• Tuberous sclerosis is an autosomal dominant disease in which the genes required to express the tumor-suppressant proteins that form the TSC complex is mutated or missing, so the TSC complex is unable to function properly. (wikipedia.org)
  • UPTON, NY-Scientists have captured atomic level snapshots showing how one key enzyme modifies a protein involved in turning genes on or off inside cells. (bnl.gov)
  • The human genome contains about 20,000 protein-coding genes -- less than 2 percent of the total -- but 70 percent of the genome is made into non-gene-encoding RNA. (sciencedaily.com)
  • Genomic studies of TNBC to crack its tough-to-treat status have mainly focused on protein-coding genes and the function of non-coding genes is still largely unknown. (sciencedaily.com)
  • Nowell, a tumor biologist in the pathology department at the University of Pennsylvania School of Medicine, was interested in the relationship between cancer and alterations in genes (although he had no proof there was one). (laskerfoundation.org)
  • The elevated HIF-1α accumulates and makes a translocation to the nucleus, regulating the expression of target genes in the nucleus, which regulate a variety of cellular processes to promote survival. (cd4inhibitors.com)
  • We then studied the mutated gene functions to evaluate causal links to cancer, such as for genes that encoded known tumor suppressor proteins. (emerginginvestigators.org)
  • Notably, this study has potential wider significance because the seven genes targeted by recurrent mutations are also involved in other cancers. (emerginginvestigators.org)
  • In the presence of Wnt signals, the Wnt proteins bind to (frizzled) frizzled receptors ( FZDs ) and low-density lipoprotein receptor-related protein ( LRP ) receptors, leading to the stabilization of β-catenin , its transfer to the nucleus, and the activation of target genes. (hindawi.com)
  • β-catenin forms a complex with T-cell factor ( TCF ) /lymphoid enhancer factor ( LEF ) transcription factors and cofactors such as histone acetyltransferase p300 (p300), CBP, BCL9, and pygopus, to transcribe Wnt signaling target genes such as Cyclin D1 , C-Myc , and survivin [ 9 , 12 - 15 ]. (hindawi.com)
  • Researchers have mapped mutational signatures in each of the 29 genes that make up the mSWI/SNF complex, with a view to predicting the tumours that may best respond to targeted treatment ( Molecular Cell ). (frontlinegenomics.com)
  • Both genes are tumor suppressors, meaning they normally help keep the body cancer-free. (medicalxpress.com)
  • p53 is one of the most important tumor suppressor genes, and more than half of cancer patients carry mutations in the p53 gene. (medicaltrend.org)
  • What is interesting is that although these mice showed activation of p53 (for example, the up-regulation of p53 target genes was observed in different tissues), the content of p53 protein did not increase significantly. (medicaltrend.org)
  • Transcriptional activity is regulated by DNA binding transcription factors, but these typically act in more than one cell lineage activating different subsets of target genes in each. (edu.au)
  • Random set analysis was used to identify biological pathways enriched for genes differentially regulated in tumors (compared with 59 samples of normal mucosa). (biomedcentral.com)
  • This week in Nature Genetics , two studies report recurrent mutations in splicing-related genes in blood tumors. (massgenomics.org)
  • Chromosome 1 likely contains 2,000 to 2,100 genes that provide instructions for making proteins. (medlineplus.gov)
  • When tumor suppressor genes are deleted, cancer can occur. (medlineplus.gov)
  • Researchers have identified several possible tumor suppressor genes in the deleted region of chromosome 1, and more research is needed to understand what role these genes play in neuroblastoma development. (medlineplus.gov)
  • SNPs in 6 miRNA processing genes and in 78 miRNAs which target genes known to be important in breast cancer among 906 African American (AA) and 653 European American (EA) cases and Author Manuscript controls enrolled in the Women's Circle of Health Study (WCHS). (cdc.gov)
  • Thus, the function of miRNA may ultimately depend on the specific microenvironment of a particular cell type, which can provide different repertoire of target genes. (bvsalud.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)
  • Here we demonstrate a critical role for the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL in HIF-1 regulation. (ncl.ac.uk)
  • 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)
  • 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)
  • 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)
  • Another paper in the journal Nature Communications reported SP141's ability to degrade MDM2 and delay breast cancer progression and reduce its metastasis. (rosalindfranklin.edu)
  • Therefore, inhibition of HIFs protein expression may be an attractive way to prevent tumor progression [6]. (cd4inhibitors.com)
  • Although PDCD4 in general suppresses the development and progression of tumors, its specific biological functions differ by cell type [8] . (plos.org)
