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 RASSF4 gene (Protein Coding), Ras Association Domain Family Member 4, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
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
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 1 (RASSF1), transcript variant F, mRNA. (H00011186-R06) - Products - Abnova
Homo sapiens Ras association (RalGDS/AF-6) domain family 5 (RASSF5), transcript variant 1, mRNA. (H00083593-R01) - Products - Abnova
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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 producing 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 ...
Proteins, Transcription factors, Tumor suppressor genes, Apoptosis, Genes mutated in mice, Aging-related proteins). ... p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) ... "The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and ... Wikimedia Commons has media related to Tumor suppressor protein p53. "p53 Knowledgebase". Lane Group at the Institute of ...
P53 The p53 tumor suppressor protein. National Center for Biotechnology Information (US). 1998. Wikiquote has quotations ... The p53 gene is known as the tumor suppressor gene. 1999 Medal of Honor for Clinical Research, American Cancer Society 1998 ... which is caused by germline mutations of the p53 tumor suppressor gene and genetically predisposes families to high rates of ... 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 suppressor gene". "Basal cell carcinoma tumor suppressor protein". "Erivedge® (Vismodegib) , ... 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), their 1996 live ...
Several function as tumor suppressor proteins. Cell cycle progression is delayed or stopped by cyclin-dependent kinase ... A cyclin-dependent kinase inhibitor protein is a protein which inhibits the enzyme cyclin-dependent kinase (CDK). ... 43-kDa mitogen-activated protein kinase signaling pathway in human tumors". Oncogene. 18 (3): 813-22. doi:10.1038/sj.onc. ... Seven cyclin-dependent kinase inhibitor proteins have thus far been identified. They are named by the small letter "p" followed ...
... is a protein which has been implicated as a putative tumor suppressor. It is structurally similar to the protein latexin, which ... So et al.: "Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia." Cancer ... Although the restoration of TIG1 did not prevent tumor growth in these mice, the average size of the tumors showed a 2.4-fold ... and its mechanism of tumor suppression is largely unknown. The amino acid sequence of the protein TIG1 is as follows: N ...
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. ...
... proteins are tumor suppressors and loss-of-function mutations lead to carcinogenesis. INK4 proteins are highly similar in ... mutations in-vivo often responded by activating the INK4A/ARF/INK4B locus that encodes the INK4 tumor suppressor proteins. The ... Li J, Poi MJ, Tsai MD (June 2011). "Regulatory mechanisms of tumor suppressor P16(INK4A) and their relevance to cancer". ... Rayess H, Wang MB, Srivatsan ES (April 2012). "Cellular senescence and tumor suppressor gene p16". International Journal of ...
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/ ...
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: ...
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?". Molecular Cancer. 10 (1): 101. doi:10.1186/1476 ... 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 ...
... 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 ... Human proteins, Tumor suppressor genes, Armadillo-repeat-containing proteins). ... 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 (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/ ...
... protein name abbreviated pRb; gene name abbreviated Rb, RB or RB1) is a proto-oncogenic tumor suppressor protein that is ... September 2003). "Tumor suppressor pRB functions as a co-repressor of the CCAAT displacement protein (CDP/cut) to regulate cell ... Momand J, Wu HH, Dasgupta G (January 2000). "MDM2--master regulator of the p53 tumor suppressor protein". Gene. 242 (1-2): 15- ... Hirsch HA, Gu L, Henry RW (December 2000). "The retinoblastoma tumor suppressor protein targets distinct general transcription ...
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 ... 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 proteins encoded by most tumor suppressor genes inhibit cell proliferation or survival. Inactivation of tumor suppressor ... Retinoblastoma protein (pRb). pRb was the first tumor-suppressor protein discovered in human retinoblastoma; however, recent ... TCF21 gene discovery at Ohio State University Drosophila Oncogenes and Tumor Suppressors - The Interactive Fly Tumor Suppressor ... In most cases, tumor suppressor proteins inhibit the same cell regulatory pathways that are stimulated by the products of ...
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. Two ... "Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein". J. ...
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. ...
