Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.
A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.
A gene product of the p16 tumor suppressor gene (GENES, P16). It antagonizes the function of MDM2 PROTEIN (which regulates P53 TUMOR SUPPRESSOR PROTEIN by targeting it for degradation). p14ARF is produced from the beta mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced alpha transcript, is CYCLIN-DEPENDENT KINASE INHIBITOR P16. Both p16 gene products have tumor suppressor functions.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
A cell line derived from cultured tumor cells.
An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A membrane protein homologous to the ERM (Ezrin-Radixin-Moesin) family of cytoskeleton-associated proteins which regulate physical properties of membranes. Alterations in neurofibromin 2 are the cause of NEUROFIBROMATOSIS 2.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A negative regulator of beta-catenin signaling which is mutant in ADENOMATOUS POLYPOSIS COLI and GARDNER SYNDROME.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Established cell cultures that have the potential to propagate indefinitely.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
Genes that have a suppressor allele or suppressor mutation (SUPPRESSION, GENETIC) which cancels the effect of a previous mutation, enabling the wild-type phenotype to be maintained or partially restored. For example, amber suppressors cancel the effect of an AMBER NONSENSE MUTATION.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A class of enzymes that catalyze the formation of a bond between two substrate molecules, coupled with the hydrolysis of a pyrophosphate bond in ATP or a similar energy donor. (Dorland, 28th ed) EC 6.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
A family of structurally related proteins that are induced by CYTOKINES and negatively regulate cytokine-mediated SIGNAL TRANSDUCTION PATHWAYS. SOCS proteins contain a central SH2 DOMAIN and a C-terminal region of homology known as the SOCS box.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
Transport proteins that carry specific substances in the blood or across cell membranes.
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).
Tumors or cancers of the KIDNEY.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
ONCOGENE PROTEINS from papillomavirus that deregulate the CELL CYCLE of infected cells and lead to NEOPLASTIC CELL TRANSFORMATION. Papillomavirus E7 proteins have been shown to interact with various regulators of the cell cycle including RETINOBLASTOMA PROTEIN and certain cyclin-dependent kinase inhibitors.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Isoforms encoded by the WT1 Wilms tumor suppressor gene (GENES, WILMS TUMOR) and produced by alternative splicings. They are zinc finger-containing transcription factors involved in both transactivation and repression, and are critical for normal development and function of the urogenital tract.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. It contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Tumors or cancer of the human BREAST.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
DNA present in neoplastic tissue.
The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Tumor suppressor genes located on human chromosome 13 in the region 13q14 and coding for a family of phosphoproteins with molecular weights ranging from 104 kDa to 115 kDa. One copy of the wild-type Rb gene is necessary for normal retinal development. Loss or inactivation of both alleles at this locus results in retinoblastoma.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Human COLORECTAL CARCINOMA cell line.
Tumor suppressor genes located on the long arm of human chromosome 22. Mutation or loss of these genes causes NEUROFIBROMATOSIS 2.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. RBL2 contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and E2F5 TRANSCRIPTION FACTOR. RBL2 also interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Proteins prepared by recombinant DNA technology.
A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
An autosomal dominant disorder characterized by a high incidence of bilateral acoustic neuromas as well as schwannomas (NEURILEMMOMA) of other cranial and peripheral nerves, and other benign intracranial tumors including meningiomas, ependymomas, spinal neurofibromas, and gliomas. The disease has been linked to mutations of the NF2 gene (GENES, NEUROFIBROMATOSIS 2) on chromosome 22 (22q12) and usually presents clinically in the first or second decade of life.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of "v-" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix "c-" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Transplantation between animals of different species.
An autosomal dominant disorder caused by mutations in a tumor suppressor gene. This syndrome is characterized by abnormal growth of small blood vessels leading to a host of neoplasms. They include HEMANGIOBLASTOMA in the RETINA; CEREBELLUM; and SPINAL CORD; PHEOCHROMOCYTOMA; pancreatic tumors; and renal cell carcinoma (see CARCINOMA, RENAL CELL). Common clinical signs include HYPERTENSION and neurological dysfunctions.
A malignant epithelial tumor with a glandular organization.
A protein found most abundantly in the nervous system. Defects or deficiencies in this protein are associated with NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome. Mutations in the gene (GENE, NEUROFIBROMATOSIS 1) affect two known functions: regulation of ras-GTPase and tumor suppression.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Proteins transcribed from the E1A genome region of ADENOVIRUSES which are involved in positive regulation of transcription of the early genes of host infection.
A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.
A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Tumors or cancer of the LIVER.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Tumor suppressor genes located in the 5q21 region on the long arm of human chromosome 5. The mutation of these genes is associated with familial adenomatous polyposis (ADENOMATOUS POLYPOSIS COLI) and GARDNER SYNDROME, as well as some sporadic colorectal cancers.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
Proteins transcribed from the E1B region of ADENOVIRUSES which are involved in regulation of the levels of early and late viral gene expression.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.
Elements of limited time intervals, contributing to particular results or situations.
Tumors or cancer of the COLON.
Proteins, protein complexes, or glycoproteins secreted by suppressor T-cells that inhibit either subsequent T-cells, B-cells, or other immunologic phenomena. Some of these factors have both histocompatibility (I-J) and antigen-specific domains which may be linked by disulfide bridges. They can be elicited by haptens or other antigens and may be mass-produced by hybridomas or monoclones in the laboratory.
Tumors or cancer of the SKIN.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
Proteins transcribed from the E4 region of ADENOVIRUSES. The E4 19K protein transactivates transcription of the adenovirus E2F protein and complexes with it.
A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104)
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.
RNA present in neoplastic tissue.
Tumors or cancer of the LUNG.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
Formation of an acetyl derivative. (Stedman, 25th ed)
A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182)
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Deletion of sequences of nucleic acids from the genetic material of an individual.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A family of small, non-enveloped DNA viruses infecting birds and most mammals, especially humans. They are grouped into multiple genera, but the viruses are highly host-species specific and tissue-restricted. They are commonly divided into hundreds of papillomavirus "types", each with specific gene function and gene control regions, despite sequence homology. Human papillomaviruses are found in the genera ALPHAPAPILLOMAVIRUS; BETAPAPILLOMAVIRUS; GAMMAPAPILLOMAVIRUS; and MUPAPILLOMAVIRUS.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Genes at loci that are involved in the development of WILMS TUMOR. Included are human WT1 at 11p13 and human WT2 (MTACR1) at 11p15.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Biochemical identification of mutational changes in a nucleotide sequence.
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Gated transport mechanisms by which proteins or RNA are moved across the NUCLEAR MEMBRANE.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
Any method used for determining the location of and relative distances between genes on a chromosome.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.

Phenotypic analysis of human glioma cells expressing the MMAC1 tumor suppressor phosphatase. (1/11830)

MMAC1, also known as PTEN or TEP-1, was recently identified as a gene commonly mutated in a variety of human neoplasias. Sequence analysis revealed that MMAC1 harbored sequences similar to those found in several protein phosphatases. Subsequent studies demonstrated that MMAC1 possessed in vitro enzymatic activity similar to that exhibited by dual specificity phosphatases. To characterize the potential cellular functions of MMAC1, we expressed wild-type and several mutant variants of MMAC1 in the human glioma cell line, U373, that lacks endogenous expression. While expression of wild-type MMAC1 in these cells significantly reduced their growth rate and saturation density, expression of enzymatically inactive MMAC1 significantly enhanced growth in soft agar. Our observations indicate that while wild-type MMAC1 exhibits activities compatible with its proposed role as a tumor suppressor, cellular expression of MMAC1 containing mutations in the catalytic domain may yield protein products that enhance transformation characteristics.  (+info)

Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences. (2/11830)

Malignant glial tumors (anaplastic astrocytomas and glioblastomas multiforme) arise mostly either from the progression of low grade precursor lesions or rapidly in a de novo fashion and contain distinct genetic alterations. There is, however, a third subset of malignant gliomas in which genetic lesions remain to be identified. Following surgical resection, all gliomas appear to have an inherent tendency to recur. Comparative molecular analysis of ten primary malignant gliomas (three anaplastic astrocytomas and seven glioblastomas multiforme) with their recurrences identified two distinct subgroups of recurrent tumors. In one group, primary tumors harbored genetic aberrations frequently associated with linear progression or de novo formation pathways of glial tumorigenesis and maintained their genetic profiles upon recurrence. In the other subset with no detectable known genetic mutations at first presentation, the recurrent tumors sustained specific abnormalities associated with pathways of linear progression or de novo formation. These included loss of genes on chromosomes 17 and 10, mutations in the p53 gene, homozygous deletion of the DMBTA1 and p16 and/ or p15 genes and amplification and/or overexpression of CDK4 and alpha form of the PDGF receptor. Recurrent tumors from both groups also displayed an abnormal expression profile of the metalloproteinase, gel A, and its inhibitor, TIMP-2, consistent with their highly invasive behavior. Delineation of the molecular differences between malignant glioblastomas and their subsequent recurrences may have important implications for the development of rational clinical approaches for this neoplasm that remains refractory to existing therapeutic modalities.  (+info)

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (3/11830)

The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules.  (+info)

The significance of tetramerization in promoter recruitment by Stat5. (4/11830)

Stat5a and Stat5b are rapidly activated by a wide range of cytokines and growth factors, including interleukin-2 (IL-2). We have previously shown that these signal transducers and activators of transcription (STAT proteins) are key regulatory proteins that bind to two tandem gamma interferon-activated site (GAS) motifs within an IL-2 response element (positive regulatory region III [PRRIII]) in the human IL-2Ralpha promoter. In this study, we demonstrate cooperative binding of Stat5 to PRRIII and explore the molecular basis underlying this cooperativity. We demonstrate that formation of a tetrameric Stat5 complex is essential for the IL-2-inducible activation of PRRIII. Stable tetramer formation of Stat5 is mediated through protein-protein interactions involving a tryptophan residue conserved in all STATs and a lysine residue in the Stat5 N-terminal domain (N domain). The functional importance of tetramer formation is shown by the decreased levels of transcriptional activation associated with mutations in these residues. Moreover, the requirement for STAT protein-protein interactions for gene activation from a promoter with tandemly linked GAS motifs can be relieved by strengthening the avidity of protein-DNA interactions for the individual binding sites. Taken together, these studies demonstrate that a dimeric but tetramerization-deficient Stat5 protein can activate only a subset of target sites. For functional activity on a wider range of potential recognition sites, N-domain-mediated oligomerization is essential.  (+info)

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (5/11830)

To investigate the mode of action of the p16(INK4a) tumor suppressor protein, we have established U2-OS cells in which the expression of p16(INK4a) can be regulated by addition or removal of isopropyl-beta-D-thiogalactopyranoside. As expected, induction of p16(INK4a) results in a G1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein (pRb) by the cyclin-dependent kinases CDK4 and CDK6. However, induction of p16(INK4a) also causes marked inhibition of CDK2 activity. In the case of cyclin E-CDK2, this is brought about by reassortment of cyclin, CDK, and CDK-inhibitor complexes, particularly those involving p27(KIP1). Size fractionation of the cellular lysates reveals that a substantial proportion of CDK4 participates in active kinase complexes of around 200 kDa. Upon induction of p16(INK4a), this complex is partly dissociated, and the majority of CDK4 is found in lower-molecular-weight fractions consistent with the formation of a binary complex with p16(INK4a). Sequestration of CDK4 by p16(INK4a) allows cyclin D1 to associate increasingly with CDK2, without affecting its interactions with the CIP/KIP inhibitors. Thus, upon the induction of p16(INK4a), p27(KIP1) appears to switch its allegiance from CDK4 to CDK2, and the accompanying reassortment of components leads to the inhibition of cyclin E-CDK2 by p27(KIP1) and p21(CIP1). Significantly, p16(INK4a) itself does not appear to form higher-order complexes, and the overwhelming majority remains either free or forms binary associations with CDK4 and CDK6.  (+info)

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (6/11830)

The response of the uterine epithelium to female sex steroid hormones provides an excellent model to study cell proliferation in vivo since both stimulation and inhibition of cell proliferation can be studied. Thus, when administered to ovariectomized adult mice 17beta-estradiol (E2) stimulates a synchronized wave of DNA synthesis and cell division in the epithelial cells, while pretreatment with progesterone (P4) completely inhibits this E2-induced cell proliferation. Using a simple method to isolate the uterine epithelium with high purity, we have shown that E2 treatment induces a relocalization of cyclin D1 and, to a lesser extent, cdk4 from the cytoplasm into the nucleus and results in the orderly activation of cyclin E- and cyclin A-cdk2 kinases and hyperphosphorylation of pRb and p107. P4 pretreatment did not alter overall levels of cyclin D1, cdk4, or cdk6 nor their associated kinase activities but instead inhibited the E2-induced nuclear localization of cyclin D1 to below the control level and, to a lesser extent, nuclear cdk4 levels, with a consequent inhibition of pRb and p107 phosphorylation. In addition, it abrogated E2-induced cyclin E-cdk2 activation by dephosphorylation of cdk2, followed by inhibition of cyclin A expression and consequently of cyclin A-cdk2 kinase activity and further inhibition of phosphorylation of pRb and p107. P4 is used therapeutically to oppose the effect of E2 during hormone replacement therapy and in the treatment of uterine adenocarcinoma. This study showing a novel mechanism of cell cycle inhibition by P4 may provide the basis for the development of new antiestrogens.  (+info)

Functions of cyclin A1 in the cell cycle and its interactions with transcription factor E2F-1 and the Rb family of proteins. (7/11830)

Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.  (+info)

p27 is involved in N-cadherin-mediated contact inhibition of cell growth and S-phase entry. (8/11830)

In this study the direct involvement of cadherins in adhesion-mediated growth inhibition was investigated. It is shown here that overexpression of N-cadherin in CHO cells significantly suppresses their growth rate. Interaction of these cells and two additional fibroblastic lines with synthetic beads coated with N-cadherin ligands (recombinant N-cadherin ectodomain or specific antibodies) leads to growth arrest at the G1 phase of the cell cycle. The cadherin-reactive beads inhibit the entry into S phase and the reduction in the levels of cyclin-dependent kinase (cdk) inhibitors p21 and p27, following serum-stimulation of starved cells. In exponentially growing cells these beads induce G1 arrest accompanied by elevation in p27 only. We propose that cadherin-mediated signaling is involved in contact inhibition of growth by inducing cell cycle arrest at the G1 phase and elevation of p27 levels.  (+info)

