• regulates
  • Here, we report that p73 stability is directly regulated by the ubiquitin-proteasome pathway.We find that p300-mediated acetylation of p73 protects it against ubiquitinylation and that PML regulates p73 stability by positively modulating its acetylation levels.As a result, PML potentiates p73 transcriptional and proapoptotic activities that are markedly impaired in Pml-/- primary cells. (nih.gov)
  • The C-Terminal domain has also been shown to be dephosphorylated by phosphatases such as Protein phosphatase 1 (PP1) in vitro and cell culture, which regulates levels of active casein kinase in vivo. (wikipedia.org)
  • There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. (wikipedia.org)
  • tyrosine
  • The most common genetic abnormality in GBMs is the activation of receptor tyrosine kinases (RTKs), of which, aberrant expression of EGFR is the most frequent ( , 2 ). (pnas.org)
  • LDL binding to T-cadherin leads to the activation of Erk 1/2 tyrosine kinase and the nuclear translocation of NF-kappaB. (wikipedia.org)
  • The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. (wikipedia.org)
  • Deletion of the second tyrosine phosphatase domain in colorectal cancer cells also reduces PTPrho catalytic activity, again demonstrating that the second phosphatase domain of PTPrho does regulate catalytic activity, either directly or indirectly. (wikipedia.org)
  • Tyrosine kinases are enzymes that add phosphates to tyrosine residues, and are the opposing enzymes to PTPs. (wikipedia.org)
  • PTEN
  • During the same period, Wigler and Nikolai Lisitsyn developed the concept and applications of representational difference analysis, which led to their identification of new cancer genes, including the tumor suppressor PTEN, and by others the cancer virus-causing Kaposi's sarcoma, KSHV. (wikipedia.org)
  • epithelial
  • The administration of ILY to ihCD59 + mice crossed with various Cre-driver lines resulted in the rapid and specific ablation of immune, epithelial, or neural cells without off-target effects. (jci.org)
  • Finally, the ILY/ihCD59-mediated cell-ablation method was tested in several disease models to study immune cell functionalities, hepatocyte and/or biliary epithelial damage and regeneration, and neural cell damage. (jci.org)
  • Ski effectively reversed transformation and epithelial-to-mesenchyme transition in cultured breast cancer cells and metastasis in TAZ-expressing xenografted tumors. (sciencemag.org)
  • Desmoglein-2 is highly expressed in epithelial cells and cardiomyocytes. (wikipedia.org)
  • This second family member, desmoglein-2 is expressed in desmosome-containing tissues, such as cardiac muscle, colon, colon carcinoma, and other simple and stratified epithelial-derived cell lines. (wikipedia.org)
  • Desmoglein-2 is an integral component of desmosomes, which are cell-cell junctions between epithelial, myocardial, and certain other cell types. (wikipedia.org)
  • SAP97 is expressed throughout the body in epithelial cells. (wikipedia.org)
  • serine
  • Upon Hippo signaling in mice, YAP is phosphorylated at a key serine (S127), confining it to the cytoplasm, where it can no longer function in target gene expression ( 7 ). (pnas.org)
  • NF2/merlin is phosphorylated on serine 518 by p21-activated kinase (PAK), a downstream effector of Rac1. (jneurosci.org)
  • The protein encoded by the casein kinase 1 epsilon gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. (wikipedia.org)
  • chromosomal
  • BMSCs cultured in the presence of low Se concentrations (5-10 nM) show reduced expression of glutathione peroxidases (GPXs), thioredoxin reductases (TRRs) and other selenoproteins, as well as the appearance of micronuclei indicative of chromosomal damage [ 18 ]. (mdpi.com)
  • The gene is overexpressed in cancers like lymphoma, leukemia, medulloblastoma and melanoma associated with chromosomal rearrangements. (wikipedia.org)
  • receptor
  • Plasma membrane localization of the EGFR could be restored in vitro by suppressing receptor endocytosis through Rho kinase inhibition. (pubmedcentralcanada.ca)
  • CD95 is a cell surface receptor of the tumor necrosis factor/nerve growth factor receptor superfamily expressed on a variety of normal and neoplastic cells ( Nagata, 1997 ). (aspetjournals.org)
  • The most striking pattern observed was a PDGF-dependent activation of at least 25 genes involved with biosynthesis and/or uptake of cholesterol and isoprenoids, including mevalonate pyrophosphate decarboxylase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, HMG-CoA reductase, and low-density lipoprotein receptor. (aacrjournals.org)
  • effector
