• The von Hippel-Lindau tumour suppressor protein (pVHL) ubiquitinates hypoxia-inducible factor 1α (HIF1α) when cell oxygen levels are normal. (wikipedia.org)
  • Mus musculus von Hippel-Lindau tumor suppressor (Vhl), mRNA. (genscript.com)
  • Researchers at the Goethe University Frankfurt, Heidelberg University, the German Cancer Research Center (DKFZ), Heidelberg University Hospital and the University Hospital in Jena have now discovered how the von Hippel-Lindau tumour suppressor protein (pVHL) intervenes in this signalling pathway. (goethe-university-frankfurt.de)
  • Here we demonstrate a critical role for the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL in HIF-1 regulation. (ncl.ac.uk)
  • The Von Hippel-Lindau tumor suppressor also known as pVHL is a protein that, is encoded by the VHL gene. (standardofcare.com)
  • Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic neoplastic disorder caused by germline mutation or deletion of the VHL gene, characterized by the tendency to develop multisystem benign or malignant tumors. (biomedcentral.com)
  • The VHL tumor suppressor gene is the gene for both von Hippel-Lindau disease as well as sporadic, clear-cell renal carcinoma. (nih.gov)
  • We have recently developed an improved method of detecting germline mutations in the von Hippel-Lindau disease tumor suppressor gene. (nih.gov)
  • As in von Hippel-Lindau syndrome, when the VHL protein is altered, the HIF-2α protein is not broken down, and instead builds up in cells. (medlineplus.gov)
  • Von Hippel-Lindau disease manifests in the third to fourth decades of life, depending on the location of the tumors. (eyewiki.org)
  • Under normal conditions, von Hippel-Lindau tumor suppressor pVHL ubiquitinates HIF for degradation. (eyewiki.org)
  • von Hippel-Lindau (VHL) disease, or von Hippel-Lindau syndrome, is a rare genetic disorder characterized by visceral cysts and benign tumors in multiple organ systems that have subsequent potential for malignant change. (medscape.com)
  • The resultant 2 encoded von Hippel-Lindau protein (pVHL) products, a 30-kD full-length form (p30) and a 19-kD form (p19), shuttle between the nucleus and the cytoplasm, where they form complexes with other proteins. (medscape.com)
  • In renal carcinoma cells that are defective for the von Hippel-Lindau (VHL) tumor suppressor, up-regulation of these CAs is associated with loss of regulation by hypoxia, consistent with the critical function of pVHL in the regulation of HIF-1. (ox.ac.uk)
  • Dr Xinlai Cheng and his colleagues at the Goethe University Frankfurt have discovered how a tumour suppressor known as pVHL influences signal transmission involving TGF-β. (goethe-university-frankfurt.de)
  • These VHL alterations lead to a predisposition to a somatic second hit, causing of a variety of tumors and fluid filled cysts, sporadic tumors, such as cerebellar hemangioblastoma, pheochromocytoma, clear cell renal cell carcinoma, familial erythrocytosis type two, that result in increased expression of HIF target genes. (standardofcare.com)
  • Germline mutations in the VHL gene predispose individuals to a variety of tumors, including renal carcinoma, CNS hemangioblastoma, islet cell tumors of the pancreas, and pheochromocytoma. (nih.gov)
  • Mutations in the tumor suppressor gene VHL cause the disease, which commonly manifests as a variety of tumors such as hemangioblastomas of the retina and brain as well as renal cell carcinoma. (eyewiki.org)
  • In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site. (standardofcare.com)
  • We observed gain of functions in VHL mutations, thereby stabilizing HIF2α protein and reprograming HIF2α genome-wide target gene transcriptional programs. (biomedcentral.com)
  • Together, our findings highlight the crucial role of pVHL-HIF dysregulation in VHL disease and strengthen the clinical relevance and significance of the missense mutations of Ser65 residue in pVHL in the familial VHL disease. (biomedcentral.com)
  • Cancer is a complex genetic disease caused by abnormal alteration (mutations) in DNA sequences that leads to dyregulation of normal cellular processes thereby driving tumor growth. (intechopen.com)
  • Herein we selected a Mendelian genetics form of familial cancer such as hereditary tumor syndromic endocrine neoplasias caused by highly penetrant germline mutations leading to pheochromocytoma-paraganglioma syndromes. (intechopen.com)
  • Multiple endocrine neoplasia syndrome type 1 (MEN-1), loss-of-function germline mutations in the tumor suppressor gene MEN1 increase the risk of developing pituitary, parathyroid and pancreatic islet tumors, and less commonly thymic carcinoids, lipomas and benign adrenocortical tumors. (intechopen.com)
