102C or F133V) led to confident detection of all three SPOP mutations in corresponding positive cell lines but not in the negative cell lines. Expression of the F133V mutation and wild-type SPOP was at much lower levels compared to that of F102C and Y87N mutations; however, at present, it is unknown if this also affects the biological activity of the SPOP protein.. CONCLUSIONS ...
The COP9 signalosome is a highly conserved protein complex composed of eight subunits. In this study a novel, regulatory mechanism of CSN biogenesis was identified. We used stable transfected siCSN1 cells in which the protein and the mRNA expression of CSN subuntis were downregulated. Transfection of His-CSN1 in those siCSN1 cells led to the induction of the de novo Synthesis of the whole CSN complex. In addition the expression of the transcription factors STAT1 and c-Myc was elevated. The cells were treated with IFN alpha or IFN gamma, respectively. This resulted in the induction of the CSN de novo synthesis. Moreover, the siRNA-mediated inhibition of STAT1, c-Myc, Lin28B as well as treatment with the pharmacological inhibitors AG9 or AG490 led to a reduced protein expression of the analysed CSN subunits. We found that in all experiments there was a significant change on protein level in contrast to a marginal change on the RNA level. Based on our study we hypothesized that the CSN biogenesis ...
Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 ...
Claudia D. Spies, M.D.; Vera von Dossow, M.D. Dr. med.; Verena Eggers, M.D. Dr. med.; Gesine Jetschmann, cand med.; Ratiba El-Hilali, cand med.; Julia Egert, cand med.; Marc Fischer, cand med.; Torsten Schröder, M.D. Dr. med.; Conny Höflich, M.D. Dr. med.; Pranav Sinha, M.D.; Christian Paschen, M.D. Dr. med.; Parwis Mirsalim, M.D. Dr. med.; Ralf Brunsch, M.D. Dr. med.; Jürgen Hopf, M.D.; Christian Marks, M.D. Dr. med.; Klaus-D. Wernecke, Ph.D.; Fritz Pragst, M.D.; Hannelore Ehrenreich, M.D., Ph.D.; Christian Müller, Ph.D.; Hanne Tonnesen, M.D.; Wolfgang Oelkers, M.D.; Wolfgang Rohde, M.D.; Christoph Stein, M.D.; Wolfgang J. Kox, M.D., PhD ...
Rabbit polyclonal CRLS1 antibody validated for WB and tested in Human. Referenced in 1 publication. Immunogen corresponding to synthetic peptide
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The COP9 signalosome (CSN) is a conserved protein complex, typically composed of eight subunits (designated as CSN1 to CSN8) in higher eukaryotes such as ...
Exceptand fructele de padure, gustul de la tarta asta ne-a amintit de branzoici. Ne-a placut tare, tare mult. Chiar daca initial am pus felia de limeta mai mult pentru aspect, cand am mancat-o, am turnat pe deasupra sucul. A fost foarte buna! Marturisesc ca am facut o pasiune si pentru farfuria asta. Imi place turcoazul,…. Read More ». ...
Vinul rosu este considerat de OMS aliment. Atunci cand este consumat in moderatie, ceea ce inseamna un pahar (250 ml) de vin pe zi la femei si doua pahare la barbati. cum zice o reclama de pe unele sticle de vin : a un pahar de vin pe zi t
Atunci cand a venit pe lume, pe 17 septembrie, Nadia a socat intreg mapamondul, intrand rapid in Cartea Recordurilor drept cel mai gras bebelus al tuturor timpurilor, informeaza Reuters
Syarela, pe numele adevarat Valentina Visarion Mingopol a absolvit doua facultati: Electronica, telecomunicatii si tehnologia informatiei din cadrul Facultatii Politehnica Bucuresti si Facultatea de teatru si film, urmandu-le in paralel. De asemenea, a absolvit Scoala populara de arte, sectia muzica usoara cand era mai micuta ...
题目:StatisticalInferencesonAveragePrecisionandROCCurves(基于平均准确率与ROC曲线的统计推断)主讲人:苏婉华副教授主持人:夏苏建副教授时间:2018年12月13日15:00地点:医学院大楼530报告厅主讲嘉宾简介苏婉华博士
Maintenance of muscle structure and function depends on the precise organization of contractile proteins into sarcomeres and coupling of the contractile apparatus to the sarcoplasmic reticulum (SR), which serves as the reservoir for calcium required for contraction. Several members of the Kelch superfamily of proteins, which modulate protein stability as substrate-specific adaptors for ubiquitination, have been implicated in sarcomere formation. The Kelch protein Klhl31 is expressed in a muscle-specific manner under control of the transcription factor MEF2. To explore its functions in vivo, we created a mouse model of Klhl31 loss of function using the CRISPR-Cas9 system. Mice lacking Klhl31 exhibited stunted postnatal skeletal muscle growth, centronuclear myopathy, central cores, Z-disc streaming, and SR dilation. We used proteomics to identify several candidate Klhl31 substrates, including Filamin-C (FlnC). In the Klhl31-knockout mice, FlnC protein levels were highly upregulated with no change ...