  • Two discoveries brought cell death from obscurity to a major field of research: identification of components of the cell death control and effector mechanisms, and linkage of abnormalities in cell death to human disease, in particular cancer. (wikipedia.org)
  • vitro
  • Mutation of NF2/merlin rescued the myelin deficit in Rac1-CKO mice in vivo and the shortened processes in cultured Rac1-CKO SCs in vitro . (jneurosci.org)
  • Normal human somatic cells show virtually no spontaneous immortal transformation in vitro , whereas tumor tissues can give rise to cell lines of indefinite life span. (aacrjournals.org)
  • Additionally, normal human somatic cells in vitro and in vivo show telomere loss with successive divisions (2) , whereas most human tumor tissues and cells display telomerase activity, and most cultured human tumor cells display stabilized telomere length. (aacrjournals.org)
  • Similarly, in vitro culturing protocols for producing osteoclasts from human precursor cells in the presence of specific cytokines enables scientists to study osteoclastogenesis in human cells for translational applications. (jove.com)
  • We have proposed that ubiquilin-1 prevents inappropriate inter- and intramolecular interactions of AICD, preventing aggregation in vitro and in intact cells 4 . (jove.com)
  • STRADα stabilizes LKB1 protein both in vivo and in vitro, and is capable of eliciting multiple axons in mouse embryonic cortical cultured neurons when overexpressed with LKB1. (wikipedia.org)
  • Though T-cadherin can mediate weak adhesion in aggregation assays in vitro, the lack of intracellular domain suggests that T-cadherin is not involved in stable cell-cell adhesion. (wikipedia.org)
  • In vitro studies in HL-1 cardiomyocytes have shown that inhibition of desmoglein-2 binding or mutation of desmoglein-2 protein (Ala517Val or Val920Gly) at cardiac intercalated discs results in a reduced strength of cell-cell contact, demonstrating that desmoglein-2 is critical for cardiomyocyte cohesion. (wikipedia.org)
  • regulator
  • Intermedilysin (ILY), a cytolytic pore-forming toxin that is secreted by Streptococcus intermedius , lyses human cells exclusively by binding to the human complement regulator CD59 (hCD59), but does not react with CD59 from nonprimates. (jci.org)
  • Normally, this gene codes for the protein merlin, a regulator of cell growth, especially in Schwann cells. (ajnr.org)
  • 1994
  • Bhat RV, Baraban JM, Johnson RC, Eipper BA, Mains RE (1994) High levels of expression of the tumor suppressor gene APC during development of the rat central nervous system. (springer.com)
  • 1994) A targeted chain-termination mutation in the mouse Apc gene results in multiple intestinal tumors. (springer.com)
  • In 1994, Matthew Meyerson and Ed Harlow investigated the product of a close analogous gene of CDK4. (wikipedia.org)
  • Four years later, after an international race to find it, the gene was cloned in 1994 by scientists at University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics. (wikipedia.org)
  • 1995
  • The human CK1ε was first isolated and cloned in 1995, officially identified as an isoform of the casein kinase 1 family. (wikipedia.org)
  • progression
  • The Apc gene product (APC), basically a cytoplasmic protein, blocks cell cycle progression and plays crucial roles in development. (springer.com)
  • Expression of PDGF-A is increased in glioblastoma ( 10 ), suggesting a specific role in tumor progression. (aacrjournals.org)
  • Overcoming p57-mediated growth inhibition in these cells may be crucial for acquisition of the unlimited growth potential thought to be critical for malignant progression. (aacrjournals.org)
  • Cellular growth control is regulated by a group of conserved CDKs, 3 which govern entry into and progression through the cell cycle. (aacrjournals.org)
  • Thought to play a biological role in controlling cell growth and progression of various cancers. (mybiosource.com)
  • We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. (sciencemag.org)
  • CDK family members are highly similar to the gene products of Saccharomyces cerevisiae cdc28, and Schizosaccharomyces pombe cdc2, and are known to be important regulators of cell cycle progression in the point of regulation named R or restriction point. (wikipedia.org)
  • tumors
  • The adenomatous polyposis coli (Apc) gene is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. (springer.com)
  • Most of the mutated Apc genes in colorectal tumors lack β-catenin-binding regions and fail to inhibit Wnt signaling, leading to overproliferation of tumor cells. (springer.com)
