Role von hippel lindau tumor suppressor protein. Medical search. Frequent questions

Mutations of the VHL gene are associated with Von Hippel-Lindau disease, which is characterized by hemangioblastomas of the brain, spinal cord and retina. (wikipedia.org)
Nonsense or deletion mutations of VHL protein have been linked to type 1 VHL with a low risk of pheochromocytoma (adrenal gland tumors). (wikipedia.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)
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)
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 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)
VHL syndrome is distinct from most other autosomal dominant conditions because there should be two gene mutations present in order for tumors to begin forming, leading the presentation of the syndrome. (bajaprogofficial.com)
When there are two mutations in the VHL gene, abnormal proteins are produced and the function of the gene is altered. (bajaprogofficial.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)
Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with mutations, but not with WT mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring mutations. (bibf1120.com)
Moreover, we show that aminooxyacetate (AOA), a compound that inhibits enzymatic activity of aminotransferases, suppresses xenograft tumour growth of CRCs with mutations, but not with wild-type (WT) mutations and that targeting glutamine metabolism may be an effective approach to treating CRC patients harbouring tumour mutations of this gene. (bibf1120.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)
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)
The discovery of VHL mutations in a majority of localized as well as advanced renal carcinomas indicates that the VHL gene plays a critical role in the origin of both sporadic and hereditary kidney cancer. (grantome.com)
For instance, it can be activated by oncogenic mutations of PTEN, VHL, the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. (spandidos-publications.com)
A single normal cell randomly acquires a series of mutations that allows it to proliferate and to be transformed into a cancer cell (i.e., founding clone), which initiates tumor progression and recurrence. (nature.com)
We have previously shown that tumor founding clone mutations are able to predict tumor recurrence. (nature.com)
Acosta AM, Al-Obaidy KI, Sholl LM, Dickson BC, Lindeman NI, Hirsch MS, Collins K , Fletcher CD, Idrees MT. Sarcomatoid Yolk Sac Tumor Harbors Somatic Mutations That Are Otherwise Rare in Testicular Germ Cell Tumors. (iu.edu)

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)
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)
Solid tumors such as carcinomas of the lung, colon, breast, or prostate start in epithelial cells that line the surface of the bronchia, the intestinal mucosa, or the alveoli of fl uid secretion in the breast and prostate. (bbvaopenmind.com)
Different levels of viable cell inoculum density produced contrasting effects between 255 solid tumors as compared to 72 malignant. (shengsci.com)

The Von Hippel-Lindau tumor suppressor also known as pVHL is a protein that, in humans, is encoded by the VHL gene. (wikipedia.org)
Hydroxylation of HIF creates a binding site for pVHL (the protein product of the VHL gene). (wikipedia.org)
pVHL directs the polyubiquitylation of HIF1A, ensuring that this protein will be degraded by the proteasome. (wikipedia.org)
In types 1, 2A and 2B the mutant pVHL is defective in HIF regulation, while type 2C mutant are defective in protein kinase C regulation. (wikipedia.org)
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)
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)
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)
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)