  • In the case of multiple endocrine neoplasia type 2 (MEN 2), gain-of-function germline mutations clustered in specific codons of the RET proto-oncogene increase the risk of developing medullary thyroid carcinoma (MTC), phaeochromocytoma and parathyroid tumors. (intechopen.com)
  • Mutations in the VHL gene increase the risk of developing tumors of the nervous system called paragangliomas or pheochromocytomas (a type of paraganglioma). (medlineplus.gov)
  • Other spontaneous mutations found in this condition, called somatic mutations, are acquired during a person's lifetime and are present only in the tumor cells. (medlineplus.gov)
  • The VHL gene mutations found in nonsyndromic paraganglioma or pheochromocytoma change single amino acids in the VHL protein or create an abnormally short protein. (medlineplus.gov)
  • The other VHL gene mutations that can cause familial erythrocytosis also change single amino acids in the VHL protein. (medlineplus.gov)
  • However, 20% of mutations are de novo, and diagnosis for patients with a negative family history is confirmed with the occurrence of two VHL-related tumors and at least one retinal hemangioblastoma [3] . (eyewiki.org)
  • Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions. (frontiersin.org)
  • pVHL and HIF alpha-subunits co-immunoprecipitate, and pVHL is present in the hypoxic HIF-1 DNA-binding complex. (ncl.ac.uk)
  • Cells with abnormal pVHL are unable to disrupt formation of these dimers, and behave like they are hypoxic even in oxygenated environments. (standardofcare.com)
  • Low ATP concentrations in hypoxic tumour cells disable the apoptotic cascade and induce cell death by necrosis. (bmj.com)
  • These studies define a new class of HIF-1-responsive gene, the activation of which has implications for the understanding of hypoxic tumor metabolism and which may provide endogenous markers for tumor hypoxia. (ox.ac.uk)
  • I identified several potentially suppressive myeloid cell subsets, including TAMs and arginase-1ʰⁱ monocytic-MDSCs (M-MDSCs) that expand during CD8⁺ T cell-mediated tumor regression and subsequent recurrence, which may play a role in tumor regrowth. (ubc.ca)
  • There the SMAD proteins mediate the extent to which genes are activated and translated into proteins and other gene products. (goethe-university-frankfurt.de)
  • The VHL syndrome, generally caused by hereditary allele inactivation plus a tissue somatic mutation, is characterized by the occurrence of malignancies and increased expression of oncogenic genes, including VEGF, that allow tumor development and progression. (standardofcare.com)
  • This heterodimer of HIF activates genes that encode for proteins such as vascular endothelial growth factor (VEGF) and erythropoietin, proteins that are both involved in angiogenesis. (standardofcare.com)
  • The VHL protein likely plays a role in other cellular functions, including the regulation of other genes and control of cell division. (medlineplus.gov)
  • A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. (biomedcentral.com)
  • The transcriptional complex hypoxia-inducible factor-1 (HIF-1) has emerged as an important mediator of gene expression patterns in tumors, although the range of responding genes is still incompletely defined. (ox.ac.uk)
  • USP20 is known to deubiquitinate a number of proteins including thyronine deiodinase type 2 (D2), Hypoxia-inducible factor 1α (HIF1α), and β2 adrenergic receptor (β2AR). (wikipedia.org)
  • The process of the degradation of the hypoxia-inducible factors (HIFs) that mainly regulate oxygen and iron dependent activity of enzymes require DHL tumor suppressor. (standardofcare.com)
  • During hypoxia, the proline residues are not hydroxylated and pVHL cannot bind. (standardofcare.com)
  • The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. (bmj.com)
  • One of the targets of the VCB-CUL2 complex is a protein called hypoxia-inducible factor 2-alpha (HIF-2α). (medlineplus.gov)
  • One proposed mechanism of tumorigenesis for VHL involves the regulatory effect pVHL has on hypoxia-inducible factors (HIF). (eyewiki.org)
  • However, a lack of pVHL such as in VHL disease or hypoxia leads to stabilization of HIF-α and increased expression of tumorigenic molecules such as vascular endothelial growth factor (VEGF), platelet- derived growth factor peptide (PDGF), and transforming growth factor (TGF-a) [4] . (eyewiki.org)
  • NDRG3 protein levels increased in multiple cell types in response to hypoxia and were correlated with increased angiogenesis, anti-apoptotic, motility and proliferative (but not metabolic) gene expression. (bhdsyndrome.org)