The QMSP analysis of RASSF1A hypermethylation enabled a highly specific distinction between patients diagnosed with lung cancer and those with nonneoplastic lung disease. These results suggested that a QMSP assay is a promising molecular tool for diagnosis of primary lung cancer.
INVOLVED IN endosomal transport (ortholog); intracellular transport (ortholog); protein targeting (ortholog); FOUND IN cytosol (ortholog); endosome (ortholog); extracellular exosome (ortholog)
The classical Ras-association domain family (RASSF1-6) are a group of Ras effector molecules that contain a C-terminal Ras-association (RA) domain of the RalGDS/AF-6 variety and a protein interaction domain known as the Sav/RASSF/Hippo (SARAH) domain. Several members of the classical RASSF family are involved in tumorigenesis since epigenetic inactivation of many isoforms is a frequent event across many tumor types and their functions are consistent with roles as tumor suppressor proteins. Recently several additional RA-domain containing family members have been identified and designated N-terminal RASSF proteins (RASSF7-10). These comprise RASSF7 (also known as HRC1 located 11p15.5), RASSF8 (also known as HOJ-1 or C12ORF2 located 12p12.1), RASSF9 (also known as P-CIP1 or PAMCI located 12q21.31) and RASSF10 (located 11p15.2). These proteins are divergent and structurally distinct from RASSF1-6, containing an RA domain within their extreme N-termini and lacking the SARAH protein interaction ...
The mechanism by which Wnt receptors transduce signals to activate downstream beta-catenin-mediated target gene transcription remains incompletely understood but involves Frizzled (Fz) receptor-mediated plasma membrane recruitment and activation of the cytoplasmic effector Dishevelled (Dvl). Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling. Depletion of CYLD from cultured cells markedly enhances Wnt-induced accumulation of beta-catenin and target gene activation. Moreover, we demonstrate hyperactive Wnt signaling in human cylindroma skin tumors that arise from mutations in CYLD. At the molecular level, CYLD interacts with and regulates K63-linked ubiquitination of Dvl. Enhanced ubiquitination of the polymerization-prone DIX domain in CYLD-deficient cells positively links to the signaling activity of Dvl. Together, our results argue that loss of CYLD instigates tumor growth in
MicroRNAs (miRNAs) play key roles in tumorigenesis and progression of gastric cancer (GC). miR-1269 has been reported to be upregulated in several cancers and plays a crucial role in carcinogenesis and cancer progression. However, the biological function of miR-1269 in human GC and its mechanism remain unclear and need to be further elucidated. The expression of miR-1269 in GC tissues and cell lines was detected by quantitative real-time PCR (qRT-PCR). Target prediction programs (TargetScanHuman 7.2 and miRBase) and a dual-luciferase reporter assay were used to confirm that Ras-association domain family 9 (RASSF9) is a target gene of miR-1269. The expression of RASSF9 was measured by qRT-PCR and Western blotting in GC tissues. MTT and cell counting assays were used to explore the effect of miR-1269 on GC cell proliferation. The cell cycle and apoptosis were measured by flow cytometry. RASSF9 knockdown and overexpression were used to further verify the function of the target gene. We found that miR-1269
Defective apoptosis contributes to the development of various human malignancies. The kinases nuclear Dbf2-related 1 (NDR1) and NDR2 mediate apoptosis downstream of the tumor suppressor proteins RASSF1A (Ras association domain family member 1A) and MST1 (mammalian Ste20-like kinase 1). To further analyze the role of NDR1 in apoptosis, we generated NDR1-deficient mice. Although NDR1 is activated by both intrinsic and extrinsic proapoptotic stimuli, which indicates a role for NDR1 in regulating apoptosis, NDR1-deficient T cells underwent apoptosis in a manner similar to that of wild-type cells in response to different proapoptotic stimuli. Analysis of the abundances of NDR1 and NDR2 proteins revealed that loss of NDR1 was functionally compensated for by an increase in the abundance of NDR2 protein. Despite this compensation, NDR1−/− and NDR1+/− mice were more prone to the development of T cell lymphomas than were wild-type mice. Tumor development in mice and humans was accompanied by a ...
Complete information for RASSF8 gene (Protein Coding), Ras Association Domain Family Member 8, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for RASSF3 gene (Protein Coding), Ras Association Domain Family Member 3, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
mouse Rassf3 protein: mouse homolog of the putative tumor suppressor gene RASSF1; about 60% homology at the amino acid level, possibly involved in Ras-like signaling pathways; RefSeq NM_138956
TSC22D4 is a member of the TSC22 domain family of leucine zipper transcriptional regulators (see TSC22D3; MIM 300506) (Kester et al., 1999 [PubMed 10488076]; Fiorenza et al., 2001 [PubMed 11707329]).[supplied by OMIM, Mar 2008 ...
GLTSCR1 - GLTSCR1 (untagged)-Human glioma tumor suppressor candidate region gene 1 (GLTSCR1) available for purchase from OriGene - Your Gene Company.
Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation.
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Homo sapiens Ras association (RalGDS/AF-6) domain family 5 (RASSF5), transcript variant 1, mRNA. (H00083593-R01) - Products - Abnova
Homo sapiens Ras association (RalGDS/AF-6) domain family 1 (RASSF1), transcript variant F, mRNA. (H00011186-R06) - Products - Abnova
MDDDDDSCLLDLIGDPQALNYFLHGPSNKSSNDDLTNAGYSAANSNSIFANSSNADPKSSLKGVSNQLGE 1 - 70 GPSDGLPLSSSLQFLEDELESSPLPDLTEDQPFDILQKSLQEANITEQTLAEEAYLDASIGSSQQFAQAQ 71 - 140 LHPSSSASFTQASNVSNYSGQTLQPIGVTHVPVGASFASNTVGVQHGFMQHVGISVPSQHLSNSSQISGS 141 - 210 GQIQLIGSFGNHPSMMTINNLDGSQIILKGSGQQAPSNVSGGLLVHRQTPNGNSLFGNSSSSPVAQPVTV 211 - 280 PFNSTNFQTSLPVHNIIIQRGLAPNSNKVPINIQPKPIQMGQQNTYNVNNLGIQQHHVQQGISFASASSP 281 - 350 QGSVVGPHMSVNIVNQQNTRKPVTSQAVSSTGGSIVIHSPMGQPHAPQSQFLIPTSLSVSSNSVHHVQTI 351 - 420 NGQLLQTQPSQLISGQVASEHVMLNRNSSNMLRTNQPYTGPMLNNQNTAVHLVSGQTFAASGSPVIANHA 421 - 490 SPQLVGGQMPLQQASPTVLHLSPGQSSVSQGRPGFATMPSVTSMSGPSRFPAVSSASTAHPSLGSAVQSG 491 - 560 SSGSNFTGDQLTQPNRTPVPVSVSHRLPVSSSKSTSTFSNTPGTGTQQQFFCQAQKKCLNQTSPISAPKT 561 - 630 TDGLRQAQIPGLLSTTLPGQDSGSKVISASLGTAQPQQEKVVGSSPGHPAVQVESHSGGQKRPAAKQLTK 631 - 700 GAFILQQLQRDQAHTVTPDKSHFRSLSDAVQRLLSYHVCQGSMPTEEDLRKVDNEFETVATQLLKRTQAM 701 - 770 LNKYRCLLLEDAMRINPSAEMVMIDRMFNQEERASLSRDKRLALVDPEGFQADFCCSFKLDKAAHETQFG 771 - 840 ...
Plasmid R777-E258 Hs.RASSF3-nostop from Dr. Dominic Espositos lab contains the insert RASSF3. This plasmid is available through Addgene.
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Fingerprint Dive into the research topics of MPP,sup,+,/sup,-induced neuronal death in rats involves tyrosine 33 phosphorylation of WW domain-containing oxidoreductase WOX1. Together they form a unique fingerprint. ...
The tumor suppressor protein promyelocytic leukemia protein (PML) was originally identified in acute promyelocytic leukemia because of a chromosomal translocation between chromosomes 15 and 17. arrest apoptosis senescence transcriptional regulation DNA repair and intermediary metabolism. TSU-68 Importantly PML inactivation in cancer cells can occur at the transcriptional- translational- or post-translational- levels. However only a few somatic mutations TSU-68 have been found in cancer cells. A better understanding of its regulation and its role in tumor suppression will provide potential therapeutic opportunities. In this review we discuss the function of PML in multiple tumor suppression pathways and summarize the players and stimuli that control PML proteins appearance or subcellular distribution. gene contains 9 exons and spans 53 approximately?kb in the genome. Because of substitute splicing of its C-terminal exons six nuclear and one cytoplasmic isoform have already been experimentally ...
The retinoblastoma (RB) and cyclin-dependent kinase inhibitor 2/multiple tumor suppressor gene 1 (CDKN2/MTS1) tumor suppressor genes play important roles in the regulation of the cell cycle. The protein products of these two genes, pRB and p16INK4A (p16), respectively, inhibit progression from G1 to S phase. Moreover, p16 has been shown to exert its function through inhibition of CDK4-mediated phosphorylation of pRB. Both genes have been found to be mutated or deleted in a wide range of primary human tumors and tumor cell lines. However, the presence of CDKN2/MTS1 containing nonneoplastic elements in every tumor specimen may contribute to the apparent lower deletion detection rate in resected neoplasms compared to cell lines. We have developed an immunohistochemical assay that allows us to assess p16 expression in formalin-fixed, paraffin-embedded tissues. As controls, we used paraffin-embedded pellets of cell lines with well-defined p16 status (four positive and four negative lines), as well ...
The Inhibitor of Growth 1 (ING1) gene has been identified and characterized as a Type-II tumor suppressor gene (TSG). Subsequently, 4 additional members of the family were identified by homology search. ING proteins contain a nuclear localization sequence (NLS) and a plant homeo domain (PHD) finger motif in their C-terminus. These proteins are involved in numerous signaling pathways especially in 2 tumor suppressor pathways: apoptosis and senescence. In human tumors, several studies have shown that the expression of ING1 is frequently lost or downregulated. It occurs most frequently at the RNA level, and thus epigenetics mechanism could be involved. We summarize the current knowledge on ING proteins functions and their involvement in various signaling pathways. We also review the studies that have investigated the ING protein status in human tumors. The interest of ING proteins as biomarkers and their role in tumor initiation and progression is discussed.
Canonical Wnt signaling is mediated by a molecular switch that regulates the transcriptional properties of the T-cell factor (TCF) family of DNA-binding proteins. Members of the myeloid translocation gene (MTG) family of transcriptional corepressors are frequently disrupted by chromosomal translocations in acute myeloid leukemia, whereas MTG16 may be inactivated in up to 40% of breast cancer and MTG8 is a candidate cancer gene in colorectal carcinoma. Genetic studies imply that this corepressor family may function in stem cells. Given that mice lacking Myeloid Translocation Gene Related-1 (Mtgr1) fail to maintain the secretory lineage in the small intestine, we surveyed transcription factors that might recruit Mtgr1 in intestinal stem cells or progenitor cells and found that MTG family members associate specifically with TCF4. Coexpression of beta-catenin disrupted the association between these corepressors and TCF4. Furthermore, when expressed in Xenopus embryos, MTG family members inhibited ...
A number of studies in lung cancer have shown that adjustments in the architecture of our DNA can result in chemo-resistance. Inactivation of RAS association domain family gene 2 (RASSF2; K-RAS adaptor protein) most commonly through promoter methylation, can confer a growth advantage in cancer cells having a K-RAS mutation. Both of these changes are common in lung cancer. Clark J et al. have determined that RASSF2 down regulation plays a role in cisplatin resistance [1]. Promoter hypermethylation of IGFBP-3 also encourages cisplatin resistance and it has been demonstrated that the basal methylation status of this gene may perhaps serve as a predictor to chemotherapy outcome [2]. In-depth promoter methylation analysis in the non-small cell lung cancer cell line A549, established significant differences in methylation patterns between its cisplatin resistant and sensitive subtypes. Significantly hypermethylated genes included G protein-coupled receptor 56 isoform 3 (GPR56), metallothionein 1G ...
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7-34 2. Chen H, Li N, Ren J, Feng X, Lyu Z, Wei L. et al. Participation and yield of a population-based colorectal cancer screening programme in China. Gut. 2019;68:1450-7 3. Pollard TD, Cooper JA. Actin, a central player in cell shape and movement. Science. 2009;326:1208-12 4. Bae DH, Jansson PJ, Huang ML, Kovacevic Z, Kalinowski D, Lee CS. et al. The role of NDRG1 in the pathology and potential treatment of human cancers. J Clin Pathol. 2013;66:911-7 5. Chen ZQ, Zhang DH, Yue F, Zheng MH, Kovacevic Z, Richardson DR. The Iron Chelators Dp44mT and DFO Inhibit TGF-beta-induced Epithelial-Mesenchymal Transition via Up-Regulation of N-Myc Downstream-regulated Gene 1 (NDRG1). Journal of Biological Chemistry. 2012;287:17016-28 6. Sahni S, Bae DH, Lane DJR, Kovacevic Z, Kalinowski DS, Jansson PJ. et al. The Metastasis Suppressor, N-myc Downstream-regulated Gene 1 (NDRG1), Inhibits Stress-induced Autophagy in Cancer ...
Oncogenic signaling pathways in cellular transformation and apoptosis Carcinogenesis is a multi-step process that involves activation of proto-oncogenes and inactivation of tumor suppressor genes. Gain-of-function mutations in oncogenes are frequently detected in human cancers. Activation of oncogenes plays an important role in cancer development and in altering cellular sensitivities to anti-cancer agents. Research in my laboratory focuses on a number of areas: (1) Cellular kinases signaling in cancer cell proliferation, survival and death; (2) Studying the function and regulation of tumor suppressor RASSF1A; (3) Investigating the role of a novel family of GTPases, RBEL1A, B, C and D in regulation of cell death and proliferation; (4) Investigating the role of a novel growth suppresive lipase in cell growth control and cancer development; (5) Identification and development of novel anticancer agents using traditional Chinese medicines.. SELECTED PUBLICATIONS: Meltzer, S. J., Yin, J., Huang, Y., ...
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). TheTSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified inTSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor. ...
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). TheTSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified inTSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.. ...
Full Text - CYLD is a deubiquitinating enzyme known for its role as a tumor suppressor whose mutation leads to skin appendages tumors and other cancers. In this manuscript we report that the tumor suppressor CYLD, similarly to other renowned tumor suppressor genes, protects from premature aging and cancer. We have generated transgenic mice expressing the mutant CYLDC/S protein, lacking its deubiquitinase function, under the control of the keratin 5 promoter, the K5-CYLDC/S mice. These mice express the transgene in different organs, including those considered to be more susceptible to aging, such as skin and thymus. Our results show that K5-CYLDC/S mice exhibit epidermal, hair follicle, and sebaceous gland alterations; and, importantly, they show signs of premature aging from an early age. Typically, 3-month-old K5-CYLDC/S mice exhibit a phenotype characterized by alopecia and kyphosis, and, the histological examination reveals that transgenic mice show signs
The mTOR/S6K/4E-BP1 pathway integrates extracellular signals derived from growth factors, and intracellular signals, determined by the availability of nutrients like amino acids and glucose. Activation of this pathway requires inhibition of the tumor suppressor complex TSC1/2. TSC2 is a GTPase-activ …
Qiu, G.-H.,Lim, C.Y.,Tao, Q.,Tan, L.K.S.,Loh, K.S.,Srivastava, G.,Tsai, S.-T.,Tsao, S.W. (2004). The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma. Oncogene 23 (27) : 4793-4806. [email protected] Repository. https://doi.org/10.1038/sj.onc.1207632 ...
Deleted in malignant brain tumours 1 (DMBT1), a candidate tumour suppressor gene located on chromosome 10q25.3-q26.1, has recently been identified and found to be deleted in several different types of human tumours. In melanomas, the chromosomal regi
Our and others previous reports have demonstrated that the tumor suppressor DLEC1 is able to suppress cancer cell growth in vitro and in vivo (2, 6). The present study further confirmed the cell suppression function of DLEC1 by inducing G1 arrest and apoptosis in DLEC1 stable clones in colorectal cancer cell line HCT116. Induction of G1 arrest is a complex process, involving numerous factors. In addition to those tested in our study, others, such as p27 and pRb, also regulate G1/S transition (34). In this study, we found that over-expression of DLEC1 stimulated the expression of AP-2α2 (Figure 4), another tumor suppressor known to induce cell cycle arrest at G1 and apoptosis in various cancers (19-21). Therefore, cancer cell suppression by DLEC1 may be mediated through up-regulation of AP-2α2.. Nevertheless, given that DLEC1 is unlikely to be a transcription factor (Figure 1), and that AP-2α2 was up-regulated at transcriptional level by DLEC1 over-expression (Figure 4), DLEC1 is not likely ...
Gene silencing suppressor 2b complexed with silencing RNA (ribonucleic acid). Computer model showing the structure of the gene silencing suppressor 2b (purple, green) complexed with synthetic silencing RNA (yellow, magenta). From Tomato aspermy virus. - Stock Image C035/8421
Oncogenes and tumor suppressor genes (TSGs) both play a role in oncogenesis via opposite mechanisms. Proto-oncogenes promote normal cell growth. Occasionally, a mutation increases their activity or a duplication, translocation, or other genetic event increases their expression. Under such conditions, these genes, now called oncogenes, cause abnormal unchecked cell growth. Examples of proto-oncogenes include growth factors, tyrosine kinases, regulatory GTPases, and transcription factors. TSGs inhibit cell growth in normal cells. However, decreases in TSG activity, often caused by mutation or promoter hypermethylation, prevents their ability to stop abnormal cell growth. Examples of TSGs include genes that regulate apoptosis, cell adhesion, or DNA damage signaling. Genes may have oncogenic properties, tumor suppressor properties, or both. These properties depend not only on the tumor type, but also on the known or observed differences in gene expression or epigenetic marks. Genetic differences in ...