This heterodimer of HIF is a transcription factor that activates genes that encode for proteins such as vascular endothelial growth factor (VEGF) and erythropoietin, proteins that are both involved in angiogenesis. (wikipedia.org)
The VHL protein likely plays a role in other cellular functions, including the regulation of other genes and control of cell division. (medlineplus.gov)
Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. (biomedcentral.com)
Hypoxia-inducible factor-1 (HIF-1) has a key role in cellular responses to hypoxia, including the regulation of genes involved in energy metabolism, angiogenesis and apoptosis. (ncl.ac.uk)
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)
There the SMAD proteins mediate the extent to which genes are activated and translated into proteins and other gene products. (goethe-university-frankfurt.de)
Through the analysis of hereditary kidney cancer syndromes, many important novel genes have been discovered such as the VHL gene responsible for Von Hippel-Lindau syndrome, and several previously known genes were re-discovered to have new essential functions including MET which is mutated in hereditary papillary renal cell carcinoma, and FH , the gene responsible for hereditary leiomyomatosis renal cell carcinoma. (kumamoto-u.ac.jp)
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)
To better understand the role of this and other putative pathways of gene regulation in VHL function we subjected mRNA from VHL defective renal carcinoma cells and transfectants re-expressing a wild type VHL allele to differential expression profiling, and analysed VHL target genes for oxygen regulated expression. (ox.ac.uk)
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)
Our results indicate that it will be necessary to consider the effects of abnormal activity in integral regulatory pathways, as well as the effects of individual genes to understand the role of abnormal patterns of gene expression in cancer. (ox.ac.uk)
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)
A program designed to identify tumor suppressor genes that are involved in the developoment and/or progression of prostate cancer is underway. (grantome.com)
Candidate cDNAs are being cloned from this region to be evaluated as potential tumor suppressor genes. (grantome.com)
The significance of this project lies in the identification of the tumor suppressor genes associated with kidney and prostate cancer as well as in the evaluation and development of new agents for use in therapy of patients with these neoplasms. (grantome.com)
The next most prevalent aberrations include a cohort of chromatin-modifying genes with diverse roles including PBRM1 , SETD2 , BAP1 , and KMD5C . (springer.com)
This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo‑I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). (spandidos-publications.com)
this association is primarily based on the HIF-1-mediated regulation of genes that play pivotal roles in the central features of cancer pathogenesis such as angiogenesis, invasion, metastasis and anti-apoptosis. (spandidos-publications.com)

This complex is involved in the ubiquitination and subsequent degradation of hypoxia-inducible factors (HIFs), which are transcription factors that play a central role regulating gene expression in response to changing oxygen levels. (wikipedia.org)
a protein component of a ubiquitin ligase complex) and hypoxia-inducible factors (a family of transcription factors activated by hypoxia). (lww.com)

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)

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)
The most relevant articles summarising existing knowledge on RCC genomics, including tumour cell evolution and progression, were selected for this review. (springer.com)
Hypoxia is an important micro-environmental factor in promoting tumor progression. (spandidos-publications.com)
Inflammation plays a role in the progression to cancer and it is linked to the presence of senescent cells. (shengsci.com)
We hypothesized that a preneoplastic field of inflammation, telomere shortening, and senescence underlies tumor progression in UC progressors. (shengsci.com)

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)
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)
They include tuberous sclerosis complex, Sturge-Weber syndrome , von Hippel-Lindau disease, and neurofibromatosis. (medscape.com)
Von Hippel-Lindau (VHL) Syndrome is an inherited disorder that is caused by a mutation in the VHL gene, which leads to an increased risk of development of tumors in the central nervous system (CNS) and viscera. (bajaprogofficial.com)
This means that one copy of the mutation, which may be inherited from either parent, is able to increase the risk of developing the tumors and VHL syndrome. (bajaprogofficial.com)
As a result of this, certain cells are able to divide more rapidly than usual and form tumors or cysts characteristic of VHL syndrome. (bajaprogofficial.com)
What is Von Hippel-Lindau Syndrome? (bajaprogofficial.com)
A novel tumor suppressor gene FLCN was identified in 2002 as the gene responsible for another hereditary kidney cancer syndrome, Birt-Hogg-Dubé syndrome. (kumamoto-u.ac.jp)
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 (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)

These often include hemangioblastomas, renal cell carcinoma (RCC) renal cysts and phaeochromocytoma, as well as tumors in the pancreas, epididymis uterus or endolymphatic sac in the inner ear. (bajaprogofficial.com)
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)
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)

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)
Semaphorin 4D (Sema4D) has been proven to be one of the hypoxia effectors regulated by hypoxia inducible factor (HIF-1) in multiple cells, and play a role in angiogenesis like VEGF. (jcancer.org)
In addition, these two binding sites play different roles in the regulation of Sema4D expression in HUVEC and Caco-2 cells. (jcancer.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)
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)
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)
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)
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)
Stimulus-secretion coupling in rat pituitary cells: role of cytosolic free [Ca++] in the stimulation of hormone secretion by thyrotropin-releasing hormone. (vdocuments.net)
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)
A further conversion of the malignant tumor leads to the formation of highly motile and invasive cancer cells, and the recruitment of normal cells that act as helpers in tumor dissemination. (bbvaopenmind.com)
Low ATP concentrations in hypoxic tumour cells disable the apoptotic cascade and induce cell death by necrosis. (bmj.com)
The VHL gene is a tumor suppressor gene located on chromosome 3 at 3p25-26 that is responsible for monitoring cell growth and division and preventing the cells from multiplying uncontrollably. (bajaprogofficial.com)
VEGF protein is a potent proangiogenic factor that binds to its receptor on endothelial cells. (czytelniamedyczna.pl)
Over the years, she has played a pivotal role in promoting the use of stem cells for the treatment of chronic degenerative conditions. (regenestem.com)
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)
In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
The increase of interleukin-4 (IL-4) level in tumor environment and the up-regulation of IL-4 receptor (IL-4R) on tumor cells have been long observed. (shengsci.com)