  • Analysis of an expression databank derived from human glial tumors ( n = 77) identified a subgroup exhibiting a profile consistent with PDGF dependence, including increased expression of SRE-BP target genes. (aacrjournals.org)
  • However, the genes regulated by PDGF autocrine signaling in glial tumors remain unknown. (aacrjournals.org)
  • Chemotherapeutic drugs have a hard time penetrating tumors to kill them at their core because these cells may lack a good blood supply. (wikipedia.org)
  • This work led to the first successful sequence-based analysis of the genomes of single cancer cells from tumors by Wigler's then-graduate student Nick Navin, and subsequently, tumor cells in circulation by Wigler's collaborator Jim Hicks. (wikipedia.org)
  • Cyclin
  • The presence of full-length PTPkappa in melanoma cells decreases the level of free-cytosolic β-catenin, which consequently reduces the level of nuclear β-catenin and reduces the expression of the β-catenin-regulated genes, cyclin D1 and c-myc. (wikipedia.org)
  • The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
  • the cyclin D. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (wikipedia.org)
  • CEBPA has been shown to interact with Cyclin-dependent kinase 2 and Cyclin-dependent kinase 4. (wikipedia.org)
  • intracellular
  • Because the presence of PTPkappa at the cell membrane was shown to sequester β-catenin to the plasma membrane, these data suggest that one mechanism whereby PTPkappa functions as a tumor suppressor is by regulating the intracellular localization of free-β-catenin. (wikipedia.org)
  • vivo
  • The minicircle DNA delivery gene transfer system provides an alternative method to establish an osteoporosis-related model is particularly useful to study the efficacy of various pharmacological inhibitors in vivo . (jove.com)
  • In vivo T-cadherin was detected on the apical cell surface of the chick interstinal epithelium. (wikipedia.org)
  • localization
  • Brakeman JSF, Gu SH, Wang XB, Dolin G, Baraban JM (1999) Neuronal localization of the adenomatous polyposis coli tumor suppressor protein. (springer.com)
  • Neither proteolytic activation nor nuclear localization of SRE-BP was affected by disruption of the PDGF autocrine loop, indicating that PDGF signaling is required for other signaling events involved in activation of SRE-BP target genes. (aacrjournals.org)
  • allele
  • DNA and RNA analysis of mass populations and individual subclones of conditionally immortal HMEC line 184A1 showed that continued growth of conditionally immortal cells with critically short telomeres was repeatedly accompanied by loss of the expressed p57 allele and transient expression of the allele imprinted previously. (aacrjournals.org)
  • The p57 gene has been found to be imprinted with preferential expression of the maternal allele (9) , suggesting that loss of the maternal allele by itself may severely reduce p57 expression. (aacrjournals.org)
  • Regulation
  • Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P (1998) Down regulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. (springer.com)
  • These findings indicated that ZIPK may also be involved in the regulation of the cell cycle in human cells, by interacting with HsCdc14A. (antibodies-online.com)
  • The AICD is also liberated from the membrane after secretase processing, and through interactions with Fe65 and Tip60, can translocate to the nucleus to participate in transcription regulation of multiple target genes 2,3 . (jove.com)
  • Neurofibromatosis types 1 and 2 are a group of neurocutaneous syndromes resulting from disorders in cell regulation. (ajnr.org)
  • Merlin is quite atypical for a tumor-suppressor gene because it localizes to the cell membrane for regulation. (ajnr.org)
  • Classical cadherins are necessary for cell-cell contacts, dynamic regulation of morphogenetic processes in embryos and tissue integrity in adult organism. (wikipedia.org)
  • inhibits
  • 4 A key method by which merlin inhibits cell growth is via contact-dependent inhibition. (ajnr.org)
  • This autophosphorylation occurs in the protein's C-Terminal domain, a region believed to behave as a pseudosubstrate, and inhibits kinase activity. (wikipedia.org)
  • embryonic
  • In response to extrinsic cues, embryonic epidermal cells either stratify to produce the protective barrier at the skin surface or invaginate to form hair follicles (HFs) ( 13 ). (pnas.org)
  • Mice generated from these ES cells were viable, suggesting that PTPkappa phosphatase activity is not necessary for embryonic development. (wikipedia.org)
  • activation
  • Studies of the activation of signaling events in these GBM tumor cells revealed notable differences between wild-type and vIII EGFR-expressing cells. (pnas.org)