Based on its role in several tumor types, the LZTR1 protein is thought to act as a tumor suppressor. Tumor suppressors are ... Genes on human chromosome 22, Kelch proteins, Tumor suppressor genes). ... Intracellularly, LZTR proteins will be found in the Golgi apparatus. Studies suggest that the LZTR1 protein may help stabilize ... Nacak TG, Leptien K, Fellner D, Augustin HG, Kroll J (Feb 2006). "The BTB-kelch protein LZTR-1 is a novel Golgi protein that is ...
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. ...
... is an apoptosis inducing protein that is able to regulate the function of tumor suppressor. More specifically, P14ARF is ... "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2021-08-01. (CS1 maint: url- ... p14ARF is a protein that is a known tumor suppressor.It does this by controlling cell proliferation and cell survival, however ... a protein in which in humans is modulated by the PANO1 gene. P14ARF is known to function as a tumor suppressor. When PANO1 is ...
CEBPD transcription factor as tumor suppressor as well as tumor promoter in breast epithelial cells and cells of the tumor ... Sterneck began to study the functions of CCAAT-enhancer-binding proteins (C/EBP) transcription factors, including their roles ... investigates signaling pathways with emphasis on pro-inflammatory molecules in breast epithelial cells and cells of the tumor ...
... a candidate neuroblastoma tumour suppressor gene". Human Genetics. 106 (4): 406-13. doi:10.1007/s004390000257. PMID 10830907. ... 2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. ... The protein caspase DNase is an endonuclease involved in the cell apoptotic process that facilitates the DNA breakup. Cell ... It also depends on the activity of a protein or a common signal. The factor that seems to induce more cell differentiation is ...
Shao L, Cui Y, Li H, Liu Y, Zhao H, Wang Y, Zhang Y, Ng KM, Han W, Ma D, Tao Q (October 2007). "CMTM5 exhibits tumor suppressor ... This family consists of 9 proteins although most of them are known to have one or more isoforms. These proteins are: chemokine- ... These findings suggest that the CMTM5 gene may act as a tumor suppressor gene, i.e. a normal gene whose product(s) inhibit the ... Li H, Guo X, Shao L, Plate M, Mo X, Wang Y, Han W (March 2010). "CMTM5-v1, a four-transmembrane protein, presents a secreted ...
... an imprinted putative tumor suppressor gene in ovarian and breast carcinomas". Proceedings of the National Academy of Sciences ... of breast and ovarian cancers the protein encoded by DIRAS3 is not expressed, suggesting that it functions as a tumor ... "DNA sequence polymorphisms within the bovine guanine nucleotide-binding protein Gs subunit alpha (Gsα)-encoding (GNAS) genomic ... "A phylogenetic approach to test for evidence of parental conflict or gene duplications associated with protein-encoding ...
Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in ... To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special ... Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; ... The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, ...
In normal cells, α-catenin may act as a tumor suppressor and can help prevent the adhesion defects associated with cancer. On ... They exhibit a high degree of protein dynamics, alone or in complex. Several types of catenins work with N-cadherins to play an ... 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 ...
... a novel tumor suppressor gene, in esophageal cancer and its inhibitory effect on the tumor growth in vitro and in vivo". Int. J ... Augurin is a protein that in humans is encoded by the C2orf40 gene. GRCh38: Ensembl release 89: ENSG00000119147 - Ensembl, May ... Li W, Liu X, Zhang B, Qi D, Zhang L, Jin Y, Yang H (July 2010). "Overexpression of candidate tumor suppressor ECRG4 inhibits ... Li LW, Li YY, Li XY, Zhang CP, Zhou Y, Lu SH (February 2011). "A novel tumor suppressor gene ECRG4 interacts directly with ...
It is proposed that miR-137 also acts as a tumour suppressor in melanoma cells by down-regulating both MITF and CDK6. In mouse ... It is thus postulated that miR-137 plays a tumour suppressive role by negatively modulating LSD1 protein expression. Liu et al ... miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types ... KDM4A targets CHD5, a tumour suppressor and positive regulator p53 expression. It was observed that miR-137 expression is lost ...