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 metabolic products of glutamine are utilized both to produce ATP and to synthesize macromolecules in the promotion of tumour growth4. (bibf1120.com)
However, not all are connected with the promotion of tumour growth, some being pro-apoptotic or growth inhibitory. (ox.ac.uk)

Invasion and metastasis are key features that distinguish malignant tumors-cancer proper-from benign growths. (bbvaopenmind.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)

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)
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)

The modified HIF-1α interacts with Von Hippel-Lindau (VHL), which is part of the E3 ubiquitin ligase complex targeting HIF-1α for 26S proteasomal degradation. (spandidos-publications.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)

Additionally, the nature of the mutation in the VHL protein leads to phenotypic manifestations in the pattern of cancer that develops. (wikipedia.org)
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 von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia. (ox.ac.uk)
The healthy gene itself may suppress the growth of tumors, resulting in uncontrolled cell growth when there is a mutation. (bajaprogofficial.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)

Although skeletal muscle is the major carnosine depot, the role of the dipeptide in preventing skeletal muscle injury has not been studied, and it is unclear whether carnosine affects ischemic damage or post injury events underlying wound healing and tissue angiogenesis. (frontiersin.org)

This group of proteins ubiquitinates substrates in the body and marks them for degradation when they're not needed. (bajaprogofficial.com)

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)
We have identified the tumor suppressor gene for the familial form of kidney cancer associated with von Hippel Lindau disease and have shown that the VHL gene is the kidney cancer tumor suppressor gene. (grantome.com)

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)

An intracellular signaling and tumor suppressor protein that forms a complex with TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN (TSC1) and other signaling factors to negatively regulate MTORC1 and affect cell growth and proliferation. (bvsalud.org)

The main action of the VHL protein is thought to be its E3 ubiquitin ligase activity that results in specific target proteins being 'marked' for degradation. (wikipedia.org)
One of the key target proteins is hypoxia-inducible factor 2-alpha (HIF-2α), which plays a significant role in another protein complex referred to as HIF that affects the ability of an individual to adapt to atmospheric oxygen changes. (bajaprogofficial.com)

Apoptosis regulatory proteins are delicately balanced. (bmj.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)
Endogenous interleukin-4 promotes tumor development by increasing tumor cell resistance to apoptosis. (shengsci.com)

Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)

Von Hippel-Lindau disease can be split into two subtypes, Type 1 and Type 2, depending on the presence of pheochromocytomas [5] . (eyewiki.org)
Type 1 VHL has a low risk of pheochromocytomas, but both subtypes present with multiple organ tumors [5] . (eyewiki.org)

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)
Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)

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)
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)
Understanding the proteins that regulate the 5-HT1A promoter will lead to insights on receptor regulation and provide new therapeutic targets relevant to depression, anxiety, obsessive compulsive disorder and other mental illnesses. (vdocuments.net)
The von Hippel-Lindau tumour suppressor gene (VHL) targets hypoxia inducible factor (HIF)-alpha subunits for ubiquitin dependent proteolysis. (ox.ac.uk)
In characterizing the biochemical function of the VHL gene we have recently shown that the B and C regulatory subunits of the cellular transcription factor Elongin (SIII) are targets of the VHL protein. (grantome.com)

Among these transcription factors, hypoxia-inducible factor-1 (HIF-1) is one of the most important factors that play a critical role in controlling oxygen delivery and metabolic adaptation to hypoxic conditions. (spandidos-publications.com)