  • A critical role in these processes was confirmed when reduction in NDRG3 abolished the hypoxia-induced expression of pro-angiogenic factors, increased cellular apoptosis under prolonged hypoxia and decreased tumour cell growth. (bhdsyndrome.org)
  • However, this self-sufficient mechanism that enables recovery from hypoxia, can also be used by tumour cells enabling continued growth. (bhdsyndrome.org)
  • Hypoxia-inducible expression of tumor-associated carbonic anhydrases. (ox.ac.uk)
  • Both CA9 and CA12 were strongly induced by hypoxia in a range of tumor cell lines. (ox.ac.uk)
  • Further studies of CA9 defined a HIF-1-dependent hypoxia response element in the minimal promoter and demonstrated that tight regulation by the HIF/pVHL system was reflected in the pattern of CA IX expression within tumors. (ox.ac.uk)
  • VHL disease encompasses various types of tumors, including retinal or central nervous system hemangioblastoma (RH or CNSH), clear cell renal cell carcinoma (RCC), pheochromocytoma (PHE), multiple pancreatic cysts or tumors (PCT), epididymal or broad ligament cystadenomas and endolymphatic sac tumor. (biomedcentral.com)
  • Clinical hallmarks of VHL disease include the development of retinal and central nervous system (CNS) hemangioblastomas (blood vessel tumors), pheochromocytomas , multiple cysts in the pancreas and kidneys, and an increased risk for malignant transformation of renal cysts into renal cell carcinoma. (medscape.com)
  • Both computed tomography (CT) and magnetic resonance imaging (MRI) will reveal large tumors expanding into the temporal bones for endolymphatic sac tumors (ELST) [7] . (eyewiki.org)
  • Tumour suppressors are proteins whose defects or reduced presence in multicellular organisms are associated with a high risk that cells will degenerate into tumour cells. (goethe-university-frankfurt.de)
  • His mentor, Professor Stefan Wölfl, explained an important finding that emerged from the new-found connection between pVHL and the TGF-β signalling pathway: "pVHL is known to be involved in how cells 'feel' oxygen and react to varying oxygen availability. (goethe-university-frankfurt.de)
  • Tumour cells are good at adapting to their environment inside the organism and to variations in oxygen availability. (goethe-university-frankfurt.de)
  • In cells exposed to iron chelation or cobaltous ions, HIF-1 is dissociated from pVHL. (ncl.ac.uk)
  • Studies found that cGMP may up/downregulate the growth of certain endocrine tumor cells, suggesting that PDE5i could impact cancer risk. (bvsalud.org)
  • These compounds generally penetrate cell membranes, act on specific target proteins in cells, regulate intracellular signaling pathways, and cause some changes in cell phenotype. (chemscene.com)
  • The VHL protein is found both in the nucleus and in the cytosol of transiently transfected cells. (nih.gov)
  • Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells. (medlineplus.gov)
  • Based on this function, the VHL protein is classified as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. (medlineplus.gov)
  • The VHL protein is also involved in the formation of the extracellular matrix, which is an intricate lattice that forms in the spaces between cells and provides structural support to tissues. (medlineplus.gov)
  • Low power image-A. This retinal tumor shows high vessel density with thick walls (arrow) and cyst containing proteinaceous material (asterisk) High power image-B. The stromal cells are foamy and vacuolated (arrowheads) with many small channels resembling capillaries (arrows). (eyewiki.org)
  • The foamy stromal cells between the capillaries stain positive for glial fibrillary acid protein and neuron-specific enolase. (medscape.com)
  • These cellular components can include cells of the innate immune system, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and eosinophils, as well as cells of the adaptive immune system, including CD4⁺ T regulatory cells (Tregs) and cytotoxic CD8⁺ T cells. (ubc.ca)
  • The aim of this thesis work is to interrogate the pro- and anti- tumorigenic roles myeloid cells play in primary and metastatic disease, and how these myeloid populations interact with cells of the adaptive immune system to influence anti-tumor immunity. (ubc.ca)
  • In Chapter 2, I examined how proteins secreted by cancer cells can promote a tumor-permissive microenvironment through the recruitment of suppressive innate and adaptive immune cells to the lungs. (ubc.ca)