"The parafibromin tumor suppressor protein is part of a human Paf1 complex". Mol. Cell. Biol. 25 (2): 612-20. doi:10.1128/MCB. ... 2004). "Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP)". J ... 1995). "Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31". Am. J. ... is a protein which in humans is encoded by the CDC73 gene. Parafibromin, LEO1, PAF1, and CTR9 form the PAF protein complex, ...
Because these genes are instrumental in prevention of tumor formation, they are known as tumor suppressors. The cip/kip family ... The G2 checkpoint is mainly regulated by the tumor protein p53. If the DNA is damaged, p53 will either repair the DNA or ... Narasimha AM, Kaulich M, Shapiro GS, Choi YJ, Sicinski P, Dowdy SF (June 2014). "Cyclin D activates the Rb tumor suppressor by ... The un-phosphorylated Rb tumour suppressor functions in inducing cell cycle exit and maintaining G0 arrest (senescence). In the ...
... a novel RBCC family member isolated from a hemopoietic lineage switch is a candidate tumour suppressor. J Biol Chem 279:8181- ... Blood 111: 1946-1950 (2008) Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that influences erythropoietin- ... Nature 507:462-470 (2014) Complementing tissue characterisation by integrating transcriptome profiling from the Human Protein ...
As a part of their functions, the TSC1 and TSC2 tumor suppressor genes act to suppress the abnormal growth of cells by ... contributing to the suppression of the mammalian target of rapamycin (i.e. mTOR) protein that promotes cell growth and ... loss-of-function mutations in one of the two normally paired TSC1 or one of the two normally paired TSC2 tumor suppressor genes ... shave excision of the tumor with phenolization (i.e. excision of the tumor's protruding portion followed by treatment of the ...
... a tumor suppressor implicated in multiple forms of cancer, namely breast cancer. Furthermore, studies have established a strong ... Furthermore, SINEs frequently contain motifs for YY1 polycomb proteins. YY1 is a zinc-finger protein that acts as a ... Thereafter, one of the strands is incorporated into a multi-protein RNA-induced silencing complex (RISC). Among these proteins ... encodes a protein which binds to RNA and acts as a chaperone to facilitate and maintain the LINE protein-RNA complex structure ...
... similar to tumor suppressor PTEN. Yet the 5-phosphatase SHIP proteins synthesis of PI(3,4)P2 has been linked to tumor cell ... Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell. ( ... Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell. ( ... Following this release, T308 in the proteins activation loop and S437 in the proteins hydrophobic domain are phosphorylated by ...
2005). "The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1". Oncogene. 24 (12): 2076-86. doi: ... Protein salvador homolog 1 is a protein that in humans is encoded by the SAV1 gene. WW domain-containing proteins are found in ... The encoded protein is 94% identical to the mouse protein at the amino acid level. GRCh38: Ensembl release 89: ENSG00000151748 ... This gene encodes a protein which contains 2 WW domains and a coiled-coil region. It is ubiquitously expressed in adult tissues ...
This gene is also a candidate tumor suppressor gene for human breast cancer. FABP3 is known to interact with TNNI3K in the ... Huynh HT, Larsson C, Narod S, Pollak M (Jun 1995). "Tumor suppressor activity of the gene encoding mammary-derived growth ... Heart-type fatty acid binding protein (hFABP) also known as mammary-derived growth inhibitor is a protein that in humans is ... Heart-type Fatty Acid-Binding Protein (H-FABP) is a small cytoplasmic protein (15 kDa) released from cardiac myocytes following ...
... which results in different gene expression that can activate oncogenes and inactivate tumor-suppressor genes. Ultimately, this ... Portal: Biology (Articles with short description, Short description matches Wikidata, Genes on human chromosome 2, Protein ... Specific mutations in the isocitrate dehydrogenase gene IDH1 have been found in several tumor types. Notably brain tumors ... Patients whose tumor had an IDH1 mutation had longer survival. Furthermore, mutations of IDH2 and IDH1 were found in up to 20% ...
Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in ... The eukaryotic proteasome recognizes degradable proteins, including damaged proteins for protein quality control purpose or key ... and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, ABL). The ... "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". ...