In most myeloid leukemias induced in mice by γ-radiation, one copy of chromosome 2 has suffered a deletion. To search for a potential tumor suppressor gene in that region, we have delineated the deletions in a panel of these tumors. A commonly deleted region of 2 megabase pairs (Mbp) includes the gene encoding the PU.1 transcription factor, a powerful inducer of granulocytic/monocytic differentiation. Significantly, in 87% of these tumors the remaining PU.1 allele exhibited point mutations in the PU.1 DNA binding domain. Surprisingly, 86% of these mutations altered a single CpG, implicating deamination of deoxycytidine, a common mutational mechanism, as the origin of this lesion. The hot spot resides in the codon for a contact residue essential for DNA binding by PU.1. In keeping with a tumor suppressor role for PU.1, enforced expression of wild-type PU.1 in the promyelocytic leukemia cells inhibited their clonogenic growth, induced monocytic differentiation, and elicited apoptosis. The ...
The tuberous sclerosis 1 (TSC1) gene in humans encodes a peripheral membrane protein also known as hamartin, TSC, LAM, and KIAA0243. TSC1 complexes with TSC2 (tuberin) and stabilizes it. The TSC1/TSC2 complex inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (EIF4BP1) and ribosomal protein S6 kinase (S6K1), by negatively regulating signaling in the mammalian target of rapamycin complex 1 (mTORC1). Mutations in the TSC1 gene are associated with the development of tuberous sclerosis.. ...
The tuberous sclerosis 1 (TSC1) gene in humans encodes a peripheral membrane protein also known as hamartin, TSC, LAM, and KIAA0243. TSC1 complexes with TSC2 (tuberin) and stabilizes it. The TSC1/TSC2 complex inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 (EIF4BP1) and ribosomal protein S6 kinase (S6K1), by negatively regulating signaling in the mammalian target of rapamycin complex 1 (mTORC1). Mutations in the TSC1 gene are associated with the development of tuberous sclerosis.. ...
SnoN is a negative regulator of TGF-β signaling and also an activator of the tumor suppressor p53 in response to cellular stress. Its role in human cancer is complex and controversial with both pro-oncogenic and anti-oncogenic activities reported. To clarify its role in human cancer and provide clinical relevance to its signaling activities, we examined SnoN expression in normal and cancerous human esophageal, ovarian, pancreatic and breast tissues. In normal tissues, SnoN is expressed in both the epithelium and the surrounding stroma at a moderate level and is predominantly cytoplasmic. SnoN levels in all tumor epithelia examined are lower than or similar to that in the matched normal samples, consistent with its anti-tumorigenic activity in epithelial cells. In contrast, SnoN expression in the stroma is highly upregulated in the infiltrating inflammatory cells in high-grade esophageal and ovarian tumor samples, suggesting that SnoN may potentially promote malignant progression through ...
You have 2 copies of most genes - one from each parent. When someone has inherited an abnormal copy of a gene, their cells already start out with one mutation. If the other copy of the gene stops working (because of an acquired mutation, for example), the gene can stop functioning altogether. When the gene that stops working is a cancer susceptibility gene, cancer can develop. Some cancer susceptibility genes function as tumor suppressor genes. Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, or tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes dont work properly, cells can grow out of control, which can lead to cancer. Many family cancer syndromes are caused by inherited defects of tumor suppressor genes ...
FUNCTION: This gene encodes B cell translocation gene 3, a member of the BTG gene family. This family is defined by a conserved N-terminal domain, known to bind transcription factors, and a less conserved C-terminal domain. This protein is thought to have anti-proliferative properties, and may be involved in regulating the G1-S transition to suppress cell cycle progression. Mice deficient for this gene display an increased incidence of lung cancers, and many human lung cancer cells exhibit decreased levels of B cell translocation gene 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 17. [provided by RefSeq, Jul 2014 ...
LATS1 tumor suppressor is a serine/threonine kinase of the AGC kinase family and a core component of the Hippo pathway in mammals. LATS1 regulates various biological processes such as cell cycle progression, genetic stability, cell motility and adhesion, apoptosis, stem cell renewal and differentiation (Visser and Yang, 2010; Mo et al., 2014). LATS1 performs these functions by phosphorylating various substrates such as transcriptional co-activators YAP and TAZ (Zhao et al., 2007; Hao et al., 2008). LATS1 is also required for tissue homeostasis in both flies and mice (Visser et al., 2010). In addition to its roles in a broad spectrum of normal biological processes, loss of LATS1 has been shown to be important for the development of cancer and resistance to chemotherapeutic drugs (Visser et al., 2010). Therefore, understanding the molecular mechanisms underlying loss-of-LATS1-induced tumorigenesis and drug resistance will shed light on the design of new cancer treatment strategies in the future ...
The SEA/GATOR complex is an essential regulator of the mTORC1 pathway. In mammals the GATOR1 complex is composed of the proteins DEPDC5, NPRL2 and NPRL3. GATOR1 serves as an mTORC1 inhibitor and activates the mTORC1-modulating RagA GTPase. However, several GATOR members have mTORC1 independent functions. Here we characterize mammalian cells overexpressing the GATOR1 component NPRL2. We demonstrate that, in the cells with active p53, ectopic expression of NPRL2 induces NOX2-dependent production of reactive oxygen species and DNA damage. Overexpressed NPRL2 accumulates in the nucleus, together with apoptosis-inducing factor (AIF). These events are accompanied by phosphorylation of p53, activation of a DNA-damage response and cell cycle arrest in G1 phase, followed by apoptosis. In the cells negative for active p53, NPRL2 ectopic expression leads to activation of CHK1 or CHK2 kinases and cell cycle arrest in S or G2/M phases. Combined, these results demonstrate a new role for the NPRL2, distinct from its
References for Abcams Recombinant Human WWOX protein (ab86687). Please let us know if you have used this product in your publication
Lowe, S. (November 2002) Roles of oncogenes and tumor suppressor genes in apoptosis. European Journal of Cancer, 38. S15-S15. ISSN 0959-8049 ...
Checkpoint controls arrest the cell cycle after DNA damage, allowing repair to take place before mutations can be perpetuated. In multicellular organisms, DNA damage can also induce apoptotic cell death, protecting the organism at the expense of the individual cell. How does a cell choose between cycle arrest and death? Analysis of two human tumour suppressor proteins, p53 and the ATM (ataxia-telangiectasia mutated) gene product, may provide some answers.
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(2012) Gannon et al. Cancer Cell. DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in v...
Colorectal Cancer (CRC) is a genetic disease in which progression is driven by the accumulation of mutations or epigenetic alterations in oncogenes and tumor su...
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The Apoptotic Stimulating Proteins of p53 (ASPPs) are key regulators of the human tumour suppressor transcription factor, p53. These...
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no danger of their falling : Some names of things have an -ing form, though no -ed, and sometimes no -er form. Fall has only the -ing form. Drinking and running are two other examples used in this Step. Drink and run may, in addition, take -er. -- Take note that the person or thing in relation to which an -ing form is used, if not the same as the doer of the operation in the statement, has to be made clear by using an owner-form ...
us), National Center for Biotechnology Information (1998-01-01). The p53 tumor suppressor protein. National Center for ... These effects seem to be largely mediated by mutations at guanine in codon 249 of the p53 gene, a tumor suppressing gene, and ... liver tumors, especially given co-infection with hepatitis B virus. ...
Information (US), National Center for Biotechnology (1998). The p53 tumor suppressor protein. National Center for Biotechnology ... such as caspase proteins and Bcl-2 family regulation proteins. Before such process, the cell cycle withdrawal ensures that ... The CDK detects the presence of these cyclins by binding with these cyclins and produce a type of target protein to move the ... The first one is retinoblastoma protein, which prevents the cell from getting too large and to prohibit the premature ...
... tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53), is any isoform of a protein encoded by ... "The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and ... Tumor protein P53, also known as p53, cellular tumor antigen p53 (UniProt name), the Guardian of the Genome, phosphoprotein p53 ... National Center for Biotechnology Information (1998). The p53 tumor suppressor protein. Genes and Disease. United States ...
P53 The p53 tumor suppressor protein. National Center for Biotechnology Information (US). 1998. http://www.hsph.harvard.edu/ ... The p53 gene is known as the tumor suppressor gene. Molecular Epidemiology of Hereditary Cancers In his bio on the Harvard T.H ... These investigations have led to the identification and isolation of human cancer genes, the tumor suppressor genes. These ... The diversity of tumor types in this syndrome suggests pathogenetic mechanisms which differ from hereditary cancers arising in ...
His laboratory studies tumor suppressor proteins. In 2016, Kaelin received the Albert Lasker Award for Basic Medical Research ... Kaelin Jr on Nobelprize.org including the Nobel Lecture 7 December 2019 The von Hippel-Lindau Tumor Suppressor Protein: ... His major work has been on the retinoblastoma, von Hippel-Lindau, and p53 tumor suppressor genes. His work has been funded by ... His research at Dana-Farber has focused on understanding the role of mutations in tumor suppressor genes in cancer development ...
"Basal cell carcinoma tumor supressor (sic) gene". "Basal cell carcinoma tumor suppressor protein". http://www.erivedge.com/ ... a tumor suppressor gene that plays a critical role in the development of hereditary and sporadic basal cell cancer. He shares ... patents for the PTC gene and PTCH protein. In 2012, GenentechRoche introduced an oral medication based on the related hedgehog ...
p53 is a tumor suppressor protein. P53 may also refer to: p53 (band), an experimental music group p53 (album), a 1996 live ...
SIRT4 is a mitochondrial tumor suppressor protein. Overexpression of SIRT4 inhibits cancer cell proliferation by inhibition of ... SIRT4 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. SIRT4 exhibits NAD+- ... Frye RA (June 1999). "Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) ... Sirtuin 4, also known as SIRT4, is a mitochondrial protein which in humans is encoded by the SIRT4 gene. ...
Baas AF, Smit L, Clevers H (2004). "LKB1 tumor suppressor protein: PARtaker in cell polarity". Trends Cell Biol. 14 (6): 312-9 ... Protein kinase LYK5, also known as LYK5 or STRADα, is a human protein and also denotes the gene encoding it. Endogenous LKB1 ... "Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD". EMBO J. 22 (12): 3062-72. doi:10.1093/ ... "Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD". EMBO J. 22 (12): 3062-72. doi:10.1093/ ...
"Akt Phosphorylates and Regulates Pdcd4 Tumor Suppressor Protein". Cancer Research. 65 (24): 11282-6. doi:10.1158/0008-5472.CAN- ... Acts As a Tumor Suppressor in Neuroendocrine Tumor Cells". Annals of the New York Academy of Sciences. 1014: 220-1. doi:10.1196 ... Programmed cell death protein 4 is a protein that in humans is encoded by the PDCD4 gene. It is one of the targets of an ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
Sirt3 functions as a mitochondrial tumor suppressor protein. Although some evidence attributes SIRT3 activity in bypassing ... "SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during ... SIRT3 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. SIRT3 exhibits NAD+- ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-78. Bibcode:2005Natur. ...
... a novel serine/threonine protein kinase and potential tumour suppressor, is phosphorylated by cAMP-dependent protein kinase ( ... Baas AF, Smit L, Clevers H (June 2004). "LKB1 tumor suppressor protein: PARtaker in cell polarity". Trends in Cell Biology. 14 ... Yoo LI, Chung DC, Yuan J (July 2002). "LKB1--a master tumour suppressor of the small intestine and beyond". Nature Reviews. ... Katajisto P, Vallenius T, Vaahtomeri K, Ekman N, Udd L, Tiainen M, Mäkelä TP (January 2007). "The LKB1 tumor suppressor kinase ...
This protein may function as a tumor suppressor. CAV1 and CAV2 are located next to each other on chromosome 7 and express ... Caveolin-2 is a protein that in humans is encoded by the CAV2 gene. The protein encoded by this gene is a major component of ... 1995). "VIP21/caveolin is a cholesterol-binding protein". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10339-43. Bibcode:1995PNAS... ... Caveolin 2 has been shown to interact with Caveolin 1 and RAS p21 protein activator 1. GRCh38: Ensembl release 89: ...
HPV can induce tumor by several mechanisms: E6 and E7 oncogenic proteins. Disruption of tumor suppressor genes. High-level DNA ... Viral integration tends to occur in or near oncogenes or tumor suppressor genes and it is for this reason that the integration ... Gendicine is a gene therapy that employs an adenovirus to deliver the tumor suppressor gene p53 to cells. It was approved in ... The incidence of second primary tumors ranges in studies from 9% to 23% at 20 years. Second primary tumors are the major threat ...
... aggregation-prone mutants of the tumor-suppressor protein p53; and semen proteins whose aggregation enhances HIV infection. ... Examples include the proteins involved in Alzheimer's disease - amyloid β-protein (Aβ) and tau; α-synuclein, which is thought ... Amyloid β-protein Assembly: The Effect of Molecular Tweezer CLR01 and CLR03. J. Phys. Chem. B, 2015; 119: 4831-4841. S ... T Schrader, G Bitan, and F-G Klärner, Molecular Tweezers for Lysine and Arginine - Powerful Inhibitors of Pathologic Protein ...
Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors. The protein made by the ... tumor suppressor protein interacts with the APC protein". Oncogene. 14 (20): 2425-33. doi:10.1038/sj.onc.1201087. PMID 9188857 ... Su LK, Vogelstein B, Kinzler KW (December 1993). "Association of the APC tumor suppressor protein with catenins". Science. 262 ... of the tumor suppressor protein adenomatous polyposis coli (APC). Its structure and its interaction with chromosome maintenance ...
Su LK, Vogelstein B, Kinzler KW (December 1993). "Association of the APC tumor suppressor protein with catenins". Science. 262 ... "cancer is caused by sequential mutations of specific oncogenes and tumor suppressor genes". The first tumor suppressor gene ... discovered another tumor suppressor gene. This gene, called APC, was responsible for Familial Adenomatous Polyposis (FAP), a ... was thought to be an oncogene rather than a tumor suppressor gene. In 1989, Vogelstein and his students discovered that TP53 ...
... which controls both the levels of mRNA and overall protein levels. Point mutations in multiple tumor suppressor proteins cause ... The new protein is called a protein variant. If the original protein functions in cellular reproduction then this single point ... how do missense mutations in the tumor suppressor protein APC lead to cancer?". Mol. Cancer. 10: 101. doi:10.1186/1476-4598-10- ... protein localization, stability of the protein or protein complex. Many methods have been proposed to predict the effects of ...
Su LK, Vogelstein B, Kinzler KW (1993). "Association of the APC tumor suppressor protein with catenins". Science. 262 (5140): ... Poole AJ, Heap D, Carroll RE, Tyner AL (2004). "Tumor suppressor functions for the Cdk inhibitor p21 in the mouse colon". ... Thus, 8-OH-dG was increased, DNA repair protein ERCC1 was decreased, autophagy protein beclin-1 was increased and, in the stem ... "AOM-induced mouse colon tumors do not express full-length APC protein". Carcinogenesis. 18 (12): 2435-9. doi:10.1093/carcin/ ...
The key target of Mdm2 is the p53 tumor suppressor. Mdm2 has been identified as a p53 interacting protein that represses p53 ... Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that ... The E3 ubiquitin ligase MDM2 is a negative regulator of the p53 tumor suppressor protein. MDM2 binds and ubiquitinates p53, ... Momand J, Wu HH, Dasgupta G (January 2000). "MDM2--master regulator of the p53 tumor suppressor protein". Gene. 242 (1-2): 15- ...
Su LK, Vogelstein B, Kinzler KW (December 1993). "Association of the APC tumor suppressor protein with catenins". Science. 262 ... how do missense mutations in the tumor suppressor protein APC lead to cancer?" (PDF). Molecular Cancer. 10 (1): 101. doi: ... DIX domains are unique: the only other proteins known to have a DIX domain are Dishevelled and DIXDC1. (The single Dsh protein ... In Drosophila, the homologous protein is called armadillo. β-catenin is a subunit of the cadherin protein complex and acts as ...
Su LK, Vogelstein B, Kinzler KW (December 1993). "Association of the APC tumor suppressor protein with catenins". Science. 262 ... Su LK, Vogelstein B, Kinzler KW (1994). "Association of the APC tumor suppressor protein with catenins". Science. 262 (5140): ... αE-catenin also plays a role in tumor metastasis and skin cell function. Human αE-catenin protein is 100.0 kDa and 906 amino ... Oneyama C, Nakano H, Sharma SV (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction ...
The p53 gene codes for the tumor suppressor p53 proteins. A mutation in this gene can lead to formation of tumors. Five p53 ... In one study, out of 171 workers in a plant manufacturing 4-aminobiphenyl, 11% of them developed bladder tumors. Tumors ... A linear correlation was found between adduct levels and the occurrence of liver tumors in female mice by comparing DNA adducts ... compound can be metabolized by humans which the product may form adducts with DNA in human urothelial mucosa and bladder tumor ...