  • I demonstrated that tumor cells secreted proteins that drove the recruitment and/or expansion of pulmonary TAMs, Tregs, and granulocytic-MDSCs (G-MDSCs), resulting in increased primary lung tumor growth and pulmonary metastasis of mammary carcinoma cells, respectively. (ubc.ca)
  • Targeting tumor-secreted proteins, or the suppressive immune cells that are expanded in response to said proteins, led to a decrease in primary and metastatic pulmonary disease. (ubc.ca)
  • I demonstrated that using glucose restriction of CD8⁺ T cells in vitro led to improved tumor regression in vivo. (ubc.ca)
  • This thesis work aims to examine the diverse phenotype and function of myeloid cells in primary and metastatic disease, ultimately contributing to an improved understanding of the interplay between the innate and adaptive immune system in the solid tumor microenvironment. (ubc.ca)
  • A small proportion of these tumors show large ducts lined by neoplastic cells, the so-called large-duct variant of adenocarcinoma. (coek.info)
  • Cells express a pool of thousands of different proteins that need to be tightly controlled for proper cellular structure, organization, and function. (hindawi.com)
  • The pVHL/HIF-1 interaction provides a new focus for understanding cellular oxygen sensing. (ncl.ac.uk)
  • This keynote address will describe new drugs emerging from studies of the VHL tumor suppressor protein (pVHL), which is usually defective in clear cell renal cell carcinomas (ccRCCs). (aspet.org)
  • Sporadic mutation in the second copy of the VHL protein can lead to carcinomas, in particular hemangioblastomas affecting the liver and kidneys, renal and vaginal clear cell adenocarcinomas. (standardofcare.com)
  • Generalized up-regulation of CA IX in VHL-associated renal cell carcinoma contrasted with focal perinecrotic expression in a variety of non-VHL-associated tumors. (ox.ac.uk)
  • Triphasic pancreatic-protocol computed tomography is the best initial diagnostic test for pancreatic cancer, and on this modality these tumors appear as a hypodense solid mass. (coek.info)
  • The availability of tools to interrogate the transcriptome and proteome, such as expression profiling, have identified a substantial library of products that could aid in distinguishing a well-differentiated pancreatic carcinoma from a benign pancreatic lesion.2 Many of these proteins can be detected immunohistochemically and are thus available to the practicing pathologist (Table 2).3 Some of these markers have been validated on biopsy specimens as well. (coek.info)
  • Although individualized targeted therapies are routinely used for patients with lung and breast tumors, personalized medicine has not achieved the same degree of success in the pancreas. (coek.info)
  • Retinal hemangioblastoma, fundus photo A-C, Fluorescein Angiography D. A. Observe the tortuous and dilated artery (feeder) and vein exiting through optic nerve head (draining), as well as the protruding retinal tumor with orange-yellow color present in the B. peripheral and C. optic nerve, with macular traction. (eyewiki.org)
  • Germline heterozygous mutation of the VHL tumor suppressor gene, located on 3p25.3, encoding VHL tumor suppressor protein (pVHL), has been identified as the leading cause of VHL disease. (biomedcentral.com)
  • pVHL forms a ubiquitin ligase that targets the alpha subunits of the HIF transcription factor for proteasomal degradation provided they are prolyl hydroxylated by the oxygen-sensitive EglN (also called PHD) 2-oxoglutarate (2-OG)-dependent dioxygenases. (aspet.org)
  • The main action of the VHL protein is ubiquitin ligase activity resulting in protein degradation. (standardofcare.com)
  • pVHL is best known as the substrate-binding subunit of an E3 ubiquitin ligase, which binds the transcription elongation factors C and B (elongin C/B) forms the VCB complex, then interacts with Cullin-2 (CUL2) and the RING finger protein RBX1 forming the VCB-CR complex(3). (biomedcentral.com)
  • The solid tumor microenvironment contains structural and cellular components that can dictate cancer progression and therapy response. (ubc.ca)
  • Type 1 VHL has a low risk of pheochromocytomas, but both subtypes present with multiple organ tumors [5] . (eyewiki.org)
  • These findings indicate that the interaction between HIF-1 and pVHL is iron dependent, and that it is necessary for the oxygen-dependent degradation of HIF alpha-subunits. (ncl.ac.uk)
  • In addition to the regulation of HIF1α, pVHL regulates USP20. (wikipedia.org)
  • The central dogma in the study of protein folding suggests that the thermodynamically-favorable state of proteins under physiological conditions is their folded one. (tau.ac.il)
  • USP20 binds to the β-domain of pVHL and is subsequently ubiquitinated. (wikipedia.org)
