• 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)
  • The haploinsuffcient dVHL (von-Hippel Lindau) gene is the Drosophila homolog of the human VHL tumour suppressor gene. (unibo.it)
  • 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)
  • We observed gain of functions in VHL mutations, thereby stabilizing HIF2α protein and reprograming HIF2α genome-wide target gene transcriptional programs. (biomedcentral.com)
  • 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)
  • 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)
  • 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)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (ayassbioscience.com)
  • This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. (ayassbioscience.com)
  • In this report, we describe a testis zinc finger protein (Tzfp) that binds to the upstream flanking sequence of the Aie1 gene. (lookformedical.com)
  • The mouse Tzfp gene, mapped to chromosome 7 B2-B3, encodes a 465-amino acid transcription factor containing a conserved N-terminal BTB/POZ domain and three C-terminal PLZF-like C(2)H(2) zinc fingers. (lookformedical.com)
  • Renal cell carcinoma (RCC) is the most common malignant kidney tumor and has a high incidence rate. (biomedcentral.com)
  • Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION. (lookformedical.com)
  • Homologues are known to exist between human VBP-1 and proteins in mice, Drosophila and C. elegans. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • To evaluate the capacity of the UPS to degrade disease related proteins, polyglutamine (polyGln) proteins were targeted for proteasomal degradation. (5dok.org)
  • However, aggregation of the aggregation- prone polyGln proteins prevented proteasomal degradation. (5dok.org)
  • 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)
  • A mutant form of Ub, UBB +1 is another protein that can resist proteasomal degradation. (5dok.org)
  • Since the UPS is also responsible for the degradation of ER proteins we investigated the effect of ER stress on the functionality of the UPS. (5dok.org)
  • However, in these diseases the UPS is compromised and some proteins might resist degradation. (5dok.org)
  • degradation of polyglutamine proteins. (5dok.org)
  • When oxygen is plentiful, HIF-1 is ubiquitinated and targeted for degradation by the von Hippel Lindau protein (VHL-1), which inactivates HIF-1. (uw.edu)
  • 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)
  • Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.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)
  • Prefoldin subunit 3 (VBP-1), also Von Hippel-Lindau binding protein 1, is a prefoldin chaperone protein that binds to von Hippel-Lindau protein and transports it from perinuclear granules to the nucleus or cytoplasm inside the cell. (wikipedia.org)
  • 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)
  • 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)
  • VEGF-induced pMF was attenuated by the MEK/ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis( o -aminophenylmercapto)butadiene] and was abolished by the phosphotidinositol 3 kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4 H )-benzopyran-4-one hydrochloride], demonstrating that ERK mitogen-activated protein kinases and Akt are both required for full expression of VEGF-induced pMF. (jneurosci.org)
  • 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)
  • 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)
  • An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
  • The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.com)
  • In fact, HIF-1α is a major factor for regulating tumor microenvironment (TME) for tumor cell survival and angiogenesis [6, 7]. (cd4inhibitors.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)
  • This is contrary to humans, where VHL-1 mutations cause a disease characterized by angiomas, renal carcinomas and various other tumors as a direct result of aberrant HIF-1 activation. (uw.edu)
  • 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)
  • At least one of these genes, flavin-monooxygenase-2, is a well-conserved protein known to be involved in xenobiotic metabolism. (uw.edu)
  • Hypoxia is an important micro-environmental factor in promoting tumor progression. (spandidos-publications.com)
  • Therefore, inhibition of HIFs protein expression may be an attractive way to prevent tumor progression [6]. (cd4inhibitors.com)
  • This inhibition reduces tumor vascularization, and leads to tumor shrinkage. (biomedcentral.com)
  • The presence of Remodelin could suppress the elevated level of HIF-1α protein and its nuclear translocation induced by either treatment of cobalt chloride (CoCl2) or hypoxia in dose or time-dependent way. (cd4inhibitors.com)
  • The ubiquitin-proteasome system (UPS) is the main pathway in the cell for the elimination of aberrant or misfolded proteins. (5dok.org)
  • A common feature in many of these diseases is the presence of aggregated proteins that are covalently linked to ubiquitin (Ub). (5dok.org)