  • Autophagy, an evolutionarily conserved catabolic process, has a crucial role in tumor initiation and progression. (spandidos-publications.com)
  • Tumour cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. (researchgate.net)
  • Recent study at IMBB, published in Cell Death and Disease revealed that CISD-1, an iron sulfur cluster binding protein implicated in the pathogenesis of the neurodegenerative disorder Wolfram Syndrome type 2, modulates longevity and proteostasis by engaging autophagy and the mitochondrial intrinsic apoptosis pathway. (forth.gr)
  • p53 can activate a variety of signaling pathways to inhibit tumors, such as cell cycle arrest, cell senescence, apoptosis or iron death. (medicaltrend.org)
  • Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) modulates cellular apoptosis, which is involved in the occurrence and development of liver cancer. (spandidos-publications.com)
  • In addition, Beclin 1 gene deletion results in tumor cell apoptosis, specifically in hypoxic regions ( 12 ). (spandidos-publications.com)
  • The NHEJ pathway, which repairs double-strand breaks in DNA, is one of the major pathways in tumor cells that respond to radiation treatment and chemotherapeutic agents. (sciencedaily.com)
  • The two most important molecular targets for new drugs in renal cancer are vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. (czytelniamedyczna.pl)
  • He works to identify novel drug targets and discover compounds that can weaponize the body against an enemy that uses its host's own cells, pathways and viral vectors to survive, multiply and kill. (rosalindfranklin.edu)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • The kinases IKBKE and TBK1 regulate MYC-dependent survival pathways through YB-1 in AML and are targets for therapy. (broadinstitute.org)
  • R-Ras proteins function distinctly from classic Ras proteins by regulating distinct signaling pathways that promote MPNST tumorigenesis by mediating migration and invasion. (biomedcentral.com)
  • We have previously shown that three related Ras proteins (the classic Ras proteins) are highly activated in malignant peripheral nerve sheath tumor (MPNST) cells with neurofibromin loss and that they drive cancer cell proliferation and survival by activating multiple cellular signaling pathways. (biomedcentral.com)
  • We examined the activation of cytoplasmic signaling pathways in the presence and absence of R-Ras signaling and found that R-Ras proteins regulated 13 signaling pathways distinct from those regulated by classic Ras proteins. (biomedcentral.com)
  • Of the 880 canonical pathways we investigated, 112 displayed significant tumor-related upregulation or downregulation at one or more stages of tumorigenesis. (biomedcentral.com)
  • S transition in the cell cycle, upregulated expression of tumor-promoting microenvironmental factors, and profound dysregulation of metabolic pathways (e.g., increased aerobic glycolysis, downregulation of pathways that metabolize drugs and xenobiotics). (biomedcentral.com)
  • The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1) 1 , 2 . (nature.com)
  • Somatic Nf1 mutations are also present in 5-10% of cancers, demonstrating the role of Nf1 as a tumour suppressor 1 . (nature.com)
  • With inherited diseases such as cystic fibrosis, mutations in the CFTR gene produce a protein that remains functional but is subject to excessive ubiquitination, leading to its rapid degradation via the proteasome. (businesswire.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)
  • We observed gain of functions in VHL mutations, thereby stabilizing HIF2α protein and reprograming HIF2α genome-wide target gene transcriptional programs. (biomedcentral.com)
  • Cancer-associated protein kinase C mutations reveal kinase's role as tumor suppressor. (tang-prize.org)
  • Men with FOXA1 mutations in their tumor have a worse prognosis than men without these mutations. (mskcc.org)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • There is a highly sophisticated way to treat some breast and ovarian cancers-a class of drugs called PARP inhibitors, designed to exploit the very defects that make tumors with certain mutations especially deadly. (medicalxpress.com)
  • Mutations of the NF1 gene potentially results in the activation of multiple Ras proteins, which are key regulators of many biologic effects. (biomedcentral.com)
  • Sub-gene algorithms provide a high-resolution view that can explain why different mutations in the same gene can lead to distinct phenotypes, depending on how the mutation impacts specific protein regions. (bsc.es)
  • Mutations in certain regions of NOTCH1 cause it to act as a tumor suppressor in lung, skin and head and neck cancers. (bsc.es)
  • Specifically, the TSC2 subunit, tuberin of the complex interacts with and inhibits RHEB to regulate the protein. (wikipedia.org)
  • AIM2 is a strong candidate as a tumor suppressor as it is a member of the HIN-200 (hemopoietic interferon-inducible, nuclear proteins containing a 200 amino acid repeat) family of proteins that have been shown to regulate cell growth and survival. (enzolifesciences.com)