... a candidate suppressor of tumor metastasis". Science. 261 (5120): 478-80. Bibcode:1993Sci...261..478P. doi:10.1126/science. ... "Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development". Nature. 342 (6246): 177-80. Bibcode: ... interacts directly with the metastasis suppressor nm23-H2, and both proteins are targeted to newly formed cell adhesion sites ... "The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1". Nucleic Acids Res. 30 (24): 5465-75 ...
August 2019). "RNF144A functions as a tumor suppressor in breast cancer through ubiquitin ligase activity-dependent regulation ... RNF144A is most closely related to RNF144B at the protein level, and the two proteins together comprise a subdomain within the ... "RNF144A - E3 ubiquitin-protein ligase RNF144A - Homo sapiens (Human) - RNF144A gene & protein". www.uniprot.org. UniProt. ... "RNF144A ring finger protein 144A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. National Center for Biotechnology ...
"The human tumor suppressor arf interacts with spinophilin/neurabin II, a type 1 protein-phosphatase-binding protein". The ... The ARF product functions as a stabilizer of the tumor suppressor protein p53, as it can interact with and sequester MDM2, a ... This gene is frequently mutated or deleted in a wide variety of tumors and is known to be an important tumor suppressor gene. ... multiple tumor suppressor 1 and numerous other synonyms), is a protein that slows cell division by slowing the progression of ...
... 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 ... In 1914 an American neurosurgeon, Harvey Cushing, reported on a patient with a pituitary tumour on whom he had operated. The ... transition in the second codon position of the 74th codon in the protein) mutation in the PRKAR1A gene, confirming a diagnosis ...
The protein, which contains a C2-C2 zinc finger-like domain that can bind to zinc, can enhance the tumor suppressor activity of ... "The S29 ribosomal protein increases tumor suppressor activity of K rev-1 gene on v-K ras-transformed NIH3T3 cells". Biochimica ... 40S ribosomal protein S29 is a protein that in humans is encoded by the RPS29 gene. Ribosomes, the organelles that catalyze ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi: ...
Zhang QQ, Xu H, Huang MB, Ma LM, Huang QJ, Yao Q, Zhou H, Qu LH (March 2012). "MicroRNA-195 plays a tumor-suppressor role in ... MicroRNA 195 is a protein that in humans is encoded by the MIR195 gene. microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs ... Gonsalves C, Kalra VK (November 2010). "Endothelin-1-induced macrophage inflammatory protein-1beta expression in monocytic ... that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to ...
"ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation ... Enhancer of polycomb homolog 2 (Drosophila) is a protein that in humans is encoded by the EPC2 gene. GRCh38: Ensembl release 89 ... May 2008). "A genome-wide association study identifies protein quantitative trait loci (pQTLs)". PLOS Genetics. 4 (5): e1000072 ...
... tumour hypoxia and DNA damage. The gene changes consistently observed in MRI-visible tumours include loss of tumour suppressor ... Transport protein ZIP1 is responsible for the transport of zinc into prostate cells. One of zinc's important roles is to change ... Other tumor suppressor genes that are thought to play a role include PTEN and KAI1. "Up to 70 percent of men with prostate ... It is called a tumor suppressor gene product for the gene SLC39A1. The cause of the epigenetic silencing is unknown. Strategies ...
... a tumor suppressor protein that preferentially binds to cruciform structures, is responsible for over 50% of human tumor ... The BRCA1 protein, a tumor suppressor that functions in DNA repair, binds preferentially to cruciform structures. Mutations in ... Stros M, Muselíková-Polanská E, Pospísilová S, Strauss F (June 2004). "High-affinity binding of tumor-suppressor protein p53 ... Another example of cruciform structure significance is seen in the interaction between p53, a tumor suppressor, and cruciform ...
Expression of this gene is activated by the phosphatase and tensin homolog, a tumor suppressor. Alternate splicing results in ... This gene encodes a protein with an ankyrin repeat region and two BTB/POZ domains, which are thought to be involved in protein- ... Ankyrin repeat and BTB/POZ domain-containing protein 1 is a protein that in humans is encoded by the ABTB1 gene. ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode: ...
Von Hippel-lindau Disease Tumor Suppressor (human). Find diseases associated with this biological target and compounds tested ...