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)
Bevacizumab is a monoclonal antibody that binds to a VEGF protein. (czytelniamedyczna.pl)
Sunitinib, sorafenib and pazopanib are small molecules that inhibit several protein kinases including tyrosine kinase of VEGF receptor. (czytelniamedyczna.pl)
We have identified the localization signals for the VHL protein to move to the nucleus and for retention in the nucleus and shown that the VHL protein regulates VEGF expression in post-transcriptional manner. (grantome.com)

Phosphorylation of the Mdm2 oncoprotein by the c-Abl tyrosine kinase regulates p53 tumor suppression and the radiosensitivity of mice. (umassmed.edu)

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)
There are several functions of the VHL gene within the body, one of which is to regulate the production of proteins in the VCB-CUL2 complex. (bajaprogofficial.com)
These nutrient-driven post-translational modifications are highly altered in cancer and regulate protein functions in various cancer-associated processes. (biomedcentral.com)

In the normal cell with active VHL protein, HIF alpha is regulated by hydroxylation in the presence of oxygen. (wikipedia.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)
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)
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)
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)
This occurs due to changes in the production of proteins in the body, which are involved in the regulation of cell growth and division. (bajaprogofficial.com)
In particular, the proteins in the VCB-CUL2 complex change and affect the regulation of cell growth in the body. (bajaprogofficial.com)
A recent study showed that loss of tumour suppressor von hippel-lindau tumor suppressor (VHL) renders renal cell carcinomas sensitive to glutamine deprivation through hypoxia induced factor (HIF)-induced metabolic reprogramming10. (bibf1120.com)
encodes the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), which plays a key role in regulating cell proliferation, survival and motility12. (bibf1120.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 Von Hippel-Lindau ( VHL ) tumour suppressor gene undergoes bi-allelic knockout in the vast majority of clear cell RCCs. (springer.com)
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)
Effects of tumor cell viability and inoculum density on growth parameters in the human tumor, soft-agar clonogenic assay. (shengsci.com)
Collins K , Segura S, Hwang M. Endocrine cell micronests in an ovarian mucinous borderline tumor: a potential diagnostic pitfall for microinvasion. (iu.edu)
The purpose of this study was to investigate the role and mechanism of hypoxia-induced renal cell carcinoma and provide evidence-based medical proof for improvements to postoperative nursing of renal cell carcinoma patients. (biomedcentral.com)
Nursing based on oxygen administration decreased the value of renal function indexes, serum inflammatory factors, and tumor markers in renal cell carcinoma patients. (biomedcentral.com)

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)
Hence, pre-existing germline variants provide a profound constraint on the evolution of tumor founding clones and subclones and therefore have a contingent effect on the genetic makeup of tumor and presumably patient outcomes. (nature.com)

Fundamental role for the creatine kinase pathway in protection from murine colitis. (ucdenver.edu)

Renal function indexes, serum inflammatory factors, and tumor markers were evaluated. (biomedcentral.com)

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)
Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC. (shengsci.com)

The VHL gene provides instructions for making a protein that functions as part of a complex (a group of proteins that work together) called the VCB-CUL2 complex. (medlineplus.gov)

this feature makes it difficult to identify dysplastic lesions when the tumor elevation and size is not large. (iiarjournals.org)

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)
Tumors involving other organs and the CNS (brain, spinal cord) are present in 25% of patients with VHL disease. (medscape.com)
Cancer patients and tumor-bearing animals excrete high levels of modified purines and pyrimidines some of which, e.g. (shengsci.com)
Germline variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. (nature.com)
Most patients carry a missing or damaged p53 gene, a tumor suppressor whose activity is impaired in almost 50% of all cancers. (nature.com)

HIFs are necessary for tumor growth because most cancers demand high metabolic activity and are only supplied by structurally or functionally inadequate vasculature. (wikipedia.org)
Transforming Growth Factor beta (TGF-β) is a signalling protein whose dysregulation can cause developmental disorders and cancer. (goethe-university-frankfurt.de)
This process wrongly signals that there is a shortage of blood vessels and activates the formation of blood vessels, driving tumor growth. (ascopost.com)
On growth factor stimulation, p85 is recruited to phosphorylated receptor protein kinases and adaptor proteins, thereby activating PI3K. (bibf1120.com)
Here, we found that endogenous IL-4 promotes tumor growth because neutralizing IL-4 by 11B1. (shengsci.com)