  • Dr. Buolamwini, professor and chair of pharmaceutical sciences in the College of Pharmacy, worked with an interdisciplinary team of scientists in discovering a new class of small molecule inhibitors of the rogue, cancer-causing protein MDM2, which opposes the effects of the famous tumor suppressor p53, a gene that is thought to regulate the cell cycle and stop damaged cells from dividing. (rosalindfranklin.edu)
  • STAT proteins - especially STAT3 and STAT5 - regulate all of these processes and are persistently activated in a surprisingly large number of human cancers. (researchgate.net)
  • This is mainly because there are many proteins that regulate p53 levels in cells, the most important of which is MDM2. (medicaltrend.org)
  • Inhibition of R-Ras/R-Ras2 and ROCK1 signaling also triggered the accumulation of abnormal intracellular vesicles, indicating that these signaling molecules regulate the movement of proteins and other molecules in the cellular interior. (biomedcentral.com)
  • Recent studies have found that post-translational modifications of proteins can regulate the occurrence and development of tumors. (cmbr-journal.com)
  • MicroRNAs (miRNA) are small noncoding RNAs, preserved throughout the evolution, able to regulate gene expression through repression of translation or degradation of target molecules of messenger RNA. (bvsalud.org)
  • For this reason, ways to inhibit RHEB to control the mTOR pathway are studied as possible treatments for uncontrollable tumor cell growth in several diseases, especially in tuberous sclerosis. (wikipedia.org)
  • 2. Zhang, Y. et al: Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. (signalchem.com)
  • Programmed cell death 4 (PDCD4) is an important tumor suppressor in the development of various human cancers [1] and inhibits translation rather than transcription. (plos.org)
  • The transition between closed, self-inhibited states of Nf1 and open states provides guidance for targeted studies deciphering the complex molecular mechanism behind the widespread neurofibromatosis syndrome and Nf1 dysfunction in carcinogenesis. (nature.com)
  • They published their findings this week in Nature Structural & Molecular Biology . (sciencedaily.com)
  • In recent years, the advances in molecular biology of renal cancer and development of targeted agents have expanded the therapeutic armamentarium. (czytelniamedyczna.pl)
  • Researchers at Memorial Sloan Kettering have identified molecular changes in a protein that promote a distinct type of prostate cancer. (mskcc.org)
  • Yu, H. & Jove, R. The STATs of cancer - new molecular targets come of age. (researchgate.net)
  • We used a molecular pathway-based approach to analyze transcriptomic profiles of 59 colorectal tumors representing early and late preinvasive stages and the invasive stage of tumorigenesis. (biomedcentral.com)
  • Using a clinically guided genetic screening approach, researchers identified a non-coding RNA that is overexpressed in triple-negative breast cancer cells and regulated by the tumor suppressor p53 and the activated cell surface protein, EGFR. (sciencedaily.com)
  • This lncRNA is overexpressed in triple-negative breast cancer cells and regulated by the tumor suppressor p53 and the activated cell surface protein, EGFR. (sciencedaily.com)
  • Since hormones are not supporting growth, the cancer is unlikely to respond to hormonal therapies and medications that target HER2. (sciencedaily.com)
  • Given the important role of LINP1 in the NHEJ pathway, our study indicates that this new class of cancer-driver gene -- the lncRNAs -- may serve as unique therapeutic targets and novel biomarkers in cancer," Zhang said. (sciencedaily.com)
  • Excess ubiquitination is also a feature of cancer, where E3 ubiquitin ligases - enzymes that add ubiquitin to proteins - are frequently upregulated or amplified, driving the degradation of tumor suppressor proteins. (businesswire.com)
  • Protein kinase C in cancer: The top five unanswered questions. (tang-prize.org)
  • SP141, as reported in the journal Gastroenterology in 2014, reduced levels of MDM2 in pancreatic cancer cell lines and inhibited the growth of pancreatic tumors in mice. (rosalindfranklin.edu)
  • MSK cancer researchers Elizabeth Adams, Charles Sawyers, and Rohit Bose are studying the underlying biology of prostate cancer tumors in order to develop better treatments. (mskcc.org)
  • HIFs have been considered a therapeutic target for cancer and development of their inhibitor has been extensively explored. (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)
  • have determined that Remodelin can inhibit the function of the acetyltransferase protein NAT10 and reduce cancer cell migration and invasion [13-15]. (cd4inhibitors.com)
  • Therapeutically targeting tumor microenvironment-mediated drug resistance in estrogen receptor-positive breast cancer. (broadinstitute.org)
  • A specialised diet could trigger ferroptosis - a type of programmed cell death - in glioblastoma cells, making the cancer more sensitive to certain treatments ( Nature Communications ). (frontlinegenomics.com)
  • Yet this targeted approach to cancer therapy sometimes fails, and scientists have anxiously sought to understand why. (medicalxpress.com)
  • But it wasn't clear why losing this protein gives these cancer cells such a deadly advantage. (medicalxpress.com)