Tumor suppressor proteins, p53 protein, Fourier transform spectroscopy, Mass spectroscopy, Fragmentation reactions, Cysteine ... Identification of two reactive cysteine residues in the tumor suppressor protein p53 using top-down FTICR mass spectrometry ... 2011) Identification of two reactive cysteine residues in the tumor suppressor protein p53 using top-down FTICR mass ... The tumor suppressor p53 is a redox-regulated transcription factor involved in cell cycle arrest, apoptosis and senescence in ...
RNA binding by the Wilms tumor suppressor zinc finger proteins. A A Caricasole, Antonio Duarte, S H Larsson, N D Hastie, M ... Dive into the research topics of RNA binding by the Wilms tumor suppressor zinc finger proteins. Together they form a unique ...
Docking-dependent ubiquitination of the interferon regulatory factor-1 tumor suppressor protein by the ubiquitin ligase CHIP.. ... Docking-dependent ubiquitination of the interferon regulatory factor-1 tumor suppressor protein by the ubiquitin ligase CHIP. ...
A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 ... Overexpression of DAB2IPs rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR- ... The incidence of pancreatic neuroendocrine tumor (PNET) is increasing, and it presents with various clinical manifestations and ... A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 ...
... is a recombinant Rat protein produced in E. coli using Prokaryotic expression. ... Protein RCA1, Rat RCA1 Protein, Rat RCA1, Rat protein RCA1, VHL1 protein, Protein VHL1, Rat VHL1 Protein, Rat VHL1, Rat protein ... HRCA1, RCA1, VHL1, Von Hippel-Lindau Syndrome, HRCA1 protein, Protein HRCA1, Rat HRCA1 Protein, Rat HRCA1, Rat protein HRCA1, ... Rat Von Hippel Lindau Tumor Suppressor (vHL) is a recombinant Rat protein produced in E. coli using Prokaryotic expression. ...
Membrane-associated MMP regulators: novel cell adhesion tumor suppressor proteins?. Mar 28, 2014. *BibTeX ... Cell Adhesion, Eukaryotic Cells, Matrix Metalloproteinases, Tumor Suppressor Proteins. Abstract. Matrix metalloproteinases are ... enzymes that regulate tissue behavior by interactions with extracellular matrix proteins. RECK, a membrane-anchored inhibitor ... of MMPs was recently characterized for its role in development, tissue homeostasis, and for tumor angiogenesis. ...
Rak Functions as a Tumor Suppressor by Regulating PTEN Protein Stability and Function. In: Cancer Cell. 2009 ; Vol. 15, No. 4. ... Rak Functions as a Tumor Suppressor by Regulating PTEN Protein Stability and Function. Cancer Cell. 2009 Apr 7;15(4):304-314. ... Rak Functions as a Tumor Suppressor by Regulating PTEN Protein Stability and Function. / Yim, Eun Kyoung; Peng, Guang; Dai, Hui ... Therefore, Rak acts as a bona fide tumor suppressor gene through the mechanism of regulating PTEN protein stability and ...
I studied the role of tumor suppressor genes in two syndromes: Birt-Hogg-Dubé (BHD) and von Hippel-Lindau (VHL). BHD is caused ... Germ line mutations in the tumor suppressor von Hippel-Lindau (VHL) gene cause VHL disease, which can lead to the development ... Binding of the VHL protein to hypoxia inducible factors (HIF) leads to their degradation and subsequent suppression of tumor ... Among others, iron regulatory protein 1, peflin and Tumor susceptibility gene 101 were indicated as the most promising ...
... ... Genome-Wide CRISPR Screen Identifies Regulators of Mitogen-Activated Protein Kinase as Suppressors of Liver Tumors in Mice. ...
Tumor Suppressor Protein p53 / genetics* * Xenograft Model Antitumor Assays Substances * Diuretics * TP53 protein, human ...
School of Medicine and Moores Cancer Center report that a signaling protein that normally suppresses tumors can be manipulated ... Signaling Protein Found That Can Act as Tumor Suppressor or Cancer Promoter 2018-03-01 ... At the time, however, it was not clear how the tumor suppressor could turn rogue. In their new work, the team found the culprit ... "Although Daple acts as a tumor suppressor in the healthy colon, the concurrent increased abundance of Daple and