  • We also show that EGFR-mediated tumor formation is accompanied by the activation of canonical and unexpected signaling pathways. (pnas.org)
  • The poor responsiveness of mutant KRAS tumor cells to EGFR inhibition and activation was accompanied by a reduced capacity of these cells to bind and internalize EGF and by a failure to retain EGFR at the plasma membrane. (pubmedcentralcanada.ca)
  • FLICE then transmits the activation signal to ICE and CPP32 (caspase 3), which is thought to trigger cell death. (aspetjournals.org)
  • RhoA/ROCK activation is necessary for cell contraction, stress fiber assembly and inhibition of spreading, while Rac is required for the formation of membrane protrusions and actin-rich lamellopodia at the leading edge of migrating cells. (wikipedia.org)
  • Adiponectin binding to T-cadherin on vascular cells is associated with NF-kappa B activation. (wikipedia.org)
  • human
  • Here, we took advantage of this feature of ILY and developed a model of conditional and targeted cell ablation by generating floxed STOP- CD59 knockin mice ( ihCD59 ), in which expression of human CD59 only occurs after Cre-mediated recombination. (jci.org)
  • The p53 tumor suppressor gene ( TP53 ) is the most frequently altered gene in human cancer and also is found mutated in human gliomas. (aspetjournals.org)
  • More recently, the newly discovered PDGF-C and PDGF-D subunits were also shown to be expressed at high frequency in glioblastoma-derived cell lines and primary human tumor tissues ( 11 ). (aacrjournals.org)
  • A clonal population of human somatic cells is unlikely to accumulate a sufficient number of errors required for tumorigenicity within the 50-100 population doubling limit that replicative senescence imposes. (aacrjournals.org)
  • Thus, Ski inhibited the function of TAZ through multiple mechanisms in human cancer cells. (sciencemag.org)
  • Protein kinase LYK5, also known as LYK5 or STRADα, is a human protein and also denotes the gene encoding it. (wikipedia.org)
  • Following the identification of a Pur factor, which specifically bound a purine-rich sequence in the control region of the c-MYC gene, the gene, PURA, encoding the protein, Pur-alpha, was cloned and sequenced for both human and mouse (GenBank U02098.1). (wikipedia.org)
  • After moving to CSHL, Wigler continued his studies of gene transfer into mammalian cells, exploring the integration of foreign DNA and its stability of expression in host cells, demonstrating the inheritance of DNA methylation patterns, and isolating the first vertebrate genes, and first human oncogenes, using DNA transfer and genetic selection. (wikipedia.org)
  • BRCA1 and BRCA1 (/ˌbrækəˈwʌn/) are a human gene and its protein product, respectively. (wikipedia.org)
  • nuclear
  • p21 may also directly block DNA replication by inhibiting the proliferating cell nuclear antigen (PCNA), an essential DNA replication protein. (cshl.edu)
  • activity
  • Indeed, p73α transcriptional activity was diminished up to 65% in Pml−/− cells (Fig. 7 A and not depicted). (nih.gov)
  • Resensitization was accompanied by an acquired dependency on the EGFR for maintaining basal extracellular signal-regulated kinase (ERK) activity. (pubmedcentralcanada.ca)
  • With continued passage, the conditionally immortal cell populations very gradually converted to a fully immortal phenotype of good uniform growth, expression of high levels of telomerase activity, and stabilization of telomere length. (aacrjournals.org)
  • Nucleoside diphosphate kinase activity involves the transfer of the γ-phosphate of nucleoside triphosphate (NTP) to nucleoside diphosphate (NDP), where N1 and N2 can be ribo- or deoxyribonucleosides. (wikipedia.org)
  • This SNP would result in less REST repressor activity, which could lead to increased expression of PTPrho (PTPRT) in cells that harbored this SNP. (wikipedia.org)
  • If the transgene was incorporated into a gene with a signal sequence, β-gal activity would remain in the cytosol of the cell and therefore be active. (wikipedia.org)
  • If the reporter gene was incorporated into a gene that lacked a signal sequence, β-gal activity would be in the ER where it would lose β-gal activity. (wikipedia.org)
  • There are additional functions of CDK6 not associated with its kinase activity. (wikipedia.org)
  • As previously stated, the C-Terminal domain of casein kinase 1 epsilon behaves as a pseudosubstrate when phosphorylated, inhibiting kinase activity. (wikipedia.org)
  • glial
  • The mechanisms involved are poorly understood but are likely to involve coordinated changes in the glial cell cytoskeleton. (jneurosci.org)