  • Consequently, STAT proteins are emerging - unexpectedly - as ideal targets for cancer therapy. (researchgate.net)
  • They found that PML limits breast cancer metastasis by inhibiting cancer stem cell survival, tumor cell migration and blood vessel formation. (forth.gr)
  • Swedish Research Counsil (R.J.A.N.), National Cancer Institute (NCI) CA069246 and CA86355 (X.O.B.), and the American Brain Tumor Association (T.W.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. (plos.org)
  • VEGF, produced in large amounts by cancer cells during tumor growth, interacts with its receptors VEGFR1 and VEGFR2 thereby causing endothelial cell survival, proliferation, and sprouting [7] . (plos.org)
  • loss of neurofibromin could cause these Ras proteins to become persistently active, leading to the development of cancer. (biomedcentral.com)
  • Zhang S-W, Wang H, Ding X-H, Xiao Y-L, Shao Z-M, You C, Gu Y-J, Jiang Y-Z (2022) Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment: Beyond tumor antigens. (cmbr-journal.com)
  • The study researchers applied each sub-gene algorithm to the data from The Cancer Genome Atlas (TCGA), a large-scale data set that includes genome data from 33 different tumor types from more than 11,000 patients. (bsc.es)
  • This study should help researchers understand the advantages and drawbacks of sub-gene algorithms used to find new potential drug targets for cancer treatment. (bsc.es)
  • Figure: Three cancer mutation groups in the protein PIK3CA identified by different subgene algorhytms. (bsc.es)
  • His research utilizes the tools of synthetic chemistry, protein biochemistry, and cancer biology to discover and validate new strategies for the inhibition of anti-cancer targets. (stanford.edu)
  • Common among these 10 interactions of organic compounds, their power to detect excess cancer agents is the electrophilic nature of or their metabolites, with DNA and R 1 risk at particular sites. (who.int)
  • 2021 Nature Microbiology 6:455. (ccf.org)
  • p38γ and δ promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation. (nature.com)
  • Protein stabilization can be thought of as the inverse of protein degradation. (businesswire.com)
  • However, because proteasome inhibitors globally inhibit protein degradation in a non-specific manner, their use outside of oncology is limited by poor tolerability, highlighting the need for targeted approaches. (businesswire.com)
  • Activation of p53 by DNA strand breaks is orchestrated by the ataxia-telangiectasia mutated (ATM) protein kinase and involves interruption of Hdm2-mediated p53 degradation. (dundee.ac.uk)
  • Pin1 down-regulates transforming growth factor-beta (TGF-beta) signaling by inducing degradation of Smad proteins. (idrblab.net)
  • Similarly, for p53 to function as a tumor suppressor gene, it also needs to get rid of MDM2-mediated degradation, so as to stabilize the p53 protein to function. (medicaltrend.org)
  • Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (intechopen.com)
  • Recent studies, including publications from the Penn group, have identified lncRNAs with tumor suppressive and oncogenic activities in cancers. (sciencedaily.com)
  • Depending on the context and the cell is type they are expressed, one can view miRNA oncogenic or tumor suppressor activity. (bvsalud.org)
  • The research, published in Nature Chemical Biology , also identifies links between defects in this particular enzyme and certain cancers, potentially pointing to new targets for anticancer drugs. (bnl.gov)
  • Because of these limited therapeutic targets, many cancers, including TNBCs, are typically treated with surgery and a combination of radiation and chemotherapy that induce various types of DNA damage. (sciencedaily.com)
  • Previous MDM2 inhibitors targeted the interaction between MDM2 and p53 and were found ineffective against cancers with mutated or deficient p53. (rosalindfranklin.edu)
  • 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)
  • Until now, it has not been possible to inhibit the ubiquitin-proteasome system in a target-selective manner. (businesswire.com)
  • Sunitinib, sorafenib and pazopanib are small molecules that inhibit several protein kinases including tyrosine kinase of VEGF receptor. (czytelniamedyczna.pl)
  • Remodelin, a small-molecule compound, can specifically target and inhibit the N-acetyltransferase NAT10 [12]. (cd4inhibitors.com)
  • As part of this mechanism ATM itself, and the ATM-activated protein tyrosine kinase, c-Abl, inhibit Hdm2 function through phosphorylation of serine 395 and tyrosine 394 (Y394), respectively. (dundee.ac.uk)
  • For example, a Nature article in Gu Wei's laboratory in 2016 found that the SET protein can selectively bind to the unacetylated C-terminal domain of p53 and inhibit the transcriptional activation function of p53. (medicaltrend.org)
  • 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)
  • Next, in a classic pancreatic ductal adenocarcinoma (PDAC) model, the author once again observed the tumor suppressor effect of p53KQ/KQ. (medicaltrend.org)
  • In the absence of Wnt signaling, we found that Tcf factors associate with proteins of the Groucho family of transcriptional repressors to repress target gene transcription (9). (maquisadeoccidente.com)
  • Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates transcriptional repression of E-cadherin. (idrblab.net)
  • According to this model, it is speculated that if p53 can not be inhibited by various negative transcriptional regulatory proteins, even if its level is not significantly increased, it may be able to exert its normal tumor suppressor function. (medicaltrend.org)
  • This protein serves as a transcriptional activator of cell growth. (spandidos-publications.com)
  • The therapeutic value of augmenting protein stabilization has also been demonstrated with proteasome inhibitors. (businesswire.com)
  • In these studies, proteasome inhibitors were able to increase levels of deficient proteins across a range of targets and organ systems. (businesswire.com)
  • Described in Nature on July 18, their work challenges previous assumptions about the mechanics by which these PARP inhibitors succeed or fail to help patients. (medicalxpress.com)
  • However, some tumors that should be vulnerable to PARP inhibitors don't respond. (medicalxpress.com)
  • These improvements could include the development of screening tests to see which tumors would best respond to PARP inhibitors, or to determine which other drugs should-or should not-be given along with them, the researchers say. (medicalxpress.com)
  • There, he has established a discovery chemistry group that focuses on developing first-in-class inhibitors for newly emerging biological targets, including resistant alleles of existing targets, as well as inhibitors of well-validated targets, such as Her3 and RAS, that have previously been considered recalcitrant to small molecule drug development. (stanford.edu)
  • Occupational exposure limits with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. (cdc.gov)
  • Although intracellular signal transduction is often portrayed as a protein kinase 'domino effect', the counterbalancing function of phosphatases, and thus the control of phosphatase activity, is equally relevant to proper regulation of cellular function. (ac.be)
  • Signal transduction and targeted therapy 6 (1): 263. (cmbr-journal.com)
  • Although viewed as a constitutive housekeeping enzyme in the past, PP2A is a highly regulated phosphatase and is emerging as an important regulator of multiple cellular processes involving protein phosphorylation. (ac.be)
  • But advances in the understanding of protein phosphatases make now clear that these enzymes are precisely regulated and are as important as kinases in the regulation of cellular processes involving protein phosphorylation. (ac.be)
  • 2 Protein phosphatase 2A (PP2A) is a very abundant - it accounts for as much as 1% of total cellular proteins - ubiquitous and remarkably conserved enzyme. (ac.be)
  • PML is a protein that regulates important cellular decisions about life or death. (forth.gr)
  • Mass spectrometry-based phosphoproteomics identified thirteen protein networks distinctly regulated by DN R-Ras, including multiple networks regulating cellular movement and morphology. (biomedcentral.com)
  • Closer study of an R-Ras regulated pathway containing the signaling protein ROCK1 showed that inhibition of either R-Ras, R-Ras2 or ROCK1 similarly impaired cellular migration and invasion and altered cellular morphology. (biomedcentral.com)
  • Increasing amounts of evidence indicate that autophagy is induced by a number of stressors in tumor cells, such as starvation, growth factor deprivation, hypoxia, damage stimulation and therapeutic drugs, and is an important survival mechanism in response to cellular stress ( 9 ). (spandidos-publications.com)
  • The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
  • 2023 Nature Comm revision. (ccf.org)
  • 2023 Nature Cell Biology 25:92. (ccf.org)
  • Researchers have uncovered the mechanisms through which the blood vessel epicardial substance (BVES) protein contributes to muscular dystrophies ( Nature Communications ). (frontlinegenomics.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)
  • Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a serine/threonine kinase whose activation leads to phosphorylation cascades within the cell that lead to cell growth and proliferation. (wikipedia.org)
  • 5' adenosine-monophosphate-activated protein kinase (AMPK) has also been found to be an effector for RHEB. (wikipedia.org)
  • AMPK is a protein kinase that begins a phosphorylation cascade leading to autophagy. (wikipedia.org)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • The protein interaction landscape of the human CMGC kinase group. (nature.com)
  • Protein kinase C, an elusive therapeutic target? (tang-prize.org)
  • In the absence of Wnt signals, the cytoplasmic catenin beta-1 ( β-catenin ) is associated with a complex including auxin, glycogen synthase kinase 3 ( GSK-3 ), and adenomatous polyposis coli ( APC ) (the APC protein acts as the primary regulator of β-catenin function). (hindawi.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)
  • Especially, this allows ATP and VEGF (vascular endothelial growth factor) to be synthesized in an oxygen-independent manner, thereby promoting angiogen- esis, cell survival and tumor growth [5]. (cd4inhibitors.com)