  • The CSN subunit, CSN5, binds both the CODD of HIF-1α and the pVHL tumor suppressor. (elsevierpure.com)
  • If we could, for example, use a substance to specifically regulate pVHL activity, we would also influence the TGF-β signalling pathway, which in turn plays a major role in the formation of tumours, and metastases in particular," says Xinlai Cheng. (goethe-university-frankfurt.de)
  • These nutrient-driven post-translational modifications are highly altered in cancer and regulate protein functions in various cancer-associated processes. (biomedcentral.com)
  • reported increased levels of NDRG3 and ERK1/2 signalling molecules in engrafted tumours and patient hepatocellular carcinoma samples (n=25/103) supporting a role in tumour development. (bhdsyndrome.org)
  • Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules. (biomedcentral.com)
  • Given the importance of pVHL in NDRG3 regulation, the NDRG3-Raf-ERK signalling pathway could also be playing a role in VHL-associated tumourigenesis. (bhdsyndrome.org)
  • Stained liver tissue shows the complementary occurrence of pVHL and SMAD proteins: Where pVHL (green) is abundant, SMAD2/3 (red) is scarce, and vice versa. (goethe-university-frankfurt.de)
  • Diagnosis is confirmed with a positive familial history and at least one VHL-related tumor [3] . (eyewiki.org)
  • A diagnosis of familial VHL requires a positive family history of disease in addition to one VHL-associated tumor [3] . (eyewiki.org)
  • Further, our study demonstrates that repression of key effector proteins in the post-transcriptional miRNA pathway impairs primary cilium formation. (biomedcentral.com)
  • If the proteins involved in ER-phagy are defective, neurodegenerative diseases result. (bmls.de)
  • Nevertheless, in neurodegenerative diseases these proteins accumulate with disastrous consequences for neurons, eventually leading to cell death. (5dok.org)
  • Loss of heterozygosity at a locus on chromosome 8 in a high percentage of tumors from patients with prostate carcinoma has been detected and the area of minimal deletion on chromosome 8p12-21 determined. (nih.gov)
  • The VHL gene is located on chromosome 3p35 and encodes the pVHL protein [6] [4] . (eyewiki.org)
  • Ageing leads to a gradual dysfunction of the proteostasis network and thus to proteome instability due to accumulation of damaged and/or misfolded proteins [ 2 ]. (hindawi.com)
  • Thus the formation of aggregates renders these toxic proteins resistant to proteasomal degradation and initiates the accumulation of polyGln proteins and polyGln-interacting proteins. (5dok.org)
  • The ubiquitin-proteasome system (UPS) is the main pathway in the cell for the elimination of aberrant or misfolded proteins. (5dok.org)
  • These studies focus on the degradation of specific disease related proteins and the general status of the UPS under conditions of an excess of aberrant or misfolded proteins. (5dok.org)
  • Early identification affected individuals with asymptomatic VHL disease-associated tumors and mutation carriers via genetic recognition and rational medical interventions would improve patients' survival rates and quality of life. (biomedcentral.com)
  • These genetic changes are thought to have similar effects on protein function to those of the Arg200Trp mutation. (medlineplus.gov)
  • Transforming Growth Factor beta (TGF-β) is a signalling protein whose dysregulation can cause developmental disorders and cancer. (goethe-university-frankfurt.de)
  • Inside the cell, the TGF-β receptors in their turn activate a protein called SMAD3, which then forms complexes with SMAD4 that translocate to the cell nucleus. (goethe-university-frankfurt.de)
  • In the Journal of Cell Biology the scientists report the first evidence that pVHL degrades the SMAD3 protein. (goethe-university-frankfurt.de)
  • In the normal cell with active VHL protein, HIF alpha is regulated by hydroxylation in the presence of oxygen. (standardofcare.com)
  • This complex targets other proteins to be broken down (degraded) by the cell when they are no longer needed. (medlineplus.gov)
  • Degradation, known as ER-phagy, is promoted by the protein ubiquitin, which controls many processes in the cell. (bmls.de)
  • The hexosamine biosynthetic pathway (HBP) and its end product uridine diphosphate N-acetyl glucosamine (UDP-GlcNAc) are important regulators of cell signaling that favor tumor promotion. (biomedcentral.com)
  • In Chapter 4, I profiled the dynamic myeloid compartment following antigen specific CD8⁺ T cell-mediated tumor regression and recurrence. (ubc.ca)