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)
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)
A crucial molecular event in molecular biology of renal cancer seems to be inactivation of von Hippel-Lindau ( VHL ) gene (3). (czytelniamedyczna.pl)
In collaboration with radiologists at Stanford, we are working to define the optimal role of MRI in prostate cancer. (stanford.edu)
Background: ZNRD1-AS1 plays an important role in liver cancer, endometrial cancer and other diseases. (worldcarecouncil.org)

Our findings identify a novel role for VHL in mediating nephron progenitor differentiation through metabolic regulation, and suggest that VHL is required for normal kidney development. (lww.com)
Allostery is one of the most powerful and common ways of regulation of protein activity. (biomedcentral.com)
Tight regulation of these processes is fundamental in all kingdoms of life and allostery represents one of the most commmon and powerful means of modulating protein activity[ 1 ]. (biomedcentral.com)
A VHL protein is mandatory for the process of hypoxia-inducible factor 1 (HIF-1) regulation (4). (czytelniamedyczna.pl)

However, their significance for tumor development has not been investigated. (shengsci.com)

A region from the short arm of chromosome 8 (8p22) has been shown to be lost frequently in prostate tumors as well as prostate intraepithelial neoplasia (PIN). (grantome.com)

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 mechanisms under-lying oxygen sensing in animals have been previously marked by two Nobel Prizes from more than 75 years ago: to Otto Warburg in 1931 for his discoveries concerning the enzymatic basis for cellular respiration, and to Corneille Heymans in 1938 for his findings on the role of the nervous system in the respiratory response to oxygen. (nobelprize.org)
Protein posttranslational modifications (PTMs) play key roles in a variety of protein activities and cellular processes. (hindawi.com)
PTMs are involved in many protein activities and cellular processes, such as protein folding, stability, conformation, and some significant regulatory mechanisms [ 1 ]. (hindawi.com)

Further, our study demonstrates that repression of key effector proteins in the post-transcriptional miRNA pathway impairs primary cilium formation. (biomedcentral.com)

HIF1α and HIF2α play crucial roles in VHL disease, particularly with respect to ccRCC and hemangioblastoma. (biomedcentral.com)

Pre-treatment tumor tissue biopsies were obtained during staging procedures, the joint assessment by surgeon and pathologist allowing an unequivocal identification of tumor area to be sampled. (biomedcentral.com)
Identification of the von Hippel-Lindau disease tumor suppressor gene. (abvpress.ru)

However protein activities are closer to disease activities. (hindawi.com)
Von Hippel-Lindau disease manifests in the third to fourth decades of life, depending on the location of the tumors. (eyewiki.org)
Definitive diagnosis of Von Hippel-Lindau disease occurs in one of two ways. (eyewiki.org)

With this purpose, 84 genetically characterized tumors were analyzed by means of transcriptional profiling. (nih.gov)
In contrast, SLC1A5 expression is repressed by the Rb tumour suppressor7, whereas GLS2 was identified as a transcriptional target of p53 (ref. 8). (bibf1120.com)
These findings reveal an important transcriptional regulatory network and suggest that the VHL protein may function as a key regulator of this network, with its ultimate target the RNA polymerase II elongation complex. (grantome.com)

Anatomy7

Diseases8

Chemicals and Drugs42

Analytical, Diagnostic and Therapeutic Techniques and Equipment4

Phenomena and Processes30

Humanities1

Information Science3

Mutations29

Solid tumors6

PVHL14

Genes21

Hypoxia-inducib2

Renal carcinoma1

Progression5

Syndrome10

Endolymphatic sac3

Cells22

Nuclear and cytoplasmic1

Promotion of tumour2

Benign2

Retinal3

Interacts1

Amino acids1

Mutation7

Angiogenesis1

Ubiquitinates1

Familial3

Ubiquitin ligase complex1

Tuberous scleros1

Target proteins2

Apoptosis3

Degradation1

Pheochromocytomas2

Pathways2

Targets6

Hypoxic1

VEGF4

Tyrosine1

Regulate3

Cell17

Genetic2

Kinase1

Factors1

Mechanism2

Group of proteins1

Lesions1

Patients5

Growth5

Cancer5

Regulation4

Significance1

Chromosome1

Overexpression1

Cellular3

Post-transcriptional1

CcRCC1

Identification2

Disease3

Transcriptional3