A similar protein in fly functions as a tumor suppressor. GRCh38: Ensembl release 89: ENSG00000165525 - Ensembl, May 2017 ... Nuclear export mediator factor (NEMF) is a protein that in humans is encoded by the NEMF gene. This gene encodes a component of ... The encoded protein facilitates the recognition and ubiquitination of stalled 60S subunits by the ubiquitin ligase listerin. ...
Kibel A, Iliopoulos O, DeCaprio JA, Kaelin WG (1995). "Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B ... "Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex". Proc. Natl ... The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. TCEB1 ... "Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein". J. ...
"Determinants of the tumor suppressor INPP4B protein and lipid phosphatase activities". Biochemical and Biophysical Research ... "Determinants of the tumor suppressor INPP4B protein and lipid phosphatase activities". Biochemical and Biophysical Research ... "Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling". Cancer Cell. 16 ... "Decreased expression and androgen regulation of the tumor suppressor gene INPP4B in prostate cancer". Cancer Research. 71 (2): ...
This gene encodes a protein that binds to matrix attachment regions. The protein functions as a tumor suppressor and cell cycle ... Protein BANP is a protein that in humans is encoded by the BANP gene. It is a member of the human gene family, "BEN-domain ... Jalota A, Singh K, Pavithra L, Kaul-Ghanekar R, Jameel S, Chattopadhyay S (Apr 2005). "Tumor suppressor SMAR1 activates and ... Rampalli S, Pavithra L, Bhatt A, Kundu TK, Chattopadhyay S (Oct 2005). "Tumor suppressor SMAR1 mediates cyclin D1 repression by ...
This limit can be overcome by disabling their pRB and p53 tumor suppressor proteins, which allows them to continue doubling ... These processes are orchestrated by proteins known as tumor suppressor genes. These genes take information from the cell to ... these tumour suppressor proteins are altered so that they don't effectively prevent cell division, even when the cell has ... A critical protein must malfunction in each of those mechanisms. These proteins become non-functional or malfunctioning when ...
Tumor suppressor protein 53 (p53) is mutated early in the disease. p53 is the "guardian of the genome", which, during DNA and ... Typically, any tumour presenting as above WHO grade I (i.e. a malignant tumour as opposed to a benign tumour) will have a ... Glioma at the Human Protein Atlas American Brain Tumor Association: Malignant Gliomas Brain and Spinal Tumors: Hope Through ... Often, tumor growth causes a breakdown of the blood-brain barrier in the vicinity of the tumor. As a rule, high-grade gliomas ...
Thompson TC (July 2010). "Glioma pathogenesis-related protein 1: tumor-suppressor activities and therapeutic potential". Yonsei ... Glioma pathogenesis-related protein 1 is a protein that in humans is encoded by the GLIPR1 gene. This gene encodes a protein ... p53, the tumor suppressor gene is the most commonly mutated gene in human cancer. Mutation in p53 gene can lead to cellular ... The previous finding of RTVP1 (GLIPR1) as a p53 target gene with tumor suppressor functions prompted the researches to initiate ...
... tumor-suppressor gene)的過度表現[14]。 ... non-protein-coding genes, and chromosomal structural elements) ... This proportion is much higher than can be explained by protein-coding sequences alone, implying that the genome contains many ...
In normal cells, α-catenin may act as a tumor suppressor and can help prevent the adhesion defects associated with cancer. On ... Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells. The first two ... a tumor suppressor gene product), CSNK1A1, and GSK3B. Following phosphorylation of the N-terminal Ser and Thr residues of β- ... "α-catenin is a tumor suppressor that controls cell accumulation by regulating the localization and activity of the ...
Over 90% of thyroid tumors arise from follicular thyroid cells.[8] A fusion protein, PAX8-PPAR-γ, is implicated in some ... Several known tumor suppressor genes like TP53 and WT1 have been identified as transcriptional targets in human astrocytoma ... The PAX genes give instructions for making proteins that attach themselves to certain areas of DNA.[6] This nuclear protein is ... These mutations can affect different functions of the protein including DNA biding, gene activation, protein stability, and ...
... which may function as a tumor-suppressor gene. The encoded protein is a type 1A regulatory subunit of protein kinase A. ... diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may ... The American neurosurgeon Harvey Cushing in 1914 reported a patient with a pituitary tumour that he had operated on. Post ... transition in the second codon position of the 74th codon in the protein) mutation in the PRKAR1A gene confirming the diagnosis ...
This gene is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor. By inducing G ( ... This process increases transcription of certain genes, notably CYP1A1, followed by increased CYP1A1 protein production.[28] ... and its carcinogenicity was demonstrated when skin tumors occurred in laboratory animals repeatedly painted with coal tar.[8] ... pyrene diol epoxide inactivates the tumor suppression ability in certain cells, leading to cancer. ...
Welch C, Chen Y, Stallings RL (2007). "MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in ... protein C-terminus binding. • protein binding. • four-way junction DNA binding. • identical protein binding. • ... This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2[10] and RAD52. ... Protein domains in homologous recombination-related proteins are conserved across the three main groups of life: archaea, ...
TNRC6A: encoding protein Trinucleotide repeat-containing gene 6A protein. *Tuberous sclerosis complex tumor suppressors: ... UNKL: encoding protein RING finger protein unkempt-like. *VAT1L: encoding protein Vesicle amine transport protein 1 homolog (T ... LINC00273 encoding protein Long intergenic non-protein coding RNA 273. *LOC124220: encoding protein Zymogen granule protein 16 ... SHCBP1: encoding protein SHC SH2 domain-binding protein 1. *SLZ1: encoding protein SLX1 structure-specific endonuclease subunit ...
In 1988 Ed Harlow demonstrates that cancer-causing and cancer-preventing genes (oncogenes and tumor-suppressor genes) interact; ... A.D. Hershey and Martha Chase, "Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage," J. General ... In 2011, Wigler, James Hicks and Nick Navin perform the first genomic profile of single cancer cells from a patient's tumor;[42 ... Upon taking charge in 1968, he focused the Laboratory on cancer research, creating a tumor virus group and successfully ...
1997). "Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor". Cancer Res. 57 (19): 4177-82. PMID ... 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor ... "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis ... 1998). "Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene ...
T cells (T lymphocytes) - T lymphocyte proliferation assay - T lymphocytes - T suppressor cells - T4 cell - T4 cells (T-helper ... proteins - protocol - protozoa - provirus - pruritus - pseudo-Cushing's syndrome - pseudovirion - PUBMED - pulmonary - purified ... tumor necrosis factor (TNF) ... helper/suppressor ratio (of T cells) - hematocrit - hematotoxic ... suppressor T cell - surrogate marker - surveillance - susceptible - symptoms - syncytium - syndrome - synergy - synergistic - ...
CD8+ cytotoxic T cells: virus-infected and tumor cells.. *γδ T cells: bridge between innate and adaptive immune responses; ... Regulatory (suppressor) T cells: Returns the functioning of the immune system to normal operation after infection; prevents ... It also makes blood vessels more permeable so neutrophils and clotting proteins can get into connective tissue more easily. ... Natural killer cells: virus-infected and tumor cells.. Deeply staining, eccentric. NK-cells and cytotoxic (CD8+) T-cells. Years ...
... pathway leads to stabilization of β-catenin through inactivation of a protein complex containing the tumor suppressors APC and ... Tumor development is a complex process that requires cell division, growth, and survival. One approach used by tumors to ... Another group found that high serum levels of IL-6 correlated with poor outcome in breast cancer tumors. Their research showed ... Moreover, it was shown that tumor progression selects for cells that are VEGF-dependent, challenging the belief that VEGF's ...
"Human MutS homologue MSH4 physically interacts with von Hippel-Lindau tumor suppressor-binding protein 1". Cancer Research 63 ( ... "Human MutS homologue MSH4 physically interacts with von Hippel-Lindau tumor suppressor-binding protein 1". Cancer Research 63 ( ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173-8. PMID 16189514. doi: ... prevalence in humans and effects on protein interaction". Biochemical and Biophysical Research Communications 332 (2): 524-32. ...
... and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The ... The protein degradation processEdit. Ribbon diagram of ubiquitin, the highly conserved protein that serves as a molecular tag ... Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks ... Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ...
Tumor suppressor[edit]. Several experiments have been done with mice and varying Beclin1, a protein that regulates autophagy. ... Thus these experiments show autophagy's role as a tumor suppressor.[83]. Tumor cell survival[edit]. Alternatively, autophagy ... There is evidence that emphasizes the role of autophagy both as a tumor suppressor as well as a factor in tumor cell survival. ... WIPI2, a PtdIns(3)P binding protein of the WIPI (WD-repeat protein interacting with phosphoinositides) protein family, was ...
Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes. Ligand. Growth factors. ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... a b Proto-Oncogene+Proteins+c-sis at the US National Library of Medicine Medical Subject Headings (MeSH) ... Hannink M, Donoghue DJ (1989). "Structure and function of platelet-derived growth factor (PDGF) and related proteins". Biochim ...
"Genistein mediated histone acetylation and demethylation activates tumor suppressor genes in prostate cancer cells". Int. J. ... In general, proteins fold into discrete units that perform distinct cellular functions, but some proteins are also capable of ... The first way is post translational modification of the amino acids that make up histone proteins. Histone proteins are made up ... thereby reducing that protein's activity. In PSI+ cells, the loss of the Sup35 protein (which is involved in termination of ...
... in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein ... McClain WH (November 1993). "Rules that govern tRNA identity in protein synthesis". Journal of Molecular Biology. 234 (2): 257- ... For instance, one can start with the gene for a protein that binds a certain sequence of DNA, and, by directing an unnatural ... Both classes of aminoacyl-tRNA synthetases are multidomain proteins. In a typical scenario, an aaRS consists of a catalytic ...
Other tumor suppressor genes that are thought to play a role in prostate cancer include PTEN (gene) and KAI1. "Up to 70 percent ... The protein ZIP1 is responsible for the active transport of zinc into prostate cells. One of the zinc's important roles is to ... Tumor markers. Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin ... ZIP1 is now called a tumor suppressor gene product for the gene SLC39A1. The cause of the epigenetic silencing is unknown. ...
... a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein". The Journal of ... protein binding. • protein complex scaffold activity. • protein kinase binding. • L27 domain binding. • ligand-gated ion ... a mammalian homolog of the Drosophila discs large tumor suppressor protein". Proceedings of the National Academy of Sciences of ... the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1". Proceedings of the National Academy ...
Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes. Ligand. Growth factors. ... protein binding. • cyclin-dependent protein serine/threonine kinase inhibitor activity. • ubiquitin protein ligase binding. • ... cyclin-dependent protein serine/threonine kinase activity. • protein kinase inhibitor activity. • protein kinase binding. • ... This article is about the p21Cip1 protein. For the p21/ras protein, see Ras (protein). For other uses, see P21 (disambiguation) ...
Induction of autoantibodies against tyrosinase-related proteins following DNA vaccination: Unexpected reactivity to a protein ... Suppressor population or Regulatory T cell theory, wherein regulatory T-lymphocytes (commonly CD4+FoxP3+ cells, among others) ... have been shown to both stimulate immune response to tumors in mice and to regulate immune function, delaying or preventing the ... All that is required is that a B cell recognising antigen X endocytoses and processes a protein Y (normally =X) and presents it ...
"Protein Sci. 14 (12): 3039-47. doi:10.1110/ps.051604805. PMC 2253247. PMID 16322581.. ... Von Hippel-Lindau tumor suppressor. *UBE3A. *Mdm2. *Anaphase-promoting complex. *UBR1. *Glutathione synthetase ...
... are potential treatments for cancer through the ability to epigenetically restore normal expression of tumor suppressor genes, ... Protein binding. 92-94%. Metabolism. Hepatic (mostly CYP3A4-mediated). Biological half-life. 3 hours. ... Antitumor activities on experimental tumors in mice". J. Antibiot. 47 (3): 315-323. doi:10.7164/antibiotics.47.315. PMID ...
Haddad LA, Smith N, Bowser M, Niida Y, Murthy V, Gonzalez-Agosti C, Ramesh V (November 2002). "The TSC1 tumor suppressor ... protein C-terminus binding. • protein binding. • identical protein binding. • protein heterodimerization activity. • Ras guanyl ... Neurofilament light polypeptide (NFL), also known as neurofilament light chain, is a neurofilament protein that in humans is ... protein polymerization. • intermediate filament bundle assembly. • neuromuscular process controlling balance. • neurofilament ...
The antibody will be targeted at a preferentially expressed protein in the tumour cells (known as a tumor antigen) or on cells ... and tumor suppressor genes (genes that help to prevent cancer), which gives cancer cells their malignant characteristics, such ... Blood vessels in tumors are very different from those seen in normal tissues. As a tumor grows, tumor cells furthest away from ... Tumor lysis syndrome[edit]. In particularly large tumors and cancers with high white cell counts, such as lymphomas, teratomas ...
"Specific-site methylation of tumour suppressor ANKRD11 in breast cancer". Eur. J. Cancer. 48 (17): 3300-9. doi:10.1016/j.ejca. ... This locus encodes an ankyrin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of ... Ankyrin repeat domain 11 is a protein that in humans is encoded by the ANKRD11 gene.[5] ...
... is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer, in J. Biol. Chem., vol. 276, nº 48, novembre 2001 ... Rob M Ewing, Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, et al., Large-scale mapping of human protein-protein interactions ... Gazin C, Rigolet M, Briand JP, et al., Immunochemical detection of proteins related to the human c-myc exon 1, in EMBO J., vol ... Q Guo, Xie J, Dang C V, Liu E T, Bishop J M, Identification of a large Myc-binding protein that contains RCC1-like repeats (PDF ...
... a tumor suppressor, or in the p53 pathway, and gain of function mutations in the Ras proteins, or in other oncogenes. ... 2002), I.3. Proteins: The Shape and Structure of Proteins *^ Alberts et al. (2002), I.3. Proteins: Protein Function Archived 25 ... like the fibers formed by the protein collagen. Proteins can bind to other proteins and simple molecules, sometimes acting as ... A single nucleotide difference within DNA can cause a change in the amino acid sequence of a protein. Because protein ...
... "microRNAs as oncogenes and tumor suppressors". Developmental Biology. 302 (1): 1-12. doi:10.1016/j.ydbio.2006.08.028. PMID ... In fission yeast this complex contains argonaute, a chromodomain protein Chp1, and a protein called Tas3 of unknown function.[ ... This ancestral RNAi system probably contained at least one dicer-like protein, one argonaute, one PIWI protein, and an RNA- ... Left: A full-length argonaute protein from the archaea species Pyrococcus furiosus. Right: The PIWI domain of an argonaute ...
... is a tumor suppressor gene, i.e., its activity stops the formation of tumors. If a person inherits only one functional copy of ... In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a ... Mutant p53 can no longer bind DNA in an effective way, and as a consequence the p21 protein is not made available to act as the ... However, mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading ...
Accumulation of p53 tumor suppressor gene protein: An independent marker of prognosis in breast cancers. J Natl Cancer Inst. ... p53 Tumor Suppressor Gene Protein, Immunohistochemical, Paraffin Block. TEST: 481044 Test number copied ... Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J ... Alterations of the p53 tumor suppressor gene have been shown to serve as an independent prognostic marker in a wide variety of ...
Researchers have found that a previously uncharacterized tumor-suppressor protein plays an important role in the functioning of ... Tumor suppressor protein plays key role in suppressing infections. American Society for Biochemistry and Molecular Biology ... These types of evidence have led scientists to categorize Arl11 as a tumor-suppressor protein. But it was almost completely ... Researchers have found that a previously uncharacterized tumor-suppressor protein plays an important role in the functioning of ...
Turning on the tumor-suppressor protein PTEN in cancers may be possible, a new study finds. In lab studies, the natural ... tumor-suppressor proteins. As their name suggests, these proteins normally act to stop abnormal cell growth. But they can lose ... a way to turn on one of the tumor-suppressor proteins most commonly silenced in cancer, called PTEN. They also found a natural ... "Researchers Turn On PTEN Tumor-Suppressor Protein in Cancer Cells was originally published by the National Cancer Institute." ...
The p73 protein is a structural and functional homolog of the p53 tumor suppressor protein (12, 13). p73 not only recognizes ... Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. Rami I. Aqeilan, Yuri Pekarsky, Juan J. ... The WWOX gene is a recently cloned tumor suppressor gene that spans the FRA16D fragile region. Wwox protein contains two WW ... Our findings reveal a functional cross-talk between p73 and Wwox tumor suppressor protein. ...