  • These dramatic morphogenetic events are likely to reflect major changes in the organization of the glial cell actin cytoskeleton. (jneurosci.org)
  • Cultured neoplastic glial cells are rather resistant to most proapoptotic stimuli ( Weller, 1996 ). (aspetjournals.org)
  • mammalian
  • Wigler's laboratory was the first to demonstrate that some regulatory pathways have been so conserved in evolution that yeast can be used as a host to study the function of mammalian genes and in particular genes involved in signal transduction pathways and cancer. (wikipedia.org)
  • In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. (wikipedia.org)
  • Daily oscillations in protein and mRNA transcription have been observed in many cells, including the mammalian master clock known as the suprachiasmatic nucleus (SCN). (wikipedia.org)
  • molecular
  • From a molecular standpoint, GBMs are a highly heterogeneous tumor with multiple signaling pathways differentially activated or silenced with converging and parallel complex interactions ( 2 ). (pnas.org)
  • Our findings demonstrate that PML plays a crucial role in modulating p73 function, thus providing further insights on the molecular network for tumor suppression. (nih.gov)
  • PMID
  • PMID 6251468 Commercial application of these discoveries follows from Axel-Wigler-Silverstein patent application (U.S. 4,399,216) filed February 20, 1980, entitled, "Process for Inserting DNA into Eucaryotic Cells and for Producing Proteinaceous Materials. (wikipedia.org)
  • mice
  • In organized studies of new treatments for cancer, the pre-clinical development of drugs, devices, and techniques begins in laboratories, either with isolated cells or in small animals, most commonly rats or mice. (wikipedia.org)
  • These mice exhibited white plaque-like lesions in cardiac muscle as early as 2 weeks, displaying a cardiac phenotype by 4 weeks that involved loss of viable cardiomyocytes and heavy cell calcification. (wikipedia.org)
  • Mice in which the SAP97 gene has been knocked out die perinatally, have a cleft palate, and deficiencies in renal function. (wikipedia.org)
  • transcription
  • Accordingly, Bax and p21 protein levels were enhanced by coexpression of p73 and PML as compared with cells expressing p73 alone (Fig. S5 C). Pml inactivation resulted in a marked impairment of p73-dependent transcription. (nih.gov)
  • BMAL1 and CLOCK work to increase PER and CRY transcription by binding on the E-box domain upstream from the PER and CRY gene coding sequences. (wikipedia.org)
  • mutation
  • The gene was later mapped and identified by Joseph Takahashi and colleagues, which revealed a single base-pair C-to-T substitutional mutation in the hamster CK1ε gene. (wikipedia.org)
  • Mutation of the CEBPA gene has been shown to play a crucial role in leukemogenesis and prognosis in acute myeloid leukemia patients. (wikipedia.org)
  • migration
  • Depletion of ZIPK resulted in impairment of cultured VSMC migration and contraction. (antibodies-online.com)
  • It is involved in low density lipoproteins (LDL) hormone-like effects on Ca2+-mobilization and increased cell migration as well as phenotype changes. (wikipedia.org)
  • T-cadherin overexpression in ECs facilitates spontaneous cell migration, formation of stress fibers and change of the phenotype from quiescent to promigratory. (wikipedia.org)
  • T-cadherin expression results in LDL-induced migration of T-cadherin expressing cells compared to control. (wikipedia.org)
  • deletion
  • Concomitant with EGFR gene amplification events is the occurrence of an intragenic in-frame deletion of exons 2−7 of the EGFR gene. (pnas.org)
  • subfamily
  • PTPrho does not bind to other subfamily members to mediate cell-cell aggregation, similar to other type R2B subfamily members. (wikipedia.org)
  • Currently, four desmoglein subfamily members have been identified and all are members of the cadherin cell adhesion molecule superfamily. (wikipedia.org)
  • interacts
  • PTPrho protein mediates homophilic cell-cell adhesion, meaning that when it interacts with a like molecule on an adjacent cell it induces the cells to bind or adhere to one another. (wikipedia.org)
  • PTPkappa interacts by co-immunoprecipitation with E-cadherin, α-catenin and β-catenin in pancreatic acinar cells prior to the dissolution of adherens junctions in a rat model of pancreatitis. (wikipedia.org)
  • enzymes
  • Nucleoside-diphosphate kinases (NDPKs, also NDP kinase, (poly)nucleotide kinases and nucleoside diphosphokinases) are enzymes that catalyze the exchange of terminal phosphate between different nucleoside diphosphates (NDP) and triphosphates (NTP) in a reversible manner to produce nucleotide triphosphates. (wikipedia.org)