  • Here, I investigate the role of one intrinsic factor (receptor-type protein tyrosine phosphatase alpha) and one extrinsic factor (ionizing radiation) in facilitating cancer cell invasion. (ubc.ca)
  • Receptor-type protein tyrosine phosphatase alpha (PTPα is a widely expressed transmembrane-bound protein that has been implicated in integrin signaling, focal adhesion formation, and normal cell migration. (ubc.ca)
  • Re-expression of pVHL restored oxygen-dependent instability. (ncl.ac.uk)
  • The VHL syndrome is inherited by one mutation in the VHL protein that causes the protein's normal function to be lost or altered. (standardofcare.com)
  • The mutation changes a single protein building block (amino acid) in the VHL protein, replacing the amino acid arginine with the amino acid tryptophan at position 200 (written as Arg200Trp or R200W). (medlineplus.gov)
  • This mutation disrupts the function of the VHL protein, particularly its ability to target HIF-2α to be broken down. (medlineplus.gov)
  • Oxygen-dependent hydroxylation of HIF-1α and HIF-2α by prolyl hydroxylase domain (PHD) enzymes and ubiquitination by pVHL results in proteosomal degradation inhibiting HIF signalling. (bhdsyndrome.org)
  • Tumors involving other organs and the CNS (brain, spinal cord) are present in 25% of patients with VHL disease. (medscape.com)
  • Hydroxylation of HIF creates a binding site for pVHL,the protein product of the VHL gene. (standardofcare.com)
  • High CSN5 expression generates a pVHL-independent form of CSN5 that stabilizes HIF-1α aerobically by inhibiting HIF-1α prolyl-564 hydroxylation. (elsevierpure.com)
  • This suggests that at a very early stage in evolution pVHL assumed the regulatory function that we have now brought to light. (goethe-university-frankfurt.de)
  • We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. (biomedcentral.com)
  • A putative nuclear localization signal, a nuclear export signal, and a cytoplasmic retention locus have been identified in the VHL protein. (nih.gov)
  • UDP-GlcNAc is then used for N-linked and O-linked glycosylation in the ER and Golgi and for O-GlcNAc modification of nuclear and cytoplasmic proteins by OGT (O-GlcNAc transferase). (biomedcentral.com)
  • The catalytic site of USP20, like other DUBs, contains conserved cysteine and histidine residues that catalyse the proteolysis of an isopeptide bond between a lysine residue of a target protein and a glycine residue of a ubiquitin molecule. (wikipedia.org)
  • USP20 belongs to the USP group and, like most DUBs, catalyse the breakage of an isopeptide bond between a lysine residue of the target protein and the terminal glycine residue of a ubiquitin protein. (wikipedia.org)
  • The histidine molecule is protonated by the cysteine residue and this allows the cystein residue to undergo a nucleophilic attack on the isopeptide bond, which removes the ubiquitin from the substrate protein. (wikipedia.org)
  • G) substitution at residue 65 of VHL protein (p.Ser65Pro and Ser65Trp). (biomedcentral.com)
  • After translation, where is a protein localised, and what complexes should it join? (biomedcentral.com)
  • He will describe their recent efforts to identify new cancer targets based on synthetic lethality and to find protein degraders for "undruggable" oncoproteins. (aspet.org)
  • A proportion of tumors are poorly differentiated with little or no gland formation. (coek.info)
  • Immunofluorescence studies show Hs-CUL-2 to be a cytosolic protein that can be translocated to the nucleus by pVHL. (nih.gov)
  • Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. (cusabio.com)
  • HIF-2α is one part (subunit) of a larger protein complex called HIF, which plays a critical role in the body's ability to adapt to changing oxygen levels. (medlineplus.gov)
  • In our lab we utilize a variety of biochemical, biophysical and molecular biology methodologies to study the mechanism and significance of protein unfolding and misfolding. (tau.ac.il)
  • The VHL protein has been shown to bind tightly and specifically to the Elongin B and C subunits and to inhibit Elongin (SIII) transcriptional activity in vitro . (nih.gov)
  • Recently, Hs-CUL-2, a member of the recently identified multigene family, the cullins, has been shown to specifically associate with the trimeric pVHL-elongin B-C (VBC) complex in vitro and in vivo . (nih.gov)
  • HIF is necessary for tumor growth. (standardofcare.com)
  • Glucose, glutamine, fatty acids, and amino acids are the primary drivers of tumor growth and act as substrates for the hexosamine biosynthetic pathway (HBP). (biomedcentral.com)
  • Here we show that the tumor-associated carbonic anhydrases (CAs) are tightly regulated by this system. (ox.ac.uk)