It does this by reading a chemical message attached to another protein thats tightly intertwined with DNA, a team led by ... A tumor-suppressing protein acts as a dimmer switch to dial down gene expression. ... Tumor-suppressor connects with histone protein to hinder gene expression. University of Texas M. D. Anderson Cancer Center ... Tumor-suppressor connects with histone protein to hinder gene expression ZMYND11 reads methylated variant to thwart cancer; ...
... 04.05.2011. UT MD Anderson-led team finds evidence that WWP2 ... Their research suggests that the little-studied protein binds to the tumor-suppressing protein PTEN (phosphatase and tensin ... Biotechnology »Cancer »NEDD4-1 »NEDD4-like »PTEN »Protein »cell death »embryonic stem cell »tumor formation ... A protein known as WWP2 appears to play a key role in tumor survival, a research team headed by a scientist at The University ...
Functional association between Wwox tumor suppressor protein and p73, a p53 homolog.. Aqeilan RI1, Pekarsky Y, Herrero JJ, ... The WWOX gene is a recently cloned tumor suppressor gene that spans the FRA16D fragile region. Wwox protein contains two WW ... Our findings reveal a functional cross-talk between p73 and Wwox tumor suppressor protein. ... Functional association between Wwox tumor suppressor protein and p73, a p53 homolog ...
It has been implicated in transcriptional regulation by modulating protein-protein interactions with p53 tumor suppressor ... Interferon-inducible protein 16: insight into the interaction with tumor suppressor p53.. Liao JC1, Lam R, Brazda V, Duan S, ... Interferon-Inducible Protein 16: Insight into the Interaction with Tumor Suppressor p53 ... Interferon-Inducible Protein 16: Insight into the Interaction with Tumor Suppressor p53 ...
... promote progression through the G1 phase of the cell cycle by phosphorylating the retinoblastoma protein (RB). The activities ... Retinoblastoma-protein-dependent cell-cycle inhibition by the tumour suppressor p16 Nature. 1995 Jun 8;375(6531):503-6. doi: ... The frequent deletion or mutation of CDKN2 in tumour cells suggests that p16 acts as a tumour suppressor. We show that wild- ... type p16 arrests normal diploid cells in late G1, whereas a tumour-associated mutant of p16 does not. Significantly, the ...
The tumor suppressor protein pRb blocks ubiquitination and increases the half-life of E2F1. (A) The indicated pRb expression ... Regulation of E2F through ubiquitin-proteasome-dependent degradation: Stabilization by the pRB tumor suppressor protein. Miguel ... Inhibition of E2F1 Ubiquitination and Degradation by the Retinoblastoma Tumor Suppressor Protein, pRB.. A previous study ... Regulation of E2F through ubiquitin-proteasome-dependent degradation: Stabilization by the pRB tumor suppressor protein ...
Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of ... other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins. ... multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously ... Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth. Jaya Sangodkar, … , Michael Ohlmeyer, Goutham ...
A large number of alternative spliced transcripts are transcribed from the PML gene, resulting in a variety of PML proteins ... PML exerts this pleiotropic role through its functionally interaction and with a large number of key proteins involved in these ... Theory covering any of the biological aspects involving this intriguing protein with functions not yet completely resolved. ... protein is a tumor suppressor implicated in tumorigenesis in different tissues. PML is object of intense research on the basis ...
... tumour suppressor protein WT1 contains a transcriptional regulatory domain that can either activate or repress transcription ... Regulation of the Wilms tumour suppressor protein transcriptional activation domain Oncogene. 1999 Nov 11;18(47):6546-54. doi ... The Wilms tumour suppressor protein WT1 contains a transcriptional regulatory domain that can either activate or repress ... We find that a region within the domain of WT1 attributed to transcriptional repression is a potent suppressor of the ...
Laboratory studies of mice and human cells found that a protein called Metastasis suppressor 1 (Mtss1) is downregulated in ... MTSS1 Protein May Act As Tumor Suppressor, Downregulated in CML. @media screen and (max-width: 468px) { .video-detail .doc- ... "We demonstrate that Mtss1 functions as a tumor suppressor in CML, providing a rationale for enhancing Mtss1 expression in CML ... Laboratory studies of mice and human cells found that a protein called Metastasis suppressor 1 (Mtss1) is downregulated in ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex ... Germ line-specific tumor suppressor essential for oogenesis (PubMed:7601353). Controls the spatial pattern of translation of ... This protein in other organisms (by gene name): Q17339 - Caenorhabditis elegans 4 * O02540 - Caenorhabditis elegans no matching ... Protein disorder predictions are based on JRONN (Troshin, P. and Barton, G. J. unpublished), a Java implementation of RONN * ...
Protein Binding · Protein Conformation · Serine · Signal Transduction · Sulfhydryl Compounds · Time Factors · Tumor Suppressor ... Mitogen-Activated Protein Kinase 1 · Mitogen-Activated Protein Kinase 3 · Mitogen-Activated Protein Kinases · Molecular ... MIF-(50-65) and its variant bound to the MIF-binding protein JAB1 and enhanced cellular levels of p27Kip1. As the peptide and ... A Cys-Xaa-Xaa-Cys (CXXC)-based thiol-protein oxidoreductase activity of MIF is associated with certain biological functions. ...
Leucine zipper putative tumor suppressor 1Add BLAST. 595. Amino acid modifications. Feature key. Position(s). Description ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... Leucine zipper putative tumor suppressor 1. Alternative name(s):. F37/esophageal cancer-related gene-coding leucine-zipper ... May act as a tumor suppressor.3 Publications. ,p>Manually curated information for which there is published experimental ...
Leucine zipper putative tumor suppressor 3Curated. Alternative name(s):. ProSAP-interacting protein 1By similarity. Manual ... Leucine zipper putative tumor suppressor 3Add BLAST. 700. Amino acid modifications. Feature key. Position(s). Description ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes ...
Structure of the wilms tumor suppressor protein zinc finger domain bound to DNA. Stoll, R., Lee, B.M., Debler, E.W., Laity, J.H ... The zinc finger domain of the Wilms tumor suppressor protein (WT1) contains four canonical Cys(2)His(2) zinc fingers. WT1 binds ... The zinc finger domain of the Wilms tumor suppressor protein (WT1) contains four canonical Cys(2)His(2) zinc fingers. WT1 binds ... Structure of the Wilms Tumor Suppressor Protein Zinc Finger Domain Bound to DNA. *DOI: 10.2210/pdb2JP9/pdb ...
"Tumor Suppressor Protein p53" by people in Harvard Catalyst Profiles by year, and whether "Tumor Suppressor Protein p53" was a ... "Tumor Suppressor Protein p53" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Below are the most recent publications written about "Tumor Suppressor Protein p53" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Tumor Suppressor Protein p53". ...
Further reports about: , CD24 , breast cancer , breast cells , stem cells , tumor cells , tumor suppressor ... Results showed that tumor cells containing the protein carried anywhere from 10 to 17 times fewer breast stem cells, and tumors ... Lab cell study shows that HOXA5 protein acts as tumor suppressor in breast cancer. 20.05.2016 ... Similarly, patients with tumors containing low amounts of HOXA5 protein also had lower cancer relapse-free survival rates. ...
Molecular model of the tumour suppressor protein p53 (left and right) bound to a molecule of DNA (deoxyribonucleic acid, green ... Tumour suppressor protein. Molecular model of the tumour suppressor protein p53 (left and right) bound to a molecule of DNA ( ... The protein binds to specific sequences in the DNA and halts the cell cycle (the means by which cells replicate). If there is ...
... tumor suppressor gene product, merlin (schwannomin) forms an intramolecular association that is required for negative growth ... we propose a model for merlin folding critical to its ability to function as a tumor suppressor protein.. ... In an effort to develop a molecular model for merlin relevant to its tumor suppressor function, we further characterized merlin ... Membrane Proteins / genetics*. Microtubules / chemistry. Neurofibromatosis 2 / genetics*. Neurofibromin 2. Protein Structure, ...
Association of the APC tumor suppressor protein with catenins Message Subject. (Your Name) has forwarded a page to you from ... Two cellular proteins that associate with APC were identified by nucleotide sequence analysis and peptide mapping as the E- ... These results suggest an important link between tumor initiation and cell adhesion. ... cadherin-associated proteins alpha- and beta-catenin. A 27-residue fragment of APC containing a 15-amino acid repeat was ...
Protein p53 is an important checkpoint in the cell cycle, ensuring the integrity of DNA replication. ... Shown here are the DNA-binding regions of the p53 tumor suppressor protein, bound to DNA. ... Shown here are the DNA-binding regions of the p53 tumor suppressor protein, bound to DNA. Protein p53 is an important ...
Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1 Sharon Wong; Sharon Wong ... In conclusion, our results demonstrate that SIRT1 is an in vitro and in vivo deacetylase for the Rb tumour suppressor protein. ... Sharon Wong, Jason D. Weber; Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1. Biochem J 1 November 2007 ... lysine residues within Rb formed a domain similar to the SIRT1-targeted domain of the p53 tumour suppressor protein. Cultures ...
... non-protein coding)), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol. ... Home Genes Leukemias Solid Tumors Cancer-Prone Deep Insight Case Reports Journals Portal Teaching X Y 1 2 3 4 5 6 7 8 9 10 11 ... Home Genes Leukemias Solid Tumors Cancer-Prone Deep Insight Case Reports Journals Portal Teaching For comments and suggestions ...
Tumor suppressor protein kinase Chk2 is a mediator of anoikis of intestinal epithelial cells.. [Byong Hoon Yoo, Alexander ... Chk2 can kill cells by stabilizing p53 tumor suppressor protein or via p53-independent mechanisms, and we established that Chk2 ... Thus, oncogenic ras can prevent Chk2 from triggering anoikis even when levels of this protein kinase are elevated in cancer ... a pro-apoptotic protein kinase that has never been implicated in anoikis and has been thought to kill cells mainly under the ...
PTEN is best known as one of the most frequently altered tumor suppressor genes in human cancers, but loss of the protein has ... Researchers showed that the tumor suppressor protein PTEN is essential for proper functioning of regulatory T cells. This small ... Jude Childrens Research Hospital scientists have discovered that a protein widely known for suppressing tumor formation also ... "In humans we know that loss of PTEN leads to tumors. This study highlights another role and shows that PTEN is also crucial for ...
  • The Wilms' tumour suppressor protein WT1 contains a transcriptional regulatory domain that can either activate or repress transcription depending upon its cellular environment. (nih.gov)
  • The zinc finger domain of the Wilms tumor suppressor protein (WT1) contains four canonical Cys(2)His(2) zinc fingers. (rcsb.org)
  • Brown, K. W. The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42;p15) breakpoint associated with Wilms' tumour. (humpath.com)
  • Wilms' tumour is a paediatric malignancy of the kidneys and is the most common solid tumour found in children. (biochemsoctrans.org)
  • The Wilms' tumour suppressor protein WT1 is mutated in approx. (biochemsoctrans.org)
  • The Wilms' tumour suppressor protein WT1 is a transcriptional activator, the function of which is under cell-context-specific control. (biochemsoctrans.org)
  • The Wilms' tumour-suppressor gene ( WT1 ), encodes a zinc-finger transcription factor that is critical for the development of several organs, including the kidneys, gonads and spleen. (biochemsoctrans.org)
  • Despite its identification as a tumour suppressor that plays a crucial role in the formation of a paediatric malignancy of the kidneys (Wilms' tumour), it has also emerged as an oncogenic factor influencing proliferation and apoptosis in a large variety of adult cancers. (biochemsoctrans.org)
  • This study analyzed a potential regulation of nephrin by the Wilms' tumor protein, Wt1. (asnjournals.org)
  • The Wilms' tumor gene Wt1 encodes a zinc finger protein that has been identified on the basis of its involvement in nephroblastoma, an embryonic kidney tumor. (asnjournals.org)
  • Knockdown of PDCD4 by RNA interference (siRNA) inhibited ATRA-induced granulocytic differentiation and reduced expression of key proteins known to be regulated by ATRA, including p27 Kip1 and DAP5/p97, and induced c-myc and Wilms' tumor 1, but did not alter expression of c-jun, p21 Waf1/Cip1 , and tissue transglutaminase (TG2). (aacrjournals.org)
  • The Wilms' tumour' suppressor protein, WT1, is a zinc finger protein essential for the development of several organs, including the kidney and gonads. (umn.edu)
  • However, mutations in p53 are found in most tumor types, and so contribute to the complex network of molecular events leading to tumor formation. (lifeboat.com)
  • p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors. (uniprot.org)
  • Mutations in proteins localized to cilia have been implicated in a growing number of human diseases. (rupress.org)
  • This thesis presents the first report of the comprehensive and quantitative analysis of the effects of tumor-derived mutations on the tetrameric structure of tumor suppressor protein p53, which plays a central role in maintaining genomic integrity. (springer.com)
  • large rearrangements, deletions, and missense mutations in the BAP1 gene locus have been found in lung and sporadic breast tumors and lung cancer cell lines ( 3 , 11 ), and BAP1 suppresses growth of breast cancer cells in vitro ( 3 ). (aacrjournals.org)
  • Furthermore, it is unknown whether cancer-associated BAP1 mutations affect protein function. (aacrjournals.org)
  • In this study, we sought to characterize the in vivo growth suppression phenotype of BAP1, to determine if it was a genuine tumor suppressor, to ask whether the mutations found in cancer cells inactivated protein function, and to ask whether BAP1 exerted its tumor suppressor activity through the BRCA1 pathway. (aacrjournals.org)
  • More than half of human cancers involve mutations in the p53 tumor-sup. (bio-medicine.org)
  • More than half of human cancers involve mutations in the p53 tumor-suppressor gene, suggesting the critical role played by the normal p53 protein in defending against cancer. (bio-medicine.org)
  • Similarly, roughly 95 percent of cancer-causing mutations in the p53 protein occur in its DNA-binding core domain, pointing to this region of the p53 protein as being pivotal to its anti-cancer activity. (bio-medicine.org)
  • Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are linked to both familial and sporadic human colon cancer. (rupress.org)
  • Signaling activity resides in the central domain of the protein, a part of the molecule that is missing in most of the truncating APC mutations in colon cancer. (rupress.org)
  • von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome characterized by the development of renal carcinomas, pheochromocytomas, and vascular tumors of the central nervous system and retina, is caused by germ line mutations in the VHL tumor suppressor gene ( 9 , 17 , 27 , 35 ). (asm.org)
  • Germline mutations in the tumor-suppressor gene BRCA2 predispose to breast and ovarian cancer. (biologists.org)
  • Genetic mutations aren't the only thing that can keep a protein called PTEN from doing its tumor-suppressing job. (technologynetworks.com)
  • In addition to phosphate tags, mutations in genes that code for a protein can cause some protein activities to be permanently on or off. (technologynetworks.com)
  • So, increasing the activity of PTEN might be helpful not only to patients with defective PTEN, but also to those with cancer-causing mutations in other proteins. (technologynetworks.com)
  • Mutations of this tumor suppressor gene are the most frequently reported gene alteration in human cancers [26, 27]. (clicktocurecancer.info)
  • We demonstrate that Mtss1 functions as a tumor suppressor in CML, providing a rationale for enhancing Mtss1 expression in CML in order to target the TKI-resistant stem cell population," they authors concluded. (cancernetwork.com)
  • The WWOX gene encodes a 46-kDa protein that contains two WW domains and a short-chain dehydrogenase/reductase domain (SDR) ( 1 ). (pnas.org)
  • Common fragile site gene WWOX encodes a candidate tumor suppressor WW domain-containing oxidoreductase. (humpath.com)
  • Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) encodes the p110α subunit of the mitogenic signaling protein phosphoinositide 3-kinase (PI3K). (humpath.com)
  • This gene encodes the Drosophila homolog of human ribosomal protein S6. (biologists.org)
  • A gene on chromosome 13q14.2 that encodes a tumour suppressor related to the ADP-ribosylation factor (ARF) family of proteins, which may play a role in apoptosis in a caspase-dependent manner. (thefreedictionary.com)
  • Here we demonstrate that the new gene, referred to as 3pK (for chromosome 3p kinase), in fact encodes a mitogen-activated protein kinase-regulated protein serine-threonine kinase with a novel substrate specificity. (asm.org)
  • The APC gene encodes a 300-kD protein, consisting of 2,843 amino acids, which has several structural domains. (rupress.org)
  • NPHS1 encodes the structural protein nephrin, which has a crucial role in the filtration barrier of the glomerular podocyte. (asnjournals.org)
  • In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2). (lifeboat.com)
  • Shi and colleagues found that the protein ZMYND11 "reads" the modified histone H3.3 by connecting to it where a tri-methyl chemical group binds to H3.3. (eurekalert.org)
  • Their research suggests that the little-studied protein binds to the tumor-suppressing protein PTEN (phosphatase and tensin homologue deleted on chromosome 10), marking it for destruction by proteasomes, which degrade proteins and recycle their components. (innovations-report.com)