The F-box domain is a protein structural motif of about 50 amino acids that mediates protein-protein interactions. The F-box protein is one of the four components of the SCF (SKp1, Cullin, F-box protein) complex, which mediates ubiquitination of proteins targeted for degradation by the proteasome, playing an essential role in many cellular processes. Several discoveries have been made on the use of the ubiquitin-proteasome system by viruses of several families to complete their infection cycle. On the other hand, F-box proteins can be used in the defense response by the host. This review describes the role of F-box proteins and the use of the ubiquitin-proteasome system in virus-host interactions.
Protein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to proteins being degraded is performed by a reaction cascade consisting of three enzymes, named E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin ligase). Each E3 has specificity to its substrate, or proteins to be targeted by ubiquitination. Many E3s are discovered in eukaryotes and they are classified into four types: HECT type, U-box type, single RING-finger type, and multi-subunit RING-finger type. Multi-subunit RING-finger E3s are exemplified by cullin-Rbx E3s and APC/C. They consist of a RING-finger-containing subunit (RBX1 or RBX2) that functions to bind E2s, a scaffold-like cullin molecule, adaptor proteins, and a target recognizing subunit that binds substrates ...
3M syndrome is a disorder that causes short stature (dwarfism), unusual facial features, and skeletal abnormalities. The name of this condition comes from the initials of three researchers who first identified it: Miller, McKusick, and Malvaux. It is caused by mutations in the CUL7 gene and is inherited in an autosomal recessive pattern ...
In addition, many E3s have been implicated in human disease and are attractive targets for drug discovery. However, currently no small molecule modulators for this class of enzymes have reached the clinic. Each E3 enzyme targets a small number of proteins for Ub modification but the exact substrates are mostly unknown and their identification continues to be a challenge. E3 ligase enzymes are a large (> 500) and complex super- family, many of which contain binding domains to interact with ubiquitin, E2 enzymes and substrate proteins. In addition to substrate ubiquitination, many E3 ligases can also self- or auto-ubiquitinate in the presence of an E2 enzyme, a property that may be used as an auto-regulatory mechanism to control its own intracellular levels. In general, the detailed molecular mechanism, stoichiometries and linkage site selection of E3 enzymes are poorly understood. As with ubiquitin E3 ligases, similar activities are also part of the final conjugation processes for other UBL ...
The human cytidine deaminase Apobec3F (h-A3F) a protein linked to the previously recognized antiviral factor Apobec3G (h-A3G) has antiviral activity against individual immunodeficiency virus type 1 (HIV-1) thats suppressed with the viral protein Vif. E3 ubiquitin ligase. Disturbance with Cul5-E3 ligase function by depletion of Cul5 through RNA disturbance or overexpression of Cul5 mutants obstructed the power of HIV-1 Vif to suppress h-A3F. A BC-box mutant of HIV-1 Vif that didnt recruit Cul5-E3 ligase but was still in a position to connect to h-A3F didnt suppress h-A3F. Oddly enough disturbance with Cul5-E3 ligase function or overexpression of h-A3F or h-A3G also elevated the balance of HIV-1 Vif recommending that just like the substrate substances h-A3F and h-A3G the substrate receptor proteins Vif is certainly itself also governed by Cul5-E3 ligase. Our outcomes indicate that Cul5-E3 ligase is apparently a common pathway hijacked by HIV-1 Vif to beat both h-A3F and h-A3G. Developing ...
Looking for online definition of ubiquitin-like protein ISG15 in the Medical Dictionary? ubiquitin-like protein ISG15 explanation free. What is ubiquitin-like protein ISG15? Meaning of ubiquitin-like protein ISG15 medical term. What does ubiquitin-like protein ISG15 mean?
Author summary Ubiquitin and ubiquitin-like post-translational modifications are evolutionarily conserved and involved in fundamental cellular processes essential to all eukaryotes. As such, enzymatic components of these pathways present attractive targets for therapeutic intervention for both chronic and communicable diseases. Nedd8 modification of cullin ubiquitin E3 ligases is critical to the viability of eukaryotic organisms and mediates cell cycle progression and DNA damage repair. Given the complex lifecycle and unusual replication mechanisms of the malaria parasite, one would expect neddylation to be of central importance to its survival, yet little is known about this pathway in Plasmodium. Here we present our findings on how Nedd8 removal is controlled in Plasmodium falciparum and how this pathway differs to that of its human host.