  • and a second, previously identified and constitutively expressed and non-oxygen-regulated protein known as ARNT. (nobelprize.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)
  • These nutrient-driven post-translational modifications are highly altered in cancer and regulate protein functions in various cancer-associated processes. (biomedcentral.com)
  • N signalling is a highly conserved cell-cell communication pathway that mediates critical cell fate decision events occurring both in insects and vertebrates. (unibo.it)
  • 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)
  • 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 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)
  • They are highly stable and have organ- and tissue-specific expression patterns. (biomedcentral.com)
  • Under well-oxygenated conditions, HIFs rapidly degraded by hydroxylation and bound to the von Hippel-Lindau (VHL) protein, while the hydroxylation of HIFs was inhibited and resulted in its highly expression in hypoxic conditions [3, 4]. (cd4inhibitors.com)
  • The expression of HIFs protein should be inhibited because it is great essential for tumor growth. (cd4inhibitors.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)
  • 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)
  • Nme1 is found in human body fluids and its protein level correlates with prognosis in cancer patients. (unibo.it)
  • To explain this briefly, if the pathogen's active site is very well conserved in nature it may share important structural features with the human homologue, which could be then bound and inhibited as well by the antimicrobial drug causing toxic side-effects on the patient. (biomedcentral.com)
  • Her research has redefined the molecular map of breast cancer and led to new paradigms in understanding how human tumors evolve and metastasize. (stanford.edu)
  • N-acetyltransferase 10 (NAT10, or hALP, human N-acetyltransferase-like protein) is a nucleolar protein with lysine acetylation activity, which embraces GNAT, RNA helicase and tRNA-binding domain [8]. (cd4inhibitors.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 family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
  • CircRNAs have essential functions as microRNA sponges, RNA-binding protein- and transcriptional regulators, and protein translation templates. (biomedcentral.com)
  • Nevertheless, in neurodegenerative diseases these proteins accumulate with disastrous consequences for neurons, eventually leading to cell death. (5dok.org)
  • Furthermore, we implemented an approach that achieves 65% positive predictive value in identifying allosteric sites within the set of predicted cavities of a protein (stricter parameters set, 0.22 sensitivity), by combining the current analysis on dynamics with previous results on structural conservation of allosteric sites. (biomedcentral.com)
  • Proteins can be regarded as the functional building blocks of life, carrying out and coordinating almost all biological processes. (biomedcentral.com)
  • Gain of function of a metalloproteinase associated with multiple myeloma, bicuspid aortic valve, and Von Hippel-Lindau syndrome. (salvesenlab.org)
  • Aurora kinases are found in all organisms in which their function has been conserved throughout evolution, namely the control of chromosome segregation. (lookformedical.com)
  • have determined that Remodelin can inhibit the function of the acetyltransferase protein NAT10 and reduce cancer cell migration and invasion [13-15]. (cd4inhibitors.com)
  • The distribution of NAT10 and its role in cell divi- sion raised the possibility that this protein play an important role in the proliferation of cancer cells [10]. (cd4inhibitors.com)
  • For example, allosteric sites tend to be under lower sequence-conservation pressure than active sites, facilitating the design of highly specific drugs and reducing the risks of toxicity or side-effects[ 5 - 7 ]. (biomedcentral.com)
  • The cover for issue 34 of Oncotarget features Figure 2, "Potential paradigm-shifting effect of a cancer stem cell (CSC) inhibitor on tumor chemoresistance," from Oronsky, et al . (oncotarget.com)
  • In this article, we describe a simple computational approach, based on the effect allosteric ligands exert on protein flexibility upon binding, to predict the existence and position of allosteric sites on a given protein structure. (biomedcentral.com)
  • However, for most allosteric proteins identified to date the mechanistic details of allosteric modulation are not yet well understood. (biomedcentral.com)
  • Ser65 residue, located within the β-domain and nearby the interaction sites with hypoxia-inducing factor α (HIFα), is highly conserved among different species. (biomedcentral.com)
  • We introduce a simple computational approach to predict the presence and position of allosteric sites in a protein based on the analysis of changes in protein normal modes upon the binding of a coarse-grained ligand at predicted cavities. (biomedcentral.com)
  • We performed normal-mode analysis and observed significant changes in protein flexibility upon allosteric-ligand binding in 70% of the cases. (biomedcentral.com)