• The Von Hippel-Lindau tumor suppressor also known as pVHL is a protein that, is encoded by the VHL gene. (standardofcare.com)
  • In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site. (standardofcare.com)
  • Hydroxylation of HIF creates a binding site for pVHL,the protein product of the VHL gene. (standardofcare.com)
  • pVHL directs the ubiquitylation of HIF1A, ensuring that this protein will be degraded by the proteasome. (standardofcare.com)
  • Here we demonstrate a critical role for the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL in HIF-1 regulation. (ncl.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)
  • 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)
  • In the Journal of Cell Biology the scientists report the first evidence that pVHL degrades the SMAD3 protein. (goethe-university-frankfurt.de)
  • 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)
  • 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 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)
  • Immunofluorescence studies show Hs-CUL-2 to be a cytosolic protein that can be translocated to the nucleus by pVHL. (nih.gov)
  • The VHL gene is located on chromosome 3p35 and encodes the pVHL protein [6] [4] . (eyewiki.org)
  • Under normal conditions, von Hippel-Lindau tumor suppressor pVHL ubiquitinates HIF for degradation. (eyewiki.org)
  • 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)
  • We describe areas where major inroads were initially achieved by targeting angiogenesis and by unraveling pathways in the heterogeneous tumors of mesenchymal origin-spurred by the identification of c-Kit-activating mutations in GIST and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). (cancernetwork.com)
  • Here, in Part I, we describe areas where major inroads were initially achieved by targeting angiogenesis (central to the biology of renal cell carcinoma and hepatocellular cancer) and by unraveling pathways in the heterogeneous tumors of mesenchymal origin-spurred by the identification of c-Kit-activating mutations in gastrointestinal stromal tumors (GIST) and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). (cancernetwork.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)
  • The mechanisms of such suppression include: deletion of one or both alleles, gene inactivation by mutations (commonly observed in sporadic tumors) or promoter hypermethylation (3, 5). (czytelniamedyczna.pl)
  • Mutations of the VHL gene are associated with Von Hippel-Lindau disease. (standardofcare.com)
  • Either at genomic or at proteomic level, mutations have significant impact on normal gene or protein function, and human diseases could be associated with mutations like nonsynonymous single-nucleotide variations (nsSNVs) on amino acids. (hindawi.com)
  • Yet how gene mutations affect protein activities through posttranslational modification sites have not been widely studied. (hindawi.com)
  • We observed gain of functions in VHL mutations, thereby stabilizing HIF2α protein and reprograming HIF2α genome-wide target gene transcriptional programs. (biomedcentral.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)
  • We have recently developed an improved method of detecting germline mutations in the von Hippel-Lindau disease tumor suppressor gene. (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)
  • 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)
  • For example, studies suggest that ccRCC is closely associated with tumor suppressor von-Hippel Lindau ( VHL ) gene mutations that lead to stabilization of hypoxia inducible factors (HIF-1 α and HIF-2 α , also known as HIF1A and EPAS1) in both sporadic and familial forms [ 5 , 6 ]. (hindawi.com)
  • 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)
  • Hypoxia is the most common characteristic in the microenvironment of solid tumors because tumor progression and metastasis depend on the ability of cancer cells to initiate angiogenesis and ensure the delivery of oxygen and nutrients ( 11 , 12 ). (jcancer.org)
  • The progression risk of ccRCC remains difficult to predict particularly for tumors with organ-confined stage and intermediate differentiation grade. (uzh.ch)
  • By applying graphical log-linear modeling for over 700 ccRCC for which the molecular parameters were available, only a weak conditional dependence existed between the expression of p27, PTEN, CAIX, and p-S6, suggesting that the dysregulation of several independent pathways are crucial for tumor progression. (uzh.ch)