Cullin Proteins - MeSH - NCBICullin Proteins - MeSH - NCBI

All MeSH CategoriesChemicals and Drugs CategoryAmino Acids, Peptides, and ProteinsProteinsCell Cycle ProteinsCullin Proteins ... EnzymesLigasesUbiquitin-Protein Ligase ComplexesUbiquitin-Protein LigasesSKP Cullin F-Box Protein LigasesCullin Proteins ... Cullin Proteins. A family of structurally related proteins that were originally discovered for their role in cell-cycle ... Cullin Protein. All MeSH CategoriesChemicals and Drugs CategoryEnzymes and Coenzymes ...
more infohttps://www.ncbi.nlm.nih.gov/mesh?Db=mesh&Cmd=DetailsSearch&Term=%22Cullin+Proteins%22%5BMeSH+Terms%5D

The cullin protein family | Genome Biology | Full TextThe cullin protein family | Genome Biology | Full Text

Cullin protein domain organization in humans. Cullin repeat 1 (CR1) anchors the cognate adaptor proteins, and the cullin ... The mammalian cullin protein family comprises eight members (CUL1 to CUL7 and PARC). In CRL, a cullin protein tethers both a ... Modularity of cullin-RING E3 ligases. Cullin proteins are molecular scaffolds that assemble multi-subunit cullin-RING E3 ... A cullin protein tethers both a substrate-targeting unit, often through an adaptor protein, and the RING finger component in a ...
more infohttps://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-4-220

Cloning and expression of HVACM, a cullin protein, from small cell lung cancer. :: Dartmouth DissertationsCloning and expression of HVACM, a cullin protein, from small cell lung cancer. :: Dartmouth Dissertations

CLONING AN D EXPRESSION OF HVACM, A CULLIN PROTEIN, FROM SMALL CELL LUNG CANCER A Thesis Subm itted to the Faculty in p artial ... CLONING AN D EXPRESSION OF HVACM, A CULLIN PROTEIN, FROM SMALL CELL LUNG CANCER A Thesis Subm itted to the Faculty in p artial ... Cloning and expression of HVACM, a cullin protein, from small cell lung cancer. ... Cloning and expression of HVACM, a cullin protein, from small cell lung cancer.. ...
more infohttp://libarchive.dartmouth.edu/cdm/compoundobject/collection/dcdis/id/313699/rec/41

CUL1 Protein  Human Recombinant | Cullin 1 Antigen | ProSpecCUL1 Protein Human Recombinant | Cullin 1 Antigen | ProSpec

Cullin1, is an essential component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase ... The CUL1 protein solution (1mg/1ml) is formulated in 20mM Tris-HCl buffer (pH8.0) 1mM DTT, 100mM NaCl and 10% glycerol. ... Cullin1 assists in a rigid scaffold which organizes the SKP1-F-box protein and RBX1 subunits. Cullin1 contributes to catalysis ... complexes, that facilitate the ubiquitination of proteins which take part in cell cycle progression, signal transduction and ...
more infohttps://www.prospecbio.com/CUL1_Human

CAND1 - Cullin-associated NEDD8-dissociated protein 1 - Homo sapiens (Human) - CAND1 gene & proteinCAND1 - Cullin-associated NEDD8-dissociated protein 1 - Homo sapiens (Human) - CAND1 gene & protein

Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. F5H6I6. Q86VP6. A7MBJ5. F6XT20. K7DMQ8. H9EMN0. ... Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. F5H6I6. Q86VP6. A7MBJ5. F6XT20. K7DMQ8. H9EMN0. ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. F5H6I6. A0A091D3K4. UPI000523E876. UPI000521C187 ...
more infohttp://www.uniprot.org/uniprot/F5H6I6