  • We have shown that classic Ras proteins promote proliferation and survival, but not migration, in malignant peripheral nerve sheath tumor (MPNST) cells. (biomedcentral.com)
  • We assessed the expression and activation of these proteins in MPNST cells and inhibited them to determine the effect this had on proliferation, migration, invasion, survival and the phosphoproteome. (biomedcentral.com)
  • Autophagy provides energy to tumor cells for survival and metabolic reprogramming, in order to accommodate rapid cell growth and proliferation ( 8 ). (spandidos-publications.com)
  • Nowell collaborated with the late David Hungerford who, he says, "knew more about chromosomes than I did," and together they made the startling observation that individuals suffering from chronic myelogenous leukemia (CML) had an abnormally small chromosome in the tumor cells. (laskerfoundation.org)
  • The p53 tumour-suppressor protein is tightly regulated through its association with the Hdm2 E3 ligase. (dundee.ac.uk)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • Prior to the current study, the scientists already knew that Rumi modifies Notch by adding glucose molecules to the protein. (bnl.gov)
  • The two repair scaffold proteins, Ku80 and DNA-PKcs, that LINP1 links coordinate the non-homologous end-joining (NHEJ) repair molecules that fix double-strand breaks in DNA. (sciencedaily.com)
  • Stablix's RESTORED platform generates heterobifunctional small molecules (RESTORACS) that recruit deubiquitinase enzymes to remove ubiquitin from targeted proteins and consequently stabilize or increase target protein levels and activity. (businesswire.com)
  • These recruiting moieties are conjugated with linkers to targeting ligands to create bispecific molecules that co-localize a DUB and a target. (businesswire.com)
  • In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. (nature.com)
  • LACTB is a tumour suppressor that modulates lipid metabolism and cell state. (broadinstitute.org)
  • One of these target proteins … plays an important role in how cells sense their neighbors … and how much they should grow-like a master controller. (bnl.gov)
  • Importantly, the team found that blocking LINP1 significantly increases sensitivity by the tumor cells to radiation therapy. (sciencedaily.com)
  • Second, a suite of biochemical and functional assays is used to monitor the ubiquitination and functional status of target proteins in cells. (businesswire.com)
  • VEGF protein is a potent proangiogenic factor that binds to its receptor on endothelial cells. (czytelniamedyczna.pl)
  • The protein encoded by this gene is a mitogen-inducible monokine and is one of the major HIV-suppressive factors produced by CD8+ T-cells. (cancerindex.org)
  • Myeloid immune cells, specifically tumor-associated macrophages (TAMs), may represent potential novel therapeutic targets in HCC, complementing current ablative or immune therapies. (cancerindex.org)
  • unable to properly repair these breaks, BRCA -deficient tumor cells die. (medicalxpress.com)
  • For nearly a decade, scientists had known that the loss of a protein called 53BP1 made it possible for BRCA1 -deficient cells to overcome their inherent defect and properly repair double-strand breaks. (medicalxpress.com)
  • This type of resistance can emerge during or after PARP inhibitor treatment when some tumor cells thrive after mutating to lose 53BP1. (medicalxpress.com)
  • 4 While proteins can be phosphorylated on nine amino acids, serine, threonine and tyrosine phosphorylation are by far the most predominant in eukaryotic cells. (ac.be)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • Application of unidirectional pulsatile shear stress to human umbilical vein endothelial cells (HUVECs) decreased PDCD4 protein but not mRNA level. (plos.org)
  • Research at IMBB, published in Nature Aging, reveals a fundamental quality control mechanism that operates in cells to safeguard the integrity and function of the nucleus. (forth.gr)
  • In cells, p53 is a very unstable protein with a short half-life. (medicaltrend.org)
  • The traditional theory is that when cells are stimulated, the binding of MDM2 and p53 will be destroyed, leading to the accumulation of p53 protein, which affects downstream gene expression and enables cells to respond to the stimulus. (medicaltrend.org)
  • Cells were transfected with doxycycline-inducible vectors expressing either a pan-inhibitor of the R-Ras subfamily [dominant negative (DN) R-Ras] or enhanced green fluorescent protein (eGFP). (biomedcentral.com)
  • Proteins in cells with or without DN R-Ras expression were differentially labeled with SILAC and mass spectrometry was used to identify phosphoproteins and determine their relative quantities in the presence and absence of DN R-Ras. (biomedcentral.com)
  • Both proteins were activated in neurofibromin-null MPNST cells. (biomedcentral.com)
  • Here, we examined the expression, activation and action of R-Ras proteins in MPNST cells that have lost neurofibromin. (biomedcentral.com)