  • 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)
  • PURPOSE: Tumor hypoxia modifies treatment efficacy and promotes tumor progression. (ox.ac.uk)
  • During the progression of colitis, genetic alterations associated with mucosal permeability [ e.g. those in extracellular matrix protein 1 ( ECM1 ), cadherin 1 ( CDH1 ), and hepatocyte nuclear factor 4 alpha ( HNF4A )] have been observed and considered to confer the risk of severe UC ( 11 , 12 ). (iiarjournals.org)
  • In addition, VHL-mutated tumors showed an unexpected overexpression of EglN3 mRNA that did not lead to significantly different EglN3 protein levels. (nih.gov)
  • The one editing site of FLNA pre-mRNA is located within amino acid 2341 of the final protein. (wikipedia.org)
  • Mus musculus von Hippel-Lindau tumor suppressor (Vhl), mRNA. (genscript.com)
  • 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)
  • mRNA amounts correlated favorably with mRNA degrees of AB-hydrolase domain name made up of-5, an activator of ATGL, and adversely with mRNA degrees of lipid droplet proteins, perilipin, and Suggestion47 in human being subcutaneous adipose cells. (bioskinrevive.com)
  • Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling. (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)
  • Nevertheless, when we compared VHL tumors with SDHB cases, which often exhibit a malignant behavior, we found that HIF-1α target genes showed a predominant activation in the VHL PCCs. (nih.gov)
  • Expression data from 67 HIF target genes was sufficient to cluster SDHB and VHL tumors into two different groups, demonstrating different pseudo-hypoxic signatures. (nih.gov)
  • The VHL protein likely plays a role in other cellular functions, including the regulation of other genes and control of cell division. (medlineplus.gov)
  • 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)
  • There the SMAD proteins mediate the extent to which genes are activated and translated into proteins and other gene products. (goethe-university-frankfurt.de)
  • Genes newly defined as targets of the VHL/hypoxia pathway (conditionally downregulated by VHL in normoxic cells) include aminopeptidase A, collagen type V, alpha 1, cyclin G2, DEC1/Stra13, endothelin 1, low density lipoprotein receptor-related protein 1, MIC2/CD99, and transglutaminase 2. (ox.ac.uk)
  • These genes have a variety of functions relevant to tumour biology. (ox.ac.uk)
  • Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. (biomedcentral.com)
  • EXPERIMENTAL DESIGN: We performed linear discriminant analysis, a machine learning algorithm, on the NCI-60 cancer cell line microarray expression database to identify a gene profile that best distinguish cell lines with high Von-Hippel Lindau (VHL) gene expression, an important regulator of hypoxia-related genes, from those with low expression. (ox.ac.uk)
  • In hypoxic conditions, or in the presence of a deactivating VHL mutation HIF1alpha and other protein players initiate transcription of pro angiogenic genes. (the-scientist.com)
  • The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. (hindawi.com)
  • In addition, a PPI network can be modeled as an undirected graph, where vertices represent proteins and edges represent interactions between proteins, to prioritize disease associated genes or pathways and to understand the modus operandi of disease mechanisms [ 9 , 10 ]. (hindawi.com)
  • For each cancer discussed in the first part of our overview, as well as in Part II, which will deal with more common cancers, we briefly cover the tumor biology, how targeting was achieved, the introduction of immune modulation or immune-conjugates, and the impact these therapies are having in the disease. (cancernetwork.com)
  • However protein activities are closer to disease activities. (hindawi.com)
  • A nice linkurl:AP story;http://hosted.ap.org/dynamic/stories/H/HATFIELD_MCCOY_SECRET?SITE=PASTR&SECTION=HOME&TEMPLATE=DEFAULT talks about the hypothesis that much of the fuel for the famed Hatfield-McCoy feud might be attributed to Von Hippel-Lindau disease, a rare genetic disorder that predisposes those affected to highly-vascularized tumors. (the-scientist.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)
  • 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)
  • Clear cell RCC is associated with von Hippel-Lindau (VHL) disease. (renalandurologynews.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)