  • The protein binds to specific sequences in the DNA and halts the cell cycle (the means by which cells replicate). (sciencephoto.com)
  • This naturally occurring form contains a pairing of two p53 proteins, called a dimer, that then binds to a second p53 dimer in a similar way to create the precisely oriented four-protein complex, called a tetramer, that binds DNA. (bio-medicine.org)
  • We knew that the Fhit protein is an enzyme that binds and cleaves an unusual class of nucleotides in the cell, called ApppA," he explains. (bio-medicine.org)
  • The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O 2 ) conditions. (asm.org)
  • Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. (asm.org)
  • The APC tumor suppressor binds to C-terminal binding protein to divert nuclear beta-catenin from TCF. (ihop-net.org)
  • They also found that HOCA3 regulates the production of two other proteins, CD24 and E-cadherin, cells, without CD24, the cells begin to revert toward a stem like state, and without E-cadherin, cells lose some of the glue that binds them to other cells. (holistichealthshow.com)
  • The N-terminal region of the protein binds CDC2 to form a complex showing reduced H1 histone kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. (biomol.com)
  • The tumor suppressor p53 binding protein 1 (53BP1) binds to the DNA-binding domain of p53 and enhances p53-mediated transcriptional activation. (rupress.org)
  • For example, if a MAb binds to protein X with a Z-score of 43 and to protein Y with a Z-score of 14, then the S-score for the binding of that MAb to protein X is equal to 29. (neobiotechnologies.com)
  • It binds to MDM2, SV40 T antigen and human papilloma virus E6 protein. (neobiotechnologies.com)
  • A protein that helps to regulate the life cycle of cells appears to have a direct bearing on mesothelioma treatment response and survival. (survivingmesothelioma.com)
  • Addgene: Keratinization-associated miR-7 and miR-21 regulate tumor suppressor reversion-inducing cysteine-rich protein with kazal motifs (RECK) in oral cancer. (addgene.org)
  • Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway was found to regulate PDCD4 expression because inhibition of PI3K by LY294002 and wortmannin or of mTOR by rapamycin induced PDCD4 protein and mRNA expression. (aacrjournals.org)
  • The retinoblastoma tumour suppressor protein (pRb) classically functions to regulate early cell cycle progression where it acts to enforce a number of checkpoints in response to cellular stress and DNA damage. (ox.ac.uk)
  • Yes-associated protein (YAP) has been shown to positively regulate p53 family members and to be negatively regulated by the AKT proto-oncogene product in promoting apoptosis. (icr.ac.uk)
  • This protein has been shown to up-regulate the transcription of the catalytic subunit of telomerase, hTERT. (biomedcentral.com)
  • This study, for the first time, identifies a novel role of a histone variant protein in regulating gene transcription aside from its established roles," said senior author Xiaobing Shi, Ph.D., assistant professor of Biochemistry and Molecular Biology at The University of Texas MD Anderson Cancer Center. (eurekalert.org)
  • A large number of alternative spliced transcripts are transcribed from the PML gene, resulting in a variety of PML proteins ranging in molecular weight. (frontiersin.org)
  • Molecular model of the tumour suppressor protein p53 (left and right) bound to a molecule of DNA (deoxyribonucleic acid, green and pink) at the p53 response element. (sciencephoto.com)
  • In an effort to develop a molecular model for merlin relevant to its tumor suppressor function, we further characterized merlin intramolecular folding. (biomedsearch.com)
  • Here we describe recent work on the molecular identification of tumor suppressor genes that function in two different cell types of the Drosophila larva: the blood cells, and the undifferentiated epithelial cells of developing imaginal discs. (biologists.org)
  • With state-of-the art molecular biology and protein biochemistry labs, we work with our clients to rapidly evaluate in parallel to identify the optimal expression system for candidate proteins. (abgent.com)
  • We are rapidly demystifying cancers, exposing the molecular mechanisms underlying tumors and leading the search for the next generation of targeted cancer therapies. (salk.edu)
  • We show that BAP1 exerts its tumor suppressor functions by affecting the cell cycle, speeding the progression through the G 1 -S checkpoint, and inducing cell death via a process that has characteristics of both apoptosis and necrosis. (aacrjournals.org)
  • Overexpression of MDA-7 via adenoviral vector (Ad-MDA7) infection induces apoptosis of a number of tumor cell types, but not normal cells, and in model tumor systems has led to suppressed growth and reduced metastasis ( 12 , 13 , 14 , 15 , 16 ). (jimmunol.org)
  • ATRA, a naturally occurring derivative of vitamin A (retinol), is a potent inducer of cellular differentiation, growth arrest, and apoptosis in various tumor cell lines. (aacrjournals.org)
  • Daxx is a scaffold protein with roles in diverse processes, including transcriptional regulation, DNA-damage signaling, apoptosis and chromatin remodeling. (le.ac.uk)
  • One key protein that coordinates DNA repair with cell cycle progression and apoptosis is the tumor suppressor protein p53. (rupress.org)
  • It is a tumor suppressor protein expressed in a wide variety of tissue types and is involved in regulating cell growth, replication, and apoptosis. (neobiotechnologies.com)
  • p53, a tumor suppressor protein has a prominent role in forestalling tumor development and advancement through its involvement in cell division control and initiation of apoptosis. (elsevier.com)
  • To see if WWP1 might be a weak link in this pathway between MYC and PTEN, researchers deleted the gene for WWP1 in mice that are genetically prone to developing prostate tumors. (cancer.gov)
  • They found that mice lacking WWP1 had far fewer and smaller prostate tumors than mice with the gene. (cancer.gov)
  • When they analyzed tissue samples taken from the mouse tumors, they found that more PTEN had been able to make its way to the surface of cells in tumors of the mice with the WWP1 deletion. (cancer.gov)
  • In contrast, less PTEN went to the surface of cells in tumors of mice with normal WWP1. (cancer.gov)
  • In a mouse model of triple-negative breast cancer, mice injected with cancer cells that over-express ZMYND11 had tumor volumes of less than 50 cubic millimeters while control mice and those injected with cells expressing ZMYND11 deficient for binding to the methyl group had tumor volumes ranging from 150 to 400 cubic millimeters at eight weeks. (eurekalert.org)
  • But when NEDD4-1 is deleted in mice, researchers have not seen a clear change in PTEN protein level," Chen noted. (innovations-report.com)
  • In one experiment, mice with normal WWP2 developed prostate cancer tumors after nine weeks that were more than three times the size of tumors in mice with WWP2 silenced. (innovations-report.com)
  • Evidence that this repression of cell proliferative genes is an important function of E2F in controlling cell growth is suggested from recent studies demonstrating that inactivation of E2F1 leads to increased cell proliferation and tumor formation in mice ( 10 , 11 ). (pnas.org)
  • Laboratory studies of mice and human cells found that a protein called Metastasis suppressor 1 (Mtss1) is downregulated in hematopoietic and progenitor cells when chronic myeloid leukemia is present. (cancernetwork.com)
  • The protein was totally absent in leukemic progenitor cells when mice were induced to express Bcr-Abl, while high Mtss1 expression levels were seen in three out of four control mice. (cancernetwork.com)
  • They then tested the behavior of human tumor cells with and without HOXA5 by injecting those cells into the mammary fat pad of mice. (innovations-report.com)
  • Results showed that tumor cells containing the protein carried anywhere from 10 to 17 times fewer breast stem cells, and tumors grown from the injected cells were about three times smaller than those in mice who had received tumor cells with depleted levels of HOXA5. (innovations-report.com)
  • In this study, we have shown for the first time that BAP1 has tumor suppressor activity in vivo by showing that BAP1 can suppress tumorigenicity of lung cancer cells in athymic nude mice. (aacrjournals.org)
  • Furthermore, we show that deubiquitinating activity and nuclear localization are both required for BAP1-mediated tumor suppression in nude mice. (aacrjournals.org)
  • We performed a genome-wide screen to identify suppressors of liver tumor formation in mice, using CRISPR-mediated genome editing. (mit.edu)
  • Within 1 month, all the mice that received the sgRNA library developed subcutaneous tumors. (mit.edu)
  • their expression was knocked down using small hairpin RNAs, and tumor growth was examined in nude mice. (mit.edu)
  • CRISPR-mediated knockout of Nf1, a negative regulator of RAS, accelerated liver tumor formation in mice. (mit.edu)
  • Liver cancer cells with inactivation of Plxnb1, Flrt2, and B9d1 formed more tumors in mice and had increased levels of mitogen-activated protein kinase phosphorylation. (mit.edu)
  • We validated the observation that RAS signaling, via mitogen-activated protein kinase, contributes to formation of liver tumors in mice. (mit.edu)
  • Consistent with this observation, we recently found that the two major podocyte proteins nephrin and podocalyxin were lowered in the kidneys of mice with reduced expression of Wt1 ( 13 ), suggesting co-regulation of nephrin and Wt1. (asnjournals.org)
  • After injecting human tumor cells with and without HOXA5 into the mammary fat pad of mice they found that tumor cells containing protein carried anywhere from 10 to 17 times fewer breast stem cells, and tumor growth from the injected cells were about 3 times smaller than those in mice who received tumor cells with depleted levels of HOXA5. (holistichealthshow.com)
  • This is supported by studies in knockout mice showing development of soft-tissue sarcomas, ovarian stromal cell tumors and a high sensitivity to carcinogenic treatments. (biomol.com)
  • In this study, high titer ANAs specific for the p53 tumor suppressor protein were induced in mice immunized with purified complexes of murine p53 and the Simian virus 40 large T antigen (SVT), but not in mice immunized with either protein separately. (rupress.org)
  • Functionally, short hairpin RNA knockdown of YAP in breast cell lines suppressed anoikis, increased migration and invasiveness, inhibited the response to taxol and enhanced tumor growth in nude mice. (icr.ac.uk)
  • Indeed, key regulators of the cell-cycle machinery, such as cyclins and cyclin-dependent kinase inhibitors, are short-lived proteins that are degraded through the ubiquitin-proteasome pathway ( 14 , 15 ). (pnas.org)
  • Tumor suppressor protein kinase Chk2 is a mediator of anoikis of intestinal epithelial cells. (sigmaaldrich.com)
  • In an effort to understand them we found that detachment of nonmalignant intestinal epithelial cells triggers upregulation of Chk2, a pro-apoptotic protein kinase that has never been implicated in anoikis and has been thought to kill cells mainly under the conditions compromising genome integrity. (sigmaaldrich.com)
  • Thus, oncogenic ras can prevent Chk2 from triggering anoikis even when levels of this protein kinase are elevated in cancer cells, and the use of therapeutic agents that kill cells in a Chk-2-independent, rather than Chk-2-dependent, manner could represent an efficient strategy for overcoming ras-induced anoikis resistance of these cells. (sigmaaldrich.com)
  • The dig protein product (DlgA) is localized at septate junctions between epithelial cells, and cDNA sequencing indicates that the gene product includes a domain with homology to guanylate kinase (GUK). (biologists.org)
  • In this report, we investigated the hypothesis that overexpression of the tumor suppressor protein PTEN, an inositol phosphatase specific for the products of PI 3-kinase, would inhibit the vascular smooth muscle cell (VSMC) responses necessary for neointimal hyperplasia and restenosis. (ahajournals.org)
  • 7 Similarly, phosphorylation by mTOR activates the p70 ribosomal protein S6 kinase (p70 s6k ), resulting in phosphorylation of the 40S ribosomal protein S6 and translation of key components of the cell's translational apparatus. (ahajournals.org)
  • 13 These processes are regulated in turn by several intermediate signaling proteins, including the 3-phosphoinositide-dependent kinase PDK1 and Akt, both of which are recruited to and associate with the plasma membrane-bound 3-phosphoinositides. (ahajournals.org)
  • 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region. (asm.org)
  • Computer analysis and a search of the GenBank database to reveal high sequence identity of the product of this gene to serine-threonine kinases, especially to mitogen-activated protein kinase-activated protein kinase 2, a recently described substrate of mitogen-activated kinases. (asm.org)
  • Sequence identitiy was 72% at the nucleotide level and 75% at the amino acid level, strongly suggesting that this protein is a serine-threonine kinase. (asm.org)
  • The phosphorylation pattern of p53 was analysed in normal or v-raf-transformed rat cells or in insect cells which were co-infected with recombinant baculoviruses encoding p53, protein kinase C and c-Raf. (spandidos-publications.com)
  • Furthermore, it was found that nephrin functions as a signaling molecule that can activate mitogen-activated protein kinase cascades ( 8 ). (asnjournals.org)
  • The protein encoded by this gene is a putative serine/threonine kinase that localizes to the. (biomol.com)
  • The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. (biomol.com)
  • Daxx has previously been shown to serve as a scaffold for protein kinase Hipk2 and tumor suppressor protein p53 and to stimulate the phosphorylation of p53 at serine 46 (Ser-46) in response to genotoxic stress. (le.ac.uk)
  • SSeCKS is a major protein kinase C substrate which has tumour suppressor activity in models of src- and ras-induced oncogenic transformation. (semanticscholar.org)
  • Interleukin-17F-induced pulmonary microvascular endothelial monolayer hyperpermeability via the protein kinase C pathway. (semanticscholar.org)
  • Involvement of the protein kinase C substrate, SSeCKS, in the actin-based stellate morphology of mesangial cells. (semanticscholar.org)
  • Activation of glomerular mesangial cells by hepatocyte growth factor through tyrosine kinase and protein kinase C. (semanticscholar.org)
  • The disruption of this E2F-Rb interaction, as well as a complex involving E2F in association with the cell cycle-regulated cyclin A-cdk2 kinase complex, may be a common mechanism of action for the oncoproteins encoded by the DNA tumor viruses. (sciencemag.org)
  • The timely degradation of certain transiently induced and/or oscillatory proteins is fundamentally linked to the regulation of such genes. (pnas.org)
  • The neurofibromatosis 2 (NF2) tumor suppressor gene product, merlin (schwannomin) forms an intramolecular association that is required for negative growth regulation in vitro and in vivo. (biomedsearch.com)
  • P16 plays an important role in cell cycle regulation, slowing down the progression of cells from the first phase, during which cells make mRNA and proteins, to the S1 phase during which DNA is replicated. (survivingmesothelioma.com)
  • Although we know that ZMYND11 controls RNA polymerase II travel ratio in the gene body, we still don't know how this protein, which does not physically interact with polymerase II, actually achieves this regulation," Shi said. (medicalxpress.com)
  • The retinoblastoma tumor suppressor protein pRb is a master regulator of cellular proliferation, principally through interaction with E2F and regulation of E2F target genes. (ox.ac.uk)
  • As these cells with limited functions are inefficient in performing body activities, they are programmed to self demolition under the presence of apoptotic signals, such as caspase proteins and Bcl-2 family regulation proteins. (wikipedia.org)
  • The PTEN protein works in different ways to suppress the formation and spread of tumors. (cancer.gov)
  • Researchers have now identified, in both human cancer cells and mouse models, a way to turn on one of the tumor-suppressor proteins most commonly silenced in cancer, called PTEN . (cancer.gov)
  • As a result, proteins that are normally kept in check by PTEN (a signaling pathway ) can become overly active and can drive uncontrolled cell growth, she said. (cancer.gov)
  • Looking for a better approach to reactivating PTEN in cancer cells, the study's lead investigator, Yu-Ru Lee, Ph.D., and his colleagues in the Pandolfi lab embarked on a 5-year search for other proteins that interact with PTEN. (cancer.gov)
  • They began by sifting through cancer cells looking for proteins that bind physically to PTEN. (cancer.gov)
  • PTEN can exert its tumor-suppressive functions only when it is located in the surface area of cells. (cancer.gov)
  • We were trying to find regulators of PTEN when we isolated the protein WWP2 as a putative PTEN-associated protein," Chen said. (innovations-report.com)
  • He noted that WWP2 caught the researchers' attention because it is similar to the NEDD4-1 protein, which has been proposed as a regulator of PTEN function. (innovations-report.com)
  • We need to look at real tumor samples to determine whether tumors with reduced PTEN expression could result from the overexpression of WWP2. (innovations-report.com)
  • He added that some early studies suggest that WWP2 may operate in tumors, but a correlation between WWP2 overexpression and PTEN downregulation in tumors has not been established. (innovations-report.com)
  • Researchers showed that the tumor suppressor protein PTEN is essential for proper functioning of regulatory T cells. (healthcanal.com)
  • PTEN is best known as one of the most frequently altered tumor suppressor genes in human cancers, but loss of the protein has also been tied to autoimmune problems. (healthcanal.com)
  • In humans we know that loss of PTEN leads to tumors. (healthcanal.com)