CUL1 - Cullin-1 - Pongo abelii (Sumatran orangutan) - CUL1 gene & proteinCUL1 - Cullin-1 - Pongo abelii (Sumatran orangutan) - CUL1 gene & protein

The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of ... SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell ... In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to ... The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and ...
more infohttps://www.uniprot.org/uniprot/Q5R4G6

A RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligasesA RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases

Prototypic CRLs, "SCFs", comprise the scaffold protein CUL1, the RING protein RBX1, the adaptor SKP1, and an F-box protein that ... A RING E3-substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases. Matthew F ... E2 and E3 enzymes covalently link ubiquitin-like proteins (UBLs) to their protein targets. The largest family of E3s comprises ... We reasoned that cullin-RBX1 complexes likely exist in conformations other than those seen previously, and in efforts to ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC3245743/?lang=en-ca

Cullin-associated NEDD8-dissociated protein 1Cullin-associated NEDD8-dissociated protein 1

The encoded protein binds to unneddylated cullin-RING box protein complexes and acts as an inhibitor of cullin neddylation and ... COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin- ... The Epstein-Barr virus protein BPLF1, is targeted to cullin-RING ubiquitin ligases (CRLs) via the interaction of the conserved ... neddylated cullin 3 (Cul3) and the BTB protein Keap1.. ... UniProt Keyword for Cullin-associated NEDD8-dissociated protein ...
more infohttps://pharos.nih.gov/idg/targets/Q86VP6

Isolated DNA encoding cullin regulators ROC1 and ROC2, isolated proteins     encoded by the same, and methods utilizing the...Isolated DNA encoding cullin regulators ROC1 and ROC2, isolated proteins encoded by the same, and methods utilizing the...

Methods of producing the ROC1 and ROC2 proteins are also disclosed, and methods of detecting the polynucleotides in samples are ... The present invention further includes methods for screening bioactive agents that are capable of binding to a ROC protein, ... the isolated proteins themselves, expression vectors containing at least a fragment of the ROC1 and ROC2 polynucleotide ... protein. Such screening methods are capable of identifying compounds that have pharmacological. Pharmaceutical formulations ...
more infohttp://www.patentgenius.com/patent/7625732.html

Respiratory Syncytial Virus NS1 Protein Degrades STAT2 by Using the Elongin-Cullin E3 Ligase | Journal of VirologyRespiratory Syncytial Virus NS1 Protein Degrades STAT2 by Using the Elongin-Cullin E3 Ligase | Journal of Virology

Protein alignments.Protein alignments between RSV NS proteins, elongin C-interacting proteins (SOCS1 to -3 and VHL), and Cul2- ... A and B) CLUSTALW protein alignments of RSV NS1 protein and elongin C-interacting proteins (VHL and SOCS1 to -3) (A) and (B) ... tumor suppressor protein (9, 12, 17). These proteins assemble a multisubunit complex consisting of elongin BC, a cullin (Cul) ... including nucleocapsid proteins (N, P, and L), surface proteins (F and G), and a matrix protein (M). In addition, the genome ...
more infohttps://jvi.asm.org/content/81/7/3428?ijkey=5dccc75a68b18edc4dee73068e80fc4c6354414b&keytype2=tf_ipsecsha

Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases<...Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases<...

Cullin family proteins bind with the RING-finger protein Roc1 to recruit the ubiquitin-conjugating enzyme (E2) to the ubiquitin ... Cullin family proteins bind with the RING-finger protein Roc1 to recruit the ubiquitin-conjugating enzyme (E2) to the ubiquitin ... Cullin family proteins bind with the RING-finger protein Roc1 to recruit the ubiquitin-conjugating enzyme (E2) to the ubiquitin ... Cullin family proteins bind with the RING-finger protein Roc1 to recruit the ubiquitin-conjugating enzyme (E2) to the ubiquitin ...
more infohttps://nebraska.pure.elsevier.com/en/publications/targeting-of-protein-ubiquitination-by-btb-cullin-3-roc1-ubiquiti

Regulation of NCX1 by palmitoylation.Regulation of NCX1 by palmitoylation.