  • They include tuberous sclerosis complex, Sturge-Weber syndrome , von Hippel-Lindau disease, and neurofibromatosis. (medscape.com)
  • Von Hippel-Lindau Syndrome (VHL) is a rare, autosomal dominant, familial neoplastic disease that affects the central nervous system and multiple organs such as the kidneys, pancreas, adrenals, and reproductive organs. (eyewiki.org)
  • Von Hippel-Lindau disease manifests in the third to fourth decades of life, depending on the location of the tumors. (eyewiki.org)
  • Von Hippel-Lindau disease can be split into two subtypes, Type 1 and Type 2, depending on the presence of pheochromocytomas [5] . (eyewiki.org)
  • Definitive diagnosis of Von Hippel-Lindau disease occurs in one of two ways. (eyewiki.org)
  • A diagnosis of familial VHL requires a positive family history of disease in addition to one VHL-associated tumor [3] . (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)
  • 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)
  • Tumors involving other organs and the CNS (brain, spinal cord) are present in 25% of patients with VHL disease. (medscape.com)
  • Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells. (medlineplus.gov)
  • PHDs hydroxylate conserved prolyl residues from the HIF-1 and HIF-2 subunits, hence marketing their binding towards the von Hippel Lindau (VHL) tumor suppressor proteins, which goals HIF isoforms for proteasomal degradation in normoxia (21C24). (bioskinrevive.com)
  • 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)
  • The main action of the VHL protein is ubiquitin ligase activity resulting in protein degradation. (standardofcare.com)
  • Ubiquitin tagging alters protein fates, often marking substrates for degradation. (rupress.org)
  • MDM2, an E3 that induces the degradation of the p53 tumor suppressor protein, also became fixed in the nucleolus in response to actinomycin-D treatment, which is known to block p53 ubiquitylation.The authors propose that such nucleolar sequestration, and more generally the concept of switching proteins between a mobile and static state, is likely to be a commonly used mechanism for regulating enzyme reactions. (rupress.org)
  • Cermakova K, Hodges HC: "Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation. (antikoerper-online.de)
  • Li X, Song Y: "Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy. (antikoerper-online.de)
  • The VHL protein sequenced by this gene was found to complex with the hypoxia-inducible factor (HIF-1) to promote the degradation of HIF-1. (renalandurologynews.com)
  • Measuring protein phosphorylation and expression in glioblastoma cells across 40 signaling pathway nodes in response to different drugs and for different oxygen tensions revealed that SHP2 antagonism has network-level, context-dependent signaling consequences that affect cell phenotypes (e.g., cell death) in unanticipated ways. (aacrjournals.org)
  • To study the potential role in this metabolic shift of von Hippel-Lindau (VHL), a protein component of a ubiquitin ligase complex, the authors generated nephron progenitor cell-specific VHL knockout mice. (lww.com)
  • a protein component of a ubiquitin ligase complex) and hypoxia-inducible factors (a family of transcription factors activated by hypoxia). (lww.com)
  • Following modification HIF- alpha chains are captured by a ubiquitin ligase E3 complex containing the von Hippel-Lindau (VHL) tumour suppressor protein. (ox.ac.uk)
  • The von Hippel-Lindau tumour suppressor gene (VHL) targets hypoxia inducible factor (HIF)-alpha subunits for ubiquitin dependent proteolysis. (ox.ac.uk)
  • Regulation of the process occurs at the level of the ubiquitin ligases, called E3s, which facilitate the transfer of ubiquitin from a conjugating enzyme to the target protein. (rupress.org)
  • The ubiquitin-proteasome pathway: on protein death and cell life. (antikoerper-online.de)
  • The receptor has an unusual composition in that it shares some structural similarities with G-PROTEIN-COUPLED RECEPTORS and functions as an ubiquitin protein ligase when internalized. (uams.edu)
  • 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)
  • Through careful study of the cytogenetics of VHL patients, the gene at this locus was found to be a tumor suppressor gene associated with familial clear cell carcinomas as well as a large majority of sporadic RCC. (renalandurologynews.com)