  • Tumor immunotherapy refers to exogenous intervention of the body's immune system, restart and maintain the "tumor-immune" cycle, restore and improve the anti-immune response of the group, strengthen the recognition and killing ability of tumor cells, so as to achieve the therapeutic effect of controlling or even clarifying the tumor specifically. (cmbr-journal.com)
  • Here, we report that aquaporin 3 (AQP3), a channel protein that mediates the transport of water/glycerol, was highly expressed in the epidermis and CD4+ T cells of both rosacea patients and experimental mice. (bvsalud.org)
  • In addition, NS5A significantly increases the expression of inducible nitric oxide synthase, cyclin D1 and nuclear factor-κB, but decreases p53 protein expression in HepG2 cells ( 6 ). (spandidos-publications.com)
  • Mutant allele frequencies were at 40-50% , suggesting that the mutation was present in most or all tumor cells. (massgenomics.org)
  • Neuroblastoma is a type of cancerous tumor composed of immature nerve cells (neuroblasts). (medlineplus.gov)
  • Researchers believe the deleted region could contain a gene that keeps cells from growing and dividing too quickly or in an uncontrolled way, called a tumor suppressor gene. (medlineplus.gov)
  • The foamy stromal cells between the capillaries stain positive for glial fibrillary acid protein and neuron-specific enolase. (medscape.com)
  • GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. (lu.se)
  • This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). (lu.se)
  • The protein is largely involved in the mTOR pathway and the regulation of the cell cycle. (wikipedia.org)
  • The protein is a lipid-anchored, cell-membrane protein with five repeats of the RAS-related GTP-binding region. (wikipedia.org)
  • Its activity is strongly regulated within the cell by tumor-suppressant proteins that form the TSC complex. (wikipedia.org)
  • This could lead to the disregulation of many signalling proteins and effectors within the cell, including RHEB. (wikipedia.org)
  • It's a protein chain that spans the cell membrane with complicated 3D folding-including 36 repeating "beads on a necklace" folds that can each be modified in different ways to affect the protein's overall function. (bnl.gov)
  • An in vivo investigation in nude mice was done to assess the anti-tumor activity of L. rhamnosus supernatant and whole-cell culture. (hindawi.com)
  • Administration of supernatant and whole-cell culture of L. rhamnosus expressively reduced tumor growth compared to the control group. (hindawi.com)
  • Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma. (broadinstitute.org)
  • A study has identified a protein that is responsible for regulation and stabilisation of the p53 tumour suppressor ( Cell Reports ). (frontlinegenomics.com)
  • The phenomenon of field cancerization (the existence of histologically abnormal tissue beyond a neoplastic area that predisposes to tumour formation) was described in the 1950s on the basis of analyses of squamous cell carcinomas (SCCs). (researchgate.net)
  • We recently found low level of tumor suppressor programmed cell death 4 (PDCD4) associated with reduced atherosclerotic plaque area (unpublished). (plos.org)
  • Proteomics-Based Discovery of First-in-Class Chemical Probes for Programmed Cell Death Protein 2 (PDCD2). (stanford.edu)
  • However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. (lu.se)
  • B-cell lymphomas (BCLs) constitute a diverse set of tially identify new functional, diagnostic, and therapeutic tumors, both morphologically and clinically, that are mainly targets. (lu.se)
  • Using a multi-omics approach, researchers have uncovered genetic drivers underpinning the formation of arachnoid cysts in the brain ( Nature Medicine ). (frontlinegenomics.com)
  • such receptors include endothelial receptor of protein C (ePCR), gC1qR, intercellular adhesion molecule-1, CD36, chondroitin sulfate A, or complement receptor 1 ( 10 ). (cdc.gov)
  • In the present study, we have identified a novel target of c-Abl in the Hdm2 protein, tyrosine 276 (Y276). (dundee.ac.uk)
  • A new study by IMBB researchers proposes that PML is a breast - tumor suppressor and can serve as a new biomarker. (forth.gr)
  • A new study published by IMBB researchers shows that a transporter, found in mosquito legs can remove the insecticide out of the organism acting like a pump.This mechanism could be targeted to restore insecticide toxicity. (forth.gr)
  • Tumor occurrence is often a slow process, so even if the content of p53 does not increase, tumors can be inhibited by increasing the activity. (medicaltrend.org)
  • It is gratifying to see the work on precise stabilization of proteins now being translated into new therapies," said Dr. Colecraft. (businesswire.com)
  • Targeted anti-mitotic therapies: can we improve on tubulin agents? (researchgate.net)
  • The advent of molecularly targeted drug discovery has facilitated the identification of a new generation of anti-mitotic therapies that target proteins with specific functions in mitosis. (researchgate.net)
  • Here, we review current knowledge of the current status of tumor immunotherapy and the types and effects of post-translational modifications of proteins, hoping to improve new ideas for the types of therapies. (cmbr-journal.com)