... to intracellular cysteine residues of proteins via a thioeste... ... Cullin Proteins. A family of structurally related proteins that ... S-Acylation of Proteins.. Palmitoylation or S-acylation is the posttranslational attachment of fatty acids to cysteine residues ... Synaptosomal-associated protein of 23 kDa (SNAP-23) plays an important role during regulated exocytosis of various inflammatory ... The cysteine-rich domain of synaptosomal-associated protein of 23 kDa (SNAP-23) regulates its membrane association and ...
more infohttps://www.bioportfolio.com/resources/pmarticle/2588302/Regulation-of-NCX1-by-palmitoylation.html

CUL4A cullin 4A [Homo sapiens (human)] - Gene - NCBICUL4A cullin 4A [Homo sapiens (human)] - Gene - NCBI

Cullin_Nedd8; Cullin protein neddylation domain. pfam00888. Location:65 → 657. Cullin; Cullin family. ... Cullin_Nedd8; Cullin protein neddylation domain. pfam00888. Location:2 → 557. Cullin; Cullin family. ... Cullin_Nedd8; Cullin protein neddylation domain. pfam00888. Location:2 → 565. Cullin; Cullin family. ... Cullin_Nedd8; Cullin protein neddylation domain. pfam00888. Location:2 → 557. Cullin; Cullin family. ...
more infohttps://www.ncbi.nlm.nih.gov/gene/8451

Abstract 1480: A Cullin 4a E3 Ligase Complex Mediates Rapid Degradation of the Calcineurin Regulatory Protein MCIP1.4 In...Abstract 1480: A Cullin 4a E3 Ligase Complex Mediates Rapid Degradation of the Calcineurin Regulatory Protein MCIP1.4 In...

Abstract 1480: A Cullin 4a E3 Ligase Complex Mediates Rapid Degradation of the Calcineurin Regulatory Protein MCIP1.4 In ... Abstract 1480: A Cullin 4a E3 Ligase Complex Mediates Rapid Degradation of the Calcineurin Regulatory Protein MCIP1.4 In ... Abstract 1480: A Cullin 4a E3 Ligase Complex Mediates Rapid Degradation of the Calcineurin Regulatory Protein MCIP1.4 In ... Abstract 1480: A Cullin 4a E3 Ligase Complex Mediates Rapid Degradation of the Calcineurin Regulatory Protein MCIP1.4 In ...
more infohttp://circ.ahajournals.org/content/116/Suppl_16/II_305.2

Frontiers | Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease | OncologyFrontiers | Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease | Oncology

Aberrant expression of the cullin 4A (CUL4A) gene is found in many tumor types, while mutations of the cullin 4B (CUL4B) gene ... substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. Aberrant ... expression of the cullin 4A (CUL4A) gene is found in many tumor types, while mutations of the cullin 4B (CUL4B) gene are ... substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. ...
more infohttps://www.frontiersin.org/articles/10.3389/fonc.2012.00021/full

The Draft Genome and Transcriptome of Panagrellus redivivus Are Shaped by the Harsh Demands of a Free-Living Lifestyle |...The Draft Genome and Transcriptome of Panagrellus redivivus Are Shaped by the Harsh Demands of a Free-Living Lifestyle |...

Distance-based protein tree of cullin homology domain-containing proteins among nematodes. All five major nematode cullin ... P. redivivus has six CUL-1-like proteins, two APC-2-like proteins, and four other cullin homology domain-containing proteins ... The sequenced genome shows expansions of cullin proteins, GPCRs, BTB-domain-containing proteins, and immune effectors. These ... CUL-1 CRLs use F-box proteins for substrate specificity, while those with a CUL-3 cullin scaffold use BTB proteins for ...
more infohttp://www.genetics.org/content/193/4/1279.long

Regulation of the Nrf2-Keap1 Antioxidant Response by the Ubiquitin Proteasome System: An Insight into Cullin-Ring Ubiquitin...Regulation of the Nrf2-Keap1 Antioxidant Response by the Ubiquitin Proteasome System: An Insight into Cullin-Ring Ubiquitin...