  • Why and how it is replacing past approaches in the management of solid tumors is the subject of this two-part overview. (cancernetwork.com)
  • The situation with solid tumors is considerably more complex, and the evolution of targeted therapies for these cancers is still in its infancy. (cancernetwork.com)
  • At present, and for some years to come, the treatment of most solid tumors will continue to rely on a patchwork of empirically derived and newly introduced molecularly targeted agents. (cancernetwork.com)
  • phaos = light, literally meaning "tumor of lenses" after the retinal hamartomas that would eventually be recognized as part of constellation of findings now recognized as tuberous sclerosis complex. (medscape.com)
  • 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)
  • 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)
  • Pheochromocytomas are a feature of von Hippel-Lindau syndrome, but they and other paragangliomas can also occur nonsyndromically (without the other signs and symptoms of the syndrome). (medlineplus.gov)
  • Metastatic pheochromocytomas and paragangliomas are rare and challenging tumors. (thieme-connect.com)
  • Type 1 VHL has a low risk of pheochromocytomas, but both subtypes present with multiple organ tumors [5] . (eyewiki.org)
  • Fuhrman grading was first described in 1982 and has been used to both describe renal tumors and make prognoses. (renalandurologynews.com)
  • Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and accounts for approximately 60% to 70% of all renal tumors [ 1 ]. (hindawi.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)
  • These genetic changes are thought to have similar effects on protein function to those of the Arg200Trp mutation. (medlineplus.gov)
  • 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 von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia. (ox.ac.uk)
  • EXPERIMENTAL DESIGN: Using tissue microarrays, expression patterns of 15 different proteins were evaluated in over 800 ccRCC patients to analyze pathways reported to be physiologically controlled by the tumor suppressors von Hippel-Lindau protein and phosphatase and tensin homologue (PTEN). (uzh.ch)
  • We postulate that co-ordinate regulation as part of the HIF pathway may explain this paradox, and that evolution of anti-apoptotic pathways may be required for tumour growth under VHL-dysregulation. (ox.ac.uk)
  • 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)
  • 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)
  • A total of 67% of patients received both prior anti-PD-1 (programmed cell death protein 1) and anti-VEGF (vascular endothelial growth factor) agents. (ascopost.com)
  • HIF-1 regulates production of multiple proteins, including vascular-endothelial growth factor (VEGF) and other cell regulatory proteins that are normally kept in check but which are significantly elevated in times of hypoxia, starvation, and stress. (renalandurologynews.com)
  • Diagnosis is confirmed with a positive familial history and at least one VHL-related tumor [3] . (eyewiki.org)
  • Proto-Oncogene Proteins c-mdm2" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)
  • This graph shows the total number of publications written about "Proto-Oncogene Proteins c-mdm2" by people in this website by year, and whether "Proto-Oncogene Proteins c-mdm2" was a major or minor topic of these publications. (umassmed.edu)
  • Below are the most recent publications written about "Proto-Oncogene Proteins c-mdm2" by people in Profiles. (umassmed.edu)
  • 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)
  • The Von Hippel-Lindau syndrome (VHL) is a dominantly inherited hereditary cancer syndrome. (standardofcare.com)
  • The Von Hippel-Lindau (VHL) tumor-suppressor protein is not functional in about 90% of patients with clear cell renal cell carcinoma, leading to accumulation of HIF proteins inside the tumor cell. (ascopost.com)
  • RESULTS: Patients with pT2 and pT3 tumors that were p27 and CAIX positive had a better outcome than those with all remaining marker combinations. (uzh.ch)
  • A prolonged survival among patients with intermediate grade (grade 2) correlated with both nuclear p27 and cytoplasmic PTEN expression, as well as with inactive, nonphosphorylated ribosomal protein S6. (uzh.ch)
  • To identify specific markers of CRT response, we compared pretreatment biopsies from LACC patients with pathological complete response (sensitive) with those from patients showing macroscopic residual tumor (resistant) after neoadjuvant CRT, using a proteomic approach integrated with gene expression profiling. (biomedcentral.com)