  • But there are times when a cell needs to divide to replace dead cells, so scientists knew there had to be a naturally occurring mechanism for turning PTEN off, and they hypothesized that the phosphates on its tail were responsible, as they are in other proteins. (technologynetworks.com)
  • Armed with their engineered protein, the team analyzed its shape, where in cells it was located and its activity - tasks aided by miniature X-ray imagers and biochemical tests that shed light on how PTEN interacted with other entities, like PIP3, a fat-like molecule located just inside the outer envelope of cells. (technologynetworks.com)
  • Its tail curls back on the rest of the protein and prevents it from interacting with PIP3 in the outer envelope of the cell, so PTEN ends up inactive, in the fluid-filled middle of the cell. (technologynetworks.com)
  • When the phosphates are removed, PTEN relocates to the outer envelope, where it removes a phosphate tag from PIP3 to initiate the chain reaction that suppresses tumor formation. (technologynetworks.com)
  • Any drug that can prevent the tail from binding itself might also maintain the tumor-fighting activity of PTEN. (technologynetworks.com)
  • According to Cole, many cancer patients have an overabundance of CK2, the protein that adds phosphates to PTEN and turns it off. (technologynetworks.com)
  • In this study, we demonstrate that the von Hippel-Lindau (VHL) protein (pVHL) is a ciliary protein that controls ciliogenesis in kidney cells. (rupress.org)
  • The tumor syndrome von Hippel-Lindau (VHL) disease is caused by heterozygous germline inactivation of the VHL tumor suppressor gene, which resides on chromosome 3p25 ( Kaelin, 2003 ). (rupress.org)
  • In budding yeast, the von Hippel Lindau protein (pVHL) is misfolded and forms aggregates. (biologists.org)
  • Previous studies identified an overlapping region of E2F1 that facilitates complex formation with retinoblastoma tumor suppressor protein, pRB, and we found that pRB blocks ubiquitination and stabilizes E2F1. (pnas.org)
  • NotI linking clones, localized to the human chromosome 3p21.3 region and homozygously deleted in small cell lung cancer cell lines NCI-H740 and NCI-H1450, were used to search for a putative tumor suppressor gene(s). (asm.org)
  • A defined chromosome 6q fragment (at D6S310) harbors a putative tumor suppressor gene for breast cancer. (semanticscholar.org)
  • p16INK4a is part of a cell-cycle regulatory pathway that converges in the tumor suppressor protein Rb. (nih.gov)
  • Here we provide evidence that E2F1 protein levels are regulated by the ubiquitin-proteasome-dependent degradation pathway. (pnas.org)
  • This is the mTOR pathway, in which the protein complexes mTORC1 and mTORC2 play central roles. (healthcanal.com)
  • Tsc1 is best known as a tumor suppressor, helping to prevent cancer development by inhibiting activity of the mTOR protein and the pathway that bears its name. (healthcanal.com)
  • In this study, scientists showed that loss of the Tsc1 protein predisposed affected T cells to premature activation, resulting in programmed cell death via the cell's suicide pathway. (healthcanal.com)
  • Tumor-suppressor genes help prevent uncontrolled cell growth Tumor-suppressor Proteins: Repair of damaged DNA, control cell adhesion and inhibit the cell cycle in the signaling pathway Ras proto-oncogen p53 tumor-suppressor gene Multistep Model 1 active oncogene mutation in several tumor-suppressor genes Malignant cancerous, metastasis cancer cells move to a new location. (coursehero.com)
  • The p53 tumor suppressor protein plays a crucial role in influencing cell survival in response to cellular stress and while the p53 pathway is considered a key determinant of anti-tumor responses in many tumors, its role in cell survival in MB is much less well defined. (aging-us.com)
  • Here, we have examined how HSP90 inhibitors affect LATS1 and the related protein LATS2, two kinases that relay anti-proliferative signals in the Hippo tumor suppressor pathway. (elsevier.com)
  • Taken together, these results identify LATS1 and LATS2 as novel HSP90 clients and show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells. (elsevier.com)
  • Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor. (rush.edu)
  • Thus cells divide uncontrollably, and form tumors. (lifeboat.com)
  • In particular, many targeted drugs used to treat cancer today block proteins produced by cancer-causing genes, or oncogenes , that encourage cancer cells to grow. (cancer.gov)
  • In addition, a recent report showed that ectopic expression of Wwox in breast cancer cells inhibits tumor growth in vivo ( 9 ). (pnas.org)
  • NEDD4-like proteins play important roles regulating gene transcription, embryonic stem cells, cellular transport and activation of T cells. (innovations-report.com)
  • The frequent deletion or mutation of CDKN2 in tumour cells suggests that p16 acts as a tumour suppressor. (nih.gov)
  • We show that wild-type p16 arrests normal diploid cells in late G1, whereas a tumour-associated mutant of p16 does not. (nih.gov)
  • They noted that restored expression of the protein "markedly" decreased leukemic cell propagation without enhancing differentiation of myeloid cells. (cancernetwork.com)
  • Now, results of a new study by Johns Hopkins Kimmel Cancer Center scientists suggests a powerful role for the protein in normal breast cells, acting as a tumor suppressor that halts abnormal cell growth. (innovations-report.com)
  • and their colleagues show that cells without HOXA5 have an increased capacity to renew themselves and are more invasive than normal breast cells -- in short, they become more tumor like. (innovations-report.com)
  • A human breast cell lacking HOXA5 (right) shows protruding structures similar to tumor cells, compared with a normal human breast cell (left). (innovations-report.com)
  • They found that the protein seems to help maintain several traits in normal breast cells, including the ability to adhere to other epithelial cells, and the presence of molecules marking the cells as differentiated and not capable of self-renewal like breast stem cells. (innovations-report.com)
  • When Sukumar and the others depleted the HOXA5 protein in other breast cell lines in the lab, the cells became more immature, or "stem like," as well as more mobile. (innovations-report.com)
  • As a result, breast cells without HOXA5 were more likely to grow aggressively in lab experiments, forming protruding structures similar to those seen as tumor cells begin to metastasize, the scientists found. (innovations-report.com)
  • Chk2 can kill cells by stabilizing p53 tumor suppressor protein or via p53-independent mechanisms, and we established that Chk2-mediated anoikis of intestinal epithelial cells is p53-independent. (sigmaaldrich.com)
  • Memphis, Tennessee - St. Jude Children's Research Hospital scientists have identified a key immune system regulator, a protein that serves as a gatekeeper in the white blood cells that produce the "troops" to battle specific infections. (healthcanal.com)
  • Loss of the Tsc1 protein was associated with a reduction in the number of certain immune cells and a weaker immune response. (healthcanal.com)
  • Alteration of this gene, along with dramatic downregulation of WWOX protein, is shown in the majority of invasive cancer cells. (humpath.com)
  • The UPS functions in the selective degradation of numerous short-lived proteins in eukaryotic cells ( 6 ). (aacrjournals.org)
  • this protein therefore resembles the DlgA protein in being located in a specialized cell junction that functions in information transfer between cells. (biologists.org)
  • In an EST data base search for cDNAs homologous to MM-1, we found a frequent substitution of amino acid 157 of MM-1, from alanine to arginine (A157R), and the substitution was observed more in tumor cells than in normal cells. (sigmaaldrich.com)
  • Interleukin-10 is a pleiotropic homodimeric cytokine produced by immune system cells as well as tumor cells, including melanoma ( 1 , 2 ). (jimmunol.org)
  • We compared gene expression profiles of liver cells with vs without tumor suppressor gene disrupted by sgRNA/Cas9. (mit.edu)
  • Knockdown of HMGA2 delayed formation of xenograft tumors from cells that expressed oncogenic RAS. (mit.edu)
  • Abgent has over fifteen years of experience producing recombinant proteins in E. coli and mammalian cells (CHO and HEK293, etc), and we have added a powerful yeast expression platform to our menu of services. (abgent.com)
  • Furthermore, reintroduction of a wild-type but not mutant VHL cDNA into VHL (−/−) renal carcinoma cells suppresses their ability to form tumors in nude mouse xenograft assays ( 11 , 18 ). (asm.org)
  • The nephrin protein has been detected in glomerular podocytes, in different regions of the brain, and in β-cells of the pancreas. (asnjournals.org)
  • A new study published recently in online Oncogene concluded that HOXA5 protein in normal breast cells acts as a tumor suppressor that halts abnormal cell growth. (holistichealthshow.com)
  • In the study, researchers analyzed gene expression from human breast cell lines lacking HOXA5 and found that the protein seems to help maintain several traits in normal breast cancer, including the ability to adhere to other epithelial cells, and the presence of molecules marking the cells as differentiated and not capable of self-renewal like breast stem cells. (holistichealthshow.com)
  • Stabilization and Reactivation of the p53 Tumor Suppressor Protein in Nontumorigenic Revertants of HeLa Cervical Cancer Cells -- Athanassiou et al. (aacrjournals.org)
  • All of the experimental data gathered so far have been based on studies with maspin localized cytoplasmically, while maspin in breast cancer tumor cells may be located in the cytoplasm, nucleus or both. (biomedcentral.com)
  • We found a strong correlation between nuclear maspin and loss of Ki-67 protein in breast cancer cell lines, while there was no effect in normal epithelial cells from breast. (biomedcentral.com)
  • The characterization of cancer stem cells (CSCs), the identification of oncogene and tumor suppressor genes for CSCs, and the epigenetic study of CSCs and their microenvironments are important topics. (springer.com)
  • Set7/9 methylates the C-terminal region of pRb, both in vitro and in cells, and methylated pRb interacts with heterochromatin protein HP1. (ox.ac.uk)
  • Similarly to hTERT and JunD which are highly expressed in ATL cells, Menin mRNA are clearly detectable in primary ATL cells underlying the importance for HBZ to be able to counteract the repression exerted by this tumor suppressor. (biomedcentral.com)
  • The mechanisms involve the proteins and DNA sequences inside cells. (wikipedia.org)
  • Carcinogen-induced squamous papillomas and oncogenic progression in the absence of the SSeCKS/AKAP12 metastasis suppressor correlate with FAK upregulation. (semanticscholar.org)
  • Consistent with the reduced YAP phosphorylation, there were increased levels of CTGF, a secreted protein that is implicated in tumor proliferation, metastasis, and angiogenesis. (elsevier.com)
  • Taken together, these studies suggest that the suppression domain of WT1 interacts with a cosuppressor protein to mediate inhibition of the WT1 transcriptional activation domain. (nih.gov)
  • Moreover, pVHL interacts with the Par3-Par6-atypical PKC (aPKC) polarity complex, suggesting that pVHL may connect Par3-Par6-aPKC polarity proteins to microtubule capture and ciliogenesis. (rupress.org)
  • Leicester Research Archive: Tumor suppressor protein Pdcd4 interacts with Daxx and modulates the stability of Daxx and the Hipk2-dependent phosphorylation of p53 at serine 46. (le.ac.uk)
  • Herein, we show that p53 physically interacts with specific subregions of steroid receptor coactivator-1 (SRC-1) and its family members, p/ClP (p300/CBP interacting protein), xSRC-3, and AIB1 (amplified in breast cancer), originally isolated as transcription coactivators of nuclear receptors, as demonstrated by the yeast and mammalian two-hybrid tests as well as glutathione S-transferase pull-down assays. (elsevier.com)
  • We have previously described a small region at the N-terminus of WT1 (suppression domain) that inhibits the transcriptional activation domain by contacting a co-suppressor protein. (biochemsoctrans.org)
  • Programmed cell death-4 (PDCD4) is a recently discovered tumor suppressor protein that inhibits protein synthesis by suppression of translation initiation. (aacrjournals.org)
  • Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth. (sdsc.edu)
  • Altogether, these findings suggest that WWOX is a candidate tumor suppressor gene. (pnas.org)
  • We knew ZMYND11 was a candidate tumor-suppressor because it's down-regulated in a number of human cancers, including breast cancer," Shi said. (eurekalert.org)
  • Ng SR, Rideout WM, Akama-Garren EH, Bhutkar A, Mercer KL, Schenkel JM, Bronson RT, Jacks T. CRISPR-mediated modeling and functional validation of candidate tumor suppressor genes in small cell lung cancer. (harvard.edu)
  • We identified an RNA-binding protein, La-related protein 4b (LARP4B), as a candidate tumor suppressor gene in glioma. (aacrjournals.org)
  • Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. (jci.org)
  • WT1 can manifest both tumour suppressor and oncogenic activities, but the reasons for this are not yet clear. (biochemsoctrans.org)
  • We therefore conclude that Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity. (ugent.be)
  • Heat shock protein 90 (HSP90), which regulates the functions of multiple oncogenic signaling pathways, has emerged as a novel anticancer therapeutic target, and multiple small-molecule HSP90 inhibitors are now in clinical trials. (elsevier.com)
  • Although the effects of HSP90 inhibitors on oncogenic signaling pathways have been extensively studied, the effects of these agents on tumor suppressor signaling pathways are currently unknown. (elsevier.com)
  • Nuclear overexpression of p53 protein in transitional cell bladder carcinoma: A marker for disease progression. (labcorp.com)
  • Overexpression of the proteins was achieved by transient transfection with FuGENE 6 transfection reagent according to the manufacturer's instructions (Roche Applied Science). (pnas.org)
  • Overexpression of ZMYND11 in an osteosarcoma cell line and a triple-negative breast cancer cell line inhibited tumor growth. (eurekalert.org)
  • Diverse stress stimuli, such as high osmolarity and overexpression of the human β-amyloid precursor protein, can promote PAR-1 activation and tau phosphorylation in an LKB1-dependent manner. (jneurosci.org)
  • We find that ectopic overexpression of p14ARF suppresses endogenous and ectopic cap-dependent protein translation, consistent with other studies. (jcancer.org)
  • The researchers found that high expression of the tumor-suppressor ZMYND11 is associated with longer survival for patients with triple-negative breast cancer. (eurekalert.org)
  • A protein known as WWP2 appears to play a key role in tumor survival, a research team headed by a scientist at The University of Texas MD Anderson Cancer Center reports in an advance online publication of Nature Cell Biology. (innovations-report.com)
  • Similarly, patients with tumors containing low amounts of HOXA5 protein also had lower cancer relapse-free survival rates. (innovations-report.com)
  • Those cases with intermediate or high p16/INK4A tumour expression had a significantly better post-diagnosis survival than those cases whose tumours lost p16 expression," writes Cormac J. Jennings of Beaumont Hospital in Dublin, Ireland. (survivingmesothelioma.com)
  • We associated decreased levels of NF1 and increased levels of its downstream protein HMGA2 with survival times of patients with HCC. (mit.edu)
  • New experiments showed that altered forms of the Fhit protein that bind but don't cleave ApppA are actually still working in tumor suppression. (bio-medicine.org)
  • Thus, inhibition of elongin (SIII) activity may contribute to tumor suppression by pVHL. (asm.org)
  • The p73 protein is a structural and functional homolog of the p53 tumor suppressor protein ( 12 , 13 ). (pnas.org)
  • The adenomatous polyposis coli (APC) 1 gene is a tumor suppressor gene linked to familial adenomatous polyposis (FAP) and to the initiation of sporadic human colorectal cancer ( 9 , 18 , 20 , 32 , 40 ). (rupress.org)
  • Birt-Hogg-Dube (BHD) is a tumor suppressor gene syndrome associated with fibrofolliculomas, cystic lung disease, and chromophobe renal cell carcinoma. (harvard.edu)
  • Recently, it was shown that nephrin is redistributed in the glomerular podocytes of patients with minimal-change nephropathy, membranoproliferative glomerulonephritis, and other renal disorders, suggesting a more general role for this protein in glomerular disease ( 3 ). (asnjournals.org)
  • Physical interaction of p73 with different proteins may modulate its transcriptional as well as its biological activity ( 16 , 17 ). (pnas.org)
  • We find that a region within the domain of WT1 attributed to transcriptional repression is a potent suppressor of the activation domain at several promoters and in different cell types. (nih.gov)
  • The results suggest that MM-1 is a novel candidate for a tumor suppressor that controls the transcriptional activity of c-Myc. (sigmaaldrich.com)
  • These two proteins, when bound to elongin A, generate a transcriptional elongation complex called elongin or SIII ( 1 ). (asm.org)
  • Isoforms that lack the KTS sequence (Wt1−KTS) are potent transcriptional activators and bind preferentially to DNA, whereas Wt1+KTS proteins may also have a role in RNA binding. (asnjournals.org)
  • Importantly, LATS1 signaling was disrupted by 17-AAG in tumor cell lines in vitro and clinical ovarian cancers in vivo as shown by reduced levels of LATS1 and decreased phosphorylation of the LATS substrate YAP, an oncoprotein transcriptional coactivator that regulates genes involved in cell and tissue growth, including the CTGF gene. (elsevier.com)
  • This architecture of p53 in toto suggests novel mechanisms for structural plasticity, which enables the protein to bind variably spaced DNA target sequences, essential for p53 transactivation and tumour suppressor functions. (whiterose.ac.uk)
  • Peptides spanning the CXXC region of thiol-protein oxidoreductases retain some biochemical properties of the full-length protein. (tudelft.nl)
  • Check out links to articles that cite our custom service antibodies, peptides, and proteins in major peer-reviewed journals, organized by research category. (abgent.com)