CAND1 does not bind all Cullin proteins and does not bind the same Cullin proteins in all cell types, indicating the role of ... Cul5 uses elongins B and C as linker proteins to form a complex between a SOCS box-containing protein and the Cullin protein ( ... Cullin 3 (Cul3) serves as a scaffolding protein that is bound to both Rbx1 and Keap1, which is the substrate adaptor protein ... There are numerous Cullin-ring ligases (CRLs) composed of different Cullin and substrate adaptor proteins (Fig. 2). Their ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC2966484/

Plus itPlus it

The role of cullin proteins in gastric cancer. Tumour Biol 2016;37:29-37. ... Cullin2 (Cul2) is a core component of multiple ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, ... which mediate the ubiquitination of target proteins. Cul2 was predicted to be a tumor-suppressor protein that degrades ... Repressor activator protein 1-promoted colorectal cell migration is associated with the regulation of Vimentin. Tumour Biol ...
more infohttp://cancerres.aacrjournals.org/content/78/15/4150

Regulation of the MEI-1/MEI-2 Microtubule-Severing Katanin Complex in Early Caenorhabditis elegans Development | G3: Genes |...Regulation of the MEI-1/MEI-2 Microtubule-Severing Katanin Complex in Early Caenorhabditis elegans Development | G3: Genes |...

2005 The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae. Nature 435: 1257- ... K63 ubiquitin modifies protein location, protein-protein interactions, and/or trafficking, although cases of target degradation ... 2003 Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases. Nat. Cell Biol. 5: 1001-1007. ... 2003 Exclusion of germ plasm proteins from somatic lineages by cullin-dependent degradation. Nature 424: 685-689. ...
more infohttps://www.g3journal.org/content/6/10/3257

VprBP Targets Merlin to the Roc1-Cul4A-DDB1 E3 Ligase Complex for Degradation - PubMedVprBP Targets Merlin to the Roc1-Cul4A-DDB1 E3 Ligase Complex for Degradation - PubMed

Cullin Proteins / metabolism *. Actions. * Search in PubMed * Search in MeSH * Add to Search ... Damaged DNA binding protein 1, DDB1, bridges an estimated 90 or more WD40 repeats (DDB1-binding WD40, or DWD proteins) to the ... The NF2-encoded protein Merlin is closely related to the Ezrin-Radixin-Moesin family of membrane/cytoskeleton linker proteins, ... Human Immunodeficiency Virus Type 1 Vpr-binding Protein VprBP, a WD40 Protein Associated With the DDB1-CUL4 E3 Ubiquitin Ligase ...
more infohttps://pubmed.ncbi.nlm.nih.gov/18332868/

Zhou, Z.<...Zhou, Z.<...

Cullin 4-DCAF Proteins in Tumorigenesis. Zhou, Z., Song, X., Wavelet, C. M. & Wan, Y., Jan 1 2020, Advances in Experimental ...
more infohttps://www.scholars.northwestern.edu/en/persons/zhuan-zhou

Fbxw8 is localized at the Golgi apparatus in neurons.(A | Open-iFbxw8 is localized at the Golgi apparatus in neurons.(A | Open-i

Cullin Proteins/metabolism*. *Cytoskeletal Proteins/metabolism*. *Dendrites/enzymology*/physiology. *F-Box Proteins/metabolism* ... Mentions: Among F-box proteins, Fbxw8 uniquely assembles with the scaffold protein Cul7 [21],[22], and unlike Cul1, which may ... Mentions: Among F-box proteins, Fbxw8 uniquely assembles with the scaffold protein Cul7 [21],[22], and unlike Cul1, which may ... Finally, we identify the Golgi protein Grasp65 as a novel and physiologically relevant substrate of Cul7(Fbxw8) in the control ...
more infohttps://openi.nlm.nih.gov/detailedresult.php?img=PMC3091842_pbio.1001060.g001&req=4

CUL3 - PrimePCR Assay and Template | Life Science | Bio-RadCUL3 - PrimePCR Assay and Template | Life Science | Bio-Rad

This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination ... cullin 3 Assay Type: SYBR® Green Assay Design: Intron-spanning Application: Gene Expression Unique Assay ID: qHsaCID0014787 ... cullin 3 Assay Type: Probe Assay Design: exonic Application: Gene Expression Unique Assay ID: qHsaCEP0049326 FAM HEX TEX 615 ... cullin 3 Assay Type: SYBR® Green Assay Design: exonic Application: Gene Expression Unique Assay ID: qHsaCED0042063 Info: Same ...
more infohttp://www.bio-rad.com/en-us/prime-pcr-assays/gene/cul3-human