  • Here, we investigated the relationship between osteopontin (OPN), tumor pO(2), and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). (ox.ac.uk)
  • The relationships between plasma OPN levels, tumor pO(2) as measured by the Eppendorf microelectrode, freedom from relapse (FFR), and survival in HNSCC patients were evaluated. (ox.ac.uk)
  • CONCLUSIONS: Plasma OPN levels appeared to correlate with tumor hypoxia in HNSCC patients and may serve as noninvasive tests to identify patients at high risk for tumor recurrence. (ox.ac.uk)
  • Nme1 is found in human body fluids and its protein level correlates with prognosis in cancer patients. (unibo.it)
  • 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)
  • PURPOSE: Tumor stage and nuclear grade are the most important prognostic parameters of clear cell renal cell carcinoma (ccRCC). (uzh.ch)
  • We show that in the nephron BPGM is constitutively expressed, and up-regulated under conditions like acute kidney injury, clear cell renal carcinoma, or knock-out of the tumor suppressor von Hippel Lindau protein (VHL). (charite.de)
  • This gene encodes the protein elongin C, which is a subunit of the transcription factor B (SIII) complex. (avivasysbio.com)
  • Tuberous sclerosis complex is a dominantly inherited genetic disorder in which tumors (usually hamartomas) develop in multiple organs. (msdmanuals.com)
  • Ignesti, Marilena (2017) Uncovering the Relationship between Endocytosis and Awd, the Drosophila Homolog of Nme Metastasis Suppressor Proteins , [Dissertation thesis], Alma Mater Studiorum Università di Bologna. (unibo.it)
  • awd gene product is the ortholog of Nme1 and Nme2 (non-metastatic cell expression 1 and 2, respectively), which display metastasis suppressor abilities. (unibo.it)
  • Oncogenic protein tyrosine phosphatases have long been viewed as drug targets of interest, and recently developed allosteric inhibitors of SH2 domain-containing phosphatase-2 (SHP2) have entered clinical trials. (aacrjournals.org)
  • Sunitinib, sorafenib and pazopanib are small molecules that inhibit several protein kinases including tyrosine kinase of VEGF receptor. (czytelniamedyczna.pl)
  • Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice. (umassmed.edu)
  • This complex targets other proteins to be broken down (degraded) by the cell when they are no longer needed. (medlineplus.gov)
  • One of the targets of the VCB-CUL2 complex is a protein called hypoxia-inducible factor 2-alpha (HIF-2α). (medlineplus.gov)
  • The oxygen-sensitive sign event that regulates HIF is certainly mediated by hydroxylase enzymes that regulate the proteins balance and consequent transcriptional activity of HIF (20). (bioskinrevive.com)
  • The new results show that two different E3 enzymes, MDM2 and von Hippel-Lindau tumor suppressor (VHL), become immobilized in the structure and probably bind nucleolar scaffold proteins. (rupress.org)
  • VEGF protein is a potent proangiogenic factor that binds to its receptor on endothelial cells. (czytelniamedyczna.pl)
  • Bevacizumab is a monoclonal antibody that binds to a VEGF protein. (czytelniamedyczna.pl)
  • The change in electrostatic potential is likely to effect the binding of FLNA to the many proteins it interacts with. (wikipedia.org)
  • 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)
  • As has often been the case, hematologic malignancies have led the way in the introduction of this new generation of therapeutics-perhaps because of easy access to tumor samples for pharmacodynamics, and the narrow spectrum of cells of origin. (cancernetwork.com)
  • 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)
  • Tumour cells are good at adapting to their environment inside the organism and to variations in oxygen availability. (goethe-university-frankfurt.de)
  • Notably, surgical treatment has also the potential advantage of removing chemoradioresistant residual tumor foci, with a higher local control and possibly better survival, since resistance of cancer cells to CRT remains a major therapeutic drawback. (biomedcentral.com)
  • Type I tumors are more common and are composed of small cells characterized by their scanty basophilic cytoplasm and low nuclear grade. (renalandurologynews.com)