  • P90 ribosomal S6 kinases: A bona fide target for novel targeted anticancer therapies? (lu.se)
  • 1 Reversible protein phosphorylation is an important regulatory mechanism that controls the activities of a myriad of proteins and is thus involved in virtually every major physiological process. (ac.be)
  • Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease. (nature.com)
  • Chemokine receptor 5 (CCR5) has gained attention as therapeutic target in various malignancies. (cancerindex.org)
  • Therapeutic Target Database describing target druggability information. (idrblab.net)
  • Neurofibromin loss potentially hyperactivates classic Ras (H-Ras, N-Ras, K-Ras), M-Ras, and R-Ras (R-Ras, R-Ras2/TC21) subfamily proteins. (biomedcentral.com)
  • This function is novel and not typically associated with the Ras proteins. (wikipedia.org)
  • Our work describes the structure and function of an important enzyme called Rumi, which adds a glucose molecule to several signaling proteins to modify their activities," said the study's lead author, Huilin Li, a biologist at the U.S. Department of Energy's Brookhaven National Laboratory and Stony Brook University. (bnl.gov)
  • As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. (nature.com)
  • Stablix possesses a first-in-category platform that can restore protein stability and function in a target-selective manner," said Carlo Rizzuto, Ph.D., partner at Versant and acting CEO of Stablix. (businesswire.com)
  • In summary, the authors used p53 transgenic animal models to prove that the stability of p53 protein and the increase in protein levels are not necessary conditions for its tumor suppressor function. (medicaltrend.org)
  • Although DNA damage and other stimuli can significantly increase the level of p53 protein, this is not necessarily the case in the p53 tumor suppressor function. (medicaltrend.org)
  • Protein modification after translation enriches the diversity of protein, regulates the structure and function of a protein, and participates in more life processes. (cmbr-journal.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 expression of HIFs protein should be inhibited because it is great essential for tumor growth. (cd4inhibitors.com)
  • Toward an understanding of the protein interaction network of the human liver. (idrblab.net)
  • In the past, most of the attention was focused primarily on protein kinases and on their regulation, mainly because phosphatases were then viewed as simple housekeeping enzymes. (ac.be)
  • Zachary Mirman et al, 53BP1-RIF1-shieldin counteracts DSB resection through CST- and Polα-dependent fill-in, Nature (2018). (medicalxpress.com)
  • In patients with a history of low-grade Ta disease and a noted sub-centimeter papillary tumor(s), consider in-office fulguration as an alternative to resection under anesthesia. (medscape.com)
  • One theory is that it may have arisen as the timeframe believed to be required for healing after tumor resection. (medscape.com)
  • Drosophila RHEB is a direct target of Tsc2 GTPase-activating protein (GAP) activity both in vivo and in vitro. (signalchem.com)
  • First identified in Drosophila, the conserved Polycomb group (Pc-G) protein complexes were shown to be both writers (Polycomb Repressive Complex 2, PRC2) and readers (Polycomb Repressive Complex 1, PRC1) of H3K27me3 [ 19 , 20 , 21 ]. (biomedcentral.com)
  • Beclin l, the mammalian counterpart of the yeast Atg6 gene, is an essential protein in autophagy ( 10 ). (spandidos-publications.com)
  • Loss of the Ras GTPase-activating protein neurofibromin promotes nervous system tumor pathogenesis in patients with neurofibromatosis type 1 (NF1). (biomedcentral.com)
  • Specifically, the PDCD4 protein combines directly with the mRNA coding region of the target gene ( MYB/c-MYB ) to block translation [2] . (plos.org)
  • NS5A upregulates Beclin 1 mRNA and protein expression in a HCV NS5A-transactivated protein 9 (NS5ATP9)-dependent manner ( 15 ). (spandidos-publications.com)
  • It binds the 3′ AG splice acceptor dinucleotide of the pre-mRNA target intron, and forms a heterodimer with U2AF2 , which binds the adjacent polypyrimidine tract. (massgenomics.org)
  • This indicates that the activation of p53 does not depend on the increase in the level of p53 protein, but as long as the inhibitory effect of transcription repressor protein is released. (medicaltrend.org)
  • The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
  • We show that c-Abl phosphorylates this residue in vitro and confirm that Y394 is a target of c-Abl. (dundee.ac.uk)
  • Rheb is a 21 kDa protein monomer composed of 184 amino acids. (wikipedia.org)
  • This molecule enhances the repair of DNA breaks by serving as a scaffold that links two other proteins in the repair machinery. (sciencedaily.com)
  • They code for proteins that are important for properly repairing a DNA molecule that has been cut somewhere along its length-a mishap called a double-strand break, since it severs both strands of the DNA helix. (medicalxpress.com)
  • Immunohistochemistry in diagnostic surgical pathology: contributions of protein life-cycle, use of evidence-based methods and data normalization on interpretation of immunohistochemical stains. (lsbio.com)