Plus itPlus it

... as a novel Chk1-interacting protein. DDB1 is part of an E3 ligase complex that includes the cullin proteins Cul4A and Cul4B. We ... DDB1 is part of an E3 ligase complex that includes the cullin proteins Cul4A and Cul4B ( 28, 32). Interestingly, Cul4A has been ... Cul4A was immunoprecipitated from 1 mg of total cell protein using 2 μL of anti-Cul4A antibody and 50 μL of protein A-agarose ... Here, we show that damaged DNA-binding protein 1 (DDB1), a triple β propeller adapter protein, targets the Cul4 E3 ubiquitin ...
more infohttp://cancerres.aacrjournals.org/content/69/6/2630

Frontiers | CRL Ubiquitin Ligases and DNA Damage Response | OncologyFrontiers | CRL Ubiquitin Ligases and DNA Damage Response | Oncology

Cullin/RING ubiquitin ligases (CRL) comprise the largest subfamily of ubiquitin ligases and are involved in various biological ... Cullin/RING ubiquitin ligases (CRL) comprise the largest subfamily of ubiquitin ligases and are involved in various biological ... Skp1 is the linker protein that mediates association of Cdc4 with the scaffold cullin protein, Cdc53. Rbx1 (also called ROC1 or ... Sarikas, A., Hartmann, T., and Pan, Z. Q. (2011). The cullin protein family. Genome Biol. 12, 220. ...
more infohttps://www.frontiersin.org/articles/10.3389/fonc.2012.00029/full
  • OBSL1 forms a physical complex with the scaffold protein Cul7 and thereby localizes Cul7 at the Golgi apparatus. (nih.gov)
  • Table 1 presents a list of the cullin family genes from a range of representative species with respect to their gene organization and expression. (biomedcentral.com)
  • Recombinant RSV lacking the NS1 and NS2 genes induced high levels of IFN-α and -β in human pulmonary epithelial cells (A549) as well as in macrophages derived from primary human peripheral blood monocytes, highlighting the importance of these proteins in suppressing an antiviral response ( 29 ). (asm.org)
  • Efforts to understand how the VHL protein regulates expression of hypoxia-inducible genes have revealed that the cellular levels of hypoxia-inducible transcription factors HIF1α and HIF2α are elevated in clear cell renal carcinoma cells lacking a functional VHL gene ( 6 ). (pnas.org)
  • Aberrant expression of the cullin 4A ( CUL4A ) gene is found in many tumor types, while mutations of the cullin 4B ( CUL4B ) gene are causally associated with human X-linked mental retardation. (frontiersin.org)
  • DDB1 is part of an E3 ligase complex that includes the cullin proteins Cul4A and Cul4B. (aacrjournals.org)
  • Although CUL7 and PARC are present only in chordates, other members of the cullin protein family are found in Drosophila melanogaster , Caenorhabditis elegans, Arabidopsis thaliana and yeast. (biomedcentral.com)
  • Finally, we identify the Golgi protein Grasp65 as a novel and physiologically relevant substrate of Cul7(Fbxw8) in the control of Golgi and dendrite morphogenesis in neurons. (nih.gov)
  • The cysteine-rich domain of synaptosomal-associated protein of 23 kDa (SNAP-23) regulates its membrane association and regulated exocytosis from mast cells. (bioportfolio.com)
  • Chk1 regulates cell cycle progression, in part, by phosphorylating the Cdc25A protein phosphatase ( 1 - 4 ). (aacrjournals.org)
  • In mammalian cell culture, this protein predominantly localizes to the cytoplasm. (nih.gov)
  • To this end we have undertaken genetic and biochemical studies to decipher mechanisms that regulate degradation of MCIP1 proteins. (ahajournals.org)
  • Interestingly, serum deprivation has been shown to regulate Merlin at the protein level, however, exactly how such condition affects Merlin remains elusive. (nih.gov)
  • In addition to regulating DNA replication and mitotic entry, Chk1 has also been shown to stabilize stalled replication forks when DNA replication is impeded, to regulate transcription through phosphorylation of histone H3, and to regulate DNA repair by phosphorylating the Fanconi anemia protein FANCE ( 8 , 10 - 12 ). (aacrjournals.org)
  • RSV has a linear single-stranded RNA genome encoding 11 proteins, 2 of which are nonstructural (NS1 and NS2). (asm.org)
  • The Chk1 protein kinase preserves genome integrity in normal proliferating cells and in cells experiencing replicative and genotoxic stress. (aacrjournals.org)
  • Chk1 is a serine/threonine protein kinase that functions to maintain genome integrity in normal cycling cells and in cells exposed to replicative and genotoxic stress ( 1 , 2 ). (aacrjournals.org)