  • The VHL protein is found both in the nucleus and in the cytosol of transiently transfected cells. (nih.gov)
  • The foamy stromal cells between the capillaries stain positive for glial fibrillary acid protein and neuron-specific enolase. (medscape.com)
  • The haploinsuffcient dVHL (von-Hippel Lindau) gene is the Drosophila homolog of the human VHL tumour suppressor gene. (unibo.it)
  • Sema4D is regulated by HIF-1 and plays a role in tumor-associated macrophage-induced metastatic behavior and is clinically significant in colon cancer ( 9 ). (jcancer.org)
  • Further accumulation of genetic changes confers invasiveness or metastatic potential on the tumor ( 6 , 7 ), and to date, several indicators have been identified to predict outcomes ( 7 , 8 ). (iiarjournals.org)
  • Actin-binding protein, or filamin, is a 280-kD protein that crosslinks actin filaments into orthogonal networks in cortical cytoplasm and participates in the anchoring of membrane proteins for the actin cytoskeleton. (wikipedia.org)
  • The reasoning is that adrenal tumors might be responsible for many of the McCoys' notorious tempers. (the-scientist.com)
  • William Kaelin, Jr. was in 1995 engaged in the study of the von Hippel-Lindau tumor suppressor gene, and after isolation of the first full-length clone of the gene showed that it could suppress tumor growth in VHL mutant tumorigenic cell lines. (nobelprize.org)
  • Model-generated hypotheses were validated in multiple glioblastoma cell lines, in mouse tumor xenografts, and through analysis of The Cancer Genome Atlas data. (aacrjournals.org)
  • Furthermore, studies have shown HIF-mediated Sema4D induction in the generation of the pro-angiogenic phenotype in oral squamous cell carcinoma (OSCC) and have determined its biological significance for tumor growth and vascularity ( 10 ). (jcancer.org)
  • In the normal cell with active VHL protein, HIF alpha is regulated by hydroxylation in the presence of oxygen. (standardofcare.com)
  • A group of cell cycle proteins that negatively regulate the activity of CYCLIN / CYCLIN-DEPENDENT KINASE complexes. (nih.gov)
  • A family of cell cycle proteins containing ANKYRIN REPEATS that are specific inhibitors of cyclin D-dependent kinases. (nih.gov)
  • With this purpose, 84 genetically characterized tumors were analyzed by means of transcriptional profiling. (nih.gov)
  • Further, our study demonstrates that repression of key effector proteins in the post-transcriptional miRNA pathway impairs primary cilium formation. (biomedcentral.com)
  • 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)
  • methylation at certain residues of histones can regulate gene expression [ 4 ], and glycosylation is responsible for targeting substrates and changing protein half-life [ 2 ]. (hindawi.com)
  • A putative nuclear localization signal, a nuclear export signal, and a cytoplasmic retention locus have been identified in the VHL protein. (nih.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)
  • A crucial molecular event in molecular biology of renal cancer seems to be inactivation of von Hippel-Lindau ( VHL ) gene (3). (czytelniamedyczna.pl)
  • Protein expression is influenced by many factors that may vary between experiments or laboratories. (genscript.com)
  • This process wrongly signals that there is a shortage of blood vessels and activates the formation of blood vessels, driving tumor growth. (ascopost.com)
  • HIF is necessary for tumor growth. (standardofcare.com)
  • Transforming Growth Factor beta (TGF-β) is a signalling protein whose dysregulation can cause developmental disorders and cancer. (goethe-university-frankfurt.de)
  • However, not all are connected with the promotion of tumour growth, some being pro-apoptotic or growth inhibitory. (ox.ac.uk)
  • These proteins act as growth suppressors. (msdmanuals.com)
  • The analysis revealed a hypoxia-inducible factor (HIF)-related signature common to succinate dehydrogenase (SDH) and von Hippel-Lindau (VHL) tumors, that differentiated them from RET and neurofibromatosis type 1 cases. (nih.gov)
  • A VHL protein is mandatory for the process of hypoxia-inducible factor 1 (HIF-1) regulation (4). (czytelniamedyczna.pl)
  • 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)
  • and a second, previously identified and constitutively expressed and non-oxygen-regulated protein known as ARNT. (nobelprize.org)
  • The VHL tumor suppressor deactivates angiogenesis in an interesting oxygen sensing pathway. (the-scientist.com)