  • Here we show that phosphorylation of PAR-1 by the tumor suppressor protein LKB1 is required for PAR-1 activation, which in turn promotes tau phosphorylation in Drosophila . (jneurosci.org)
  • The study of these and other tumor suppressor genes in Drosophila is providing new evidence supporting the critical role of cell interactions and specialized apical junctions in controlling epithelial cell proliferation. (biologists.org)
  • The COOH-terminal third of the APC protein contains a basic region and has recently been shown to bind the human homologue of the Drosophila disc large (Dlg) tumor suppressor protein ( 23 ) and a novel protein EB1 ( 52 ). (rupress.org)
  • In this study, we demonstrate that these E6 proteins can bind to the second PDZ domain of the human homologue of the Drosophila discs large tumor suppressor protein (hDLG) through their C-terminal XS/TXV/L (where X represents any amino acid, S/T serine or threonine, and V/L valine or leucine) motif. (elsevier.com)
  • Analysis of Protein Array containing more than 19,000 full-length human proteins using p53 Mouse Monoclonal Antibody (rTP53/1739). (neobiotechnologies.com)
  • The activity of Rb (retinoblastoma protein) is regulated by phosphorylation and acetylation events. (portlandpress.com)
  • These results reveal a new function for the tumor suppressor protein LKB1 in a signaling cascade through which the phosphorylation and function of tau is regulated by diverse signals under physiological and pathological conditions. (jneurosci.org)
  • Phosphorylation of the translation inhibitor 4EBP1 by mTOR releases it from the translation initiation factor eIF4E to initiate cap-dependent protein translation. (ahajournals.org)
  • The tumor suppressor protein p53 appears to be regulated by various means including phosphorylation. (spandidos-publications.com)
  • The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. (biomol.com)
  • Promyelocytic leukemia (PML) protein is a tumor suppressor implicated in tumorigenesis in different tissues. (frontiersin.org)
  • also known as Rfwd2) in tumorigenesis, providing evidence for both the oncoprotein c-Jun and the tumor suppressor p53 as its targets. (ugent.be)
  • In conclusion, our results demonstrate that SIRT1 is an in vitro and in vivo deacetylase for the Rb tumour suppressor protein. (portlandpress.com)
  • Ectopic WWOX exhibits proapoptotic and tumor inhibitory functions in vitro and in vivo, probably interacting with growth regulatory proteins p53, p73 and others. (humpath.com)
  • Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis. (labcorp.com)
  • Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. (labcorp.com)
  • Low, undetectable expression or aberrant transcripts of WWOX were reported in several tumor cell lines of different origins ( 2 , 8 ). (pnas.org)
  • HOUSTON -- A tumor-suppressing protein acts as a dimmer switch to dial down gene expression. (eurekalert.org)
  • The theory holds that histone proteins, which combine with DNA to form chromosomes, are more intimately involved in gene expression than their general role of facilitating or hindering gene activation suggests. (eurekalert.org)
  • Prion protein expression aids cellular uptake and veratridine-induced release of copper. (biomedsearch.com)
  • A team of doctors in Ireland and Italy measured the expression of the tumor suppressor protein p16/INK4A in tumor biopsy specimens from 88 pleural mesothelioma patients. (survivingmesothelioma.com)
  • Mesothelioma patients with the highest p16 levels who had chemotherapy lived longer than patients whose tumors had lost p16 expression, even if they also had chemotherapy. (survivingmesothelioma.com)
  • To further characterize MDA-7/IL-24 expression patterns in the human immune system, MDA-7/IL-24 protein levels were examined in human PBMC. (jimmunol.org)
  • Most FAP patients carry one allelic APC mutation in the 5′ half of the coding sequence, which usually causes chain termination and results in the expression of truncated proteins. (rupress.org)
  • For those of you wanting to study tumor suppressor expression levels by Western blot analysis we offer PrecisionAb™ Western blot validated antibodies. (bio-rad-antibodies.com)
  • This is the first report indicating YAP as a tumor suppressor, revealing its decreased expression in breast cancer as well as demonstrating the functional implications of YAP loss in several aspects of cancer signaling. (icr.ac.uk)
  • Background & Aims It has been a challenge to identify liver tumor suppressors or oncogenes due to the genetic heterogeneity of these tumors. (mit.edu)
  • Accumulation of p53 tumor suppressor gene protein: An independent marker of prognosis in breast cancers. (labcorp.com)
  • Previous work has shown that Mtss1 has a tumor suppressive function in various cancers. (cancernetwork.com)
  • Many breast cancers are marked by a lack of HOXA5 protein, a gene product known to control cell differentiation and death, and lower levels of the protein correspond to poorer outcomes for patients. (innovations-report.com)
  • Learning more about the biological impact of the HOXA5 protein, which is absent so frequently in breast cancers, may eventually help scientists develop new therapies to treat this disease," says Sukumar. (innovations-report.com)
  • BRCA1-associated protein-1 (BAP1), a deubiquitinating enzyme of unknown cellular function, is mutated in breast and lung cancers. (aacrjournals.org)
  • BRCA1-associated protein-1 (BAP1) is a component of the ubiquitin proteasome system (UPS) that has been implicated in lung and breast cancers ( 3 ). (aacrjournals.org)
  • Structure determined for p53 tumor suppressor protein as bound to DNA for anti-cancer activity ( More than half of human cancers involve. (bio-medicine.org)
  • Clearly, a detailed view of the p53 protein in direct contact with DNA could provide important insights into preventing and treating an array of human cancers. (bio-medicine.org)
  • Given the fact that p53 is an important tumor suppressor that is mutated in the majority of human cancers, this will undoubtedly be useful information. (bio-medicine.org)
  • One new insight from the current study, for example, is that the point of contact between the two core domains of a pair of p53 proteins forming a dimer tracks to a part of the protein often mutated in cancers. (bio-medicine.org)
  • In the majority of cervical cancers, DNAs of high-risk mucosotpropic human papillomaviruses (HPVs), such as type 16, are maintained so as to express two vital proteins, E6 and E7, suggesting an essential importance to carcinogenesis. (elsevier.com)
  • These results suggest an intriguing possibility that interaction between the E6 protein and hDLG or other PDZ domain-containing proteins could be an underlying mechanism in the development of HPV-associated cancers. (elsevier.com)
  • Tumor development in this setting is due to somatic loss or mutation of the remaining wild-type VHL allele ( 9 , 17 ). (asm.org)
  • DNase footprinting and mutation analysis identify a Wt1 responsive element in the nephrin promoter, which is required for the binding of Wt1 protein. (asnjournals.org)
  • tumor formation was monitored and tumors were analyzed by histology and immunohistochemistry. (mit.edu)
  • Tissue sections from 166 patients with invasive ductal breast cancer were stained by immunohistochemistry for maspin and Ki-67 protein. (biomedcentral.com)
  • Bio-Rad offers a variety of antibodies for analyzing tumor suppressor proteins by ELISA, Flow Cytometry, Immunofluorescence, Immunohistochemistry, Immunoprecipitation and Western Blotting. (bio-rad-antibodies.com)
  • Examination of tumors by immunohistochemistry demonstrated significant loss of YAP protein. (icr.ac.uk)
  • The cardinal feature of this hereditary cancer syndrome is the development of multiple vascular tumors called hemangioblastomas in the central nervous system and retina combined with clear cell carcinoma of the kidney and pheochromocytoma. (rupress.org)
  • Dr. Brenner and his co-workers sought to understand how the Fhit protein suppresses tumor formation. (bio-medicine.org)
  • The loss of the phosphate alters PIP3's activity and causes a chain reaction of effects on other important regulatory proteins that ultimately suppresses cell division and migration, both deadly aspects of tumor progression. (technologynetworks.com)
  • We also found that this variant, H3.3, is modified by methylation to create a specific epigenetic landscape that is accommodated by the tumor-suppressing protein ZMYND11. (eurekalert.org)
  • Methylation, the attachment of a methyl group to a gene or protein, and other types of histone modifications are considered epigenetic factors, which modify a gene's behavior without changing its DNA coding. (eurekalert.org)
  • At the epigenetic level, DNA promoter methylation of specific genes, often tumor suppressors, has been associated with disease progression. (cancernetwork.com)
  • Lysine methylation regulates the pRb tumour suppressor protein. (ox.ac.uk)
  • Our results indicate that methylation can influence the properties of pRb, and raise the interesting possibility that methylation modulates pRb tumour suppressor activity. (ox.ac.uk)
  • VHL disease is an autosomal-dominant disorder, and tumor development in VHL disease is linked to somatic inactivation of the remaining wild-type VHL allele, leading to loss of the wild-type VHL gene product, VHL protein (pVHL). (rupress.org)
  • BAP1 is a DUB originally identified as a protein interacting with the RING finger domain of the breast cancer susceptibility gene product BRCA1 ( 3 ). (aacrjournals.org)
  • This builds upon previous research finding that many breast cancer patients have a lower level of HOXA5 protein, a gene product known to control cell differentiation and death, and lower levels of the protein corresponded to poorer outcomes for patients. (holistichealthshow.com)
  • Recognizes a 53kDa protein, which is identified as p53 suppressor gene product. (neobiotechnologies.com)
  • Cullins are a recently identified family of proteins that exhibit significant sequence similarity to the yeast Cdc53 protein and hence are suspected of functioning to target certain proteins for ubiquitin-dependent proteolysis ( 15 , 19 , 23 ). (asm.org)
  • D-type cyclins, in association with the cyclin-dependent kinases Cdk4 or Cdk6, promote progression through the G1 phase of the cell cycle by phosphorylating the retinoblastoma protein (RB). (nih.gov)
  • The pRb tumour suppressor protein has a central role in coordinating early cell cycle progression. (ox.ac.uk)
  • Using green fluorescent protein-tagged end-binding protein 1 to label microtubule plus ends, we found that pVHL does not affect the microtubule growth rate but is needed to orient the growth of microtubules toward the cell periphery, a prerequisite for the formation of cilia. (rupress.org)
  • Z- and S- Score: The Z-score represents the strength of a signal that a monoclonal antibody (MAb) (in combination with a fluorescently-tagged anti-IgG secondary antibody) produces when binding to a particular protein on the HuProtTM array. (neobiotechnologies.com)
  • The specificity of this monoclonal antibody to its intended target was validated by HuProtTM Array, containing more than 19,000, full-length human proteins. (neobiotechnologies.com)
  • The tumor suppressor protein p16INK4a (inhibitor of CDK4) is one of the most direct links between cell-cycle control and cancer. (nih.gov)
  • The p16INK4a gene is frequently inactivated in human tumors, and inheritance of mutant alleles results in susceptibility to several types of cancer. (nih.gov)
  • If a person inherits only one functional copy of the p53 gene from their parents, they are predisposed to cancer and usually develop several independent tumors in a variety of tissues in early adulthood. (lifeboat.com)
  • But another class of proteins important to cancer development has proven more difficult to manipulate: tumor-suppressor proteins. (cancer.gov)
  • The team zeroed in on one such protein, WWP1, which was already known to be produced in abundance in some types of cancer. (cancer.gov)
  • It does this by reading a chemical message attached to another protein that's tightly intertwined with DNA, a team led by scientists at The University of Texas MD Anderson Cancer Center reported at the AACR Annual Meeting 2014. (eurekalert.org)
  • An analysis of ZMYND11 levels in the tumors of 120 triple-negative breast cancer patients showed that those with high levels of the protein had an 80 percent probability of surviving for 10 years while those with low levels had a 50 percent probability. (eurekalert.org)
  • Sukumar and her colleagues also analyzed data from two international breast cancer genetic data sets and found that the lower the amount of HOXA5 in a tumor, the higher the grade of breast cancer in the patient. (innovations-report.com)
  • The scientists are planning further study of HOXA5's role in breast cancer, following up on this work and a study published by Sukumar's lab in 2000 that showed a connection between low levels of HOXA5 and the well-known tumor suppressor protein p53. (innovations-report.com)
  • St. Jude is the national coordinating center for the Pediatric Brain Tumor Consortium and the Childhood Cancer Survivor Study. (healthcanal.com)
  • We show that BAP1 fulfills another criterion of a genuine tumor suppressor because cancer-associated BAP1 mutants are deficient in deubiquitinating activity. (aacrjournals.org)
  • The identification of the deubiquitinating enzyme BAP1 as a tumor suppressor may lead to further understanding of how the ubiquitin proteasome system contributes to cancer and aid in the identification of new targets for cancer therapy. (aacrjournals.org)
  • MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer. (sigmaaldrich.com)
  • Apoptotic proteins up-regulated or activated by Ad-MDA7 include p53, caspases, Bax, and Bak ( 15 ), and attempts for its use in human cancer gene therapy are underway. (jimmunol.org)
  • To validate the top 10 candidate tumor suppressors from this screen, we collected data from patients with hepatocellular carcinoma (HCC) using the Cancer Genome Atlas and COSMIC databases. (mit.edu)
  • Results We identified 4 candidate liver tumor suppressor genes not previously associated with liver cancer (Nf1, Plxnb1, Flrt2, and B9d1). (mit.edu)
  • Here we have compared the effects of the p14ARF (Alternate Reading Frame) tumor suppressor, a translational suppressor frequently overexpressed in cancer, on cap-dependent translation versus cap-independent translation from the EMCV viral IRES often used in bicistronic gene transfer vectors. (jcancer.org)
  • Protein-A Breast Cancer Tumor Suppressor. (holistichealthshow.com)
  • Cancer - Copy - Tumor-suppressor genes help prevent. (coursehero.com)
  • The tumor suppressor protein Pdcd4 is a nuclear/cytoplasmic shuttling protein that has been implicated in the development of several types of human cancer. (le.ac.uk)
  • Maspin, which is classified as a tumor suppressor protein, is downregulated in many types of cancer. (biomedcentral.com)
  • 53BP1 contains two breast cancer susceptibility gene 1 COOH terminus (BRCT) motifs, which are present in several proteins involved in DNA repair and/or DNA damage-signaling pathways. (rupress.org)
  • The focus of this study was to determine if early detection of mutant p53 accumulation may be an early indicator of tumor aggressiveness and transformation to invasive breast cancer. (ac.ir)
  • On the basis of this function and its location at 11q22.2, a site of frequent loss of heterozygosity (LOH) in breast cancer, we investigated whether YAP is a tumor suppressor in breast. (icr.ac.uk)
  • Medulloblastoma (MB), a primitive neuroectodermal tumor, is the most common malignant childhood brain tumor and remains incurable in about a third of patients. (aging-us.com)
  • Complexes were captured with glutathione-Sepharose, and bound protein was detected by HA immunoblot. (nih.gov)
  • MIF-(50-65) and its variant bound to the MIF-binding protein JAB1 and enhanced cellular levels of p27Kip1. (tudelft.nl)
  • Shown here are the DNA-binding regions of the p53 tumor suppressor protein, bound to DNA. (sciencephoto.com)
  • To date, however, despite having learned a good deal about the protein's biochemistry over the years, scientists have been unable to "see" the protein ?using the tools of structural biology ?bound to DNA in its naturally occurring form. (bio-medicine.org)
  • Now, in a new study featured as a "paper of the week" and on the cover of the July 21 issue of the Journal of Biological Chemistry, researchers at The Wistar Institute have successfully determined the three-dimensional structure of the p53 protein bound as a dimer to DNA and used the structure to produce an accurate model of the p53 tetramer bound to DNA. (bio-medicine.org)
  • When an IRES segment is located between two genes in a eukaryotic mRNA molecule, it can drive translation of the downstream protein coding region independently of the 5'-cap structure bound to the message. (jcancer.org)
  • Chen noted that more research is needed to determine whether WWP2 is functionally important in tumors or in tumor formation. (innovations-report.com)
  • Neurofibromatosis 2 tumor suppressor protein, merlin, forms two functionally important intramolecular associations. (biomedsearch.com)
  • The melanoma differentiation-associated gene 7 ( mda-7 ) has been studied primarily in the context of its tumor suppressor activity. (jimmunol.org)
  • Loss of the retinoblastoma protein (pRb) induces a cell-nonautonomous defect in both erythroid and neuronal differentiation. (eur.nl)
  • As their name suggests, these proteins normally act to stop abnormal cell growth. (cancer.gov)
  • This work suggests that the threshold for loss of tumor suppressor activity, in terms of the disruption of p53's tetrameric structure, could be extremely low. (springer.com)
  • This suggests that the interface between the two proteins of the dimer is likely as important for the proper functioning of the tetramer as its interface with DNA, which also depends on the interface of the core domains of the two p53 proteins that form a dimer. (bio-medicine.org)
  • Protein p53 is an important checkpoint in the cell cycle, ensuring the integrity of DNA replication. (sciencephoto.com)
  • The tumor suppressor protein p53 exerts its cell cycle-regulatory effects through its ability to function as a sequence-specific DNA-binding transcription factor. (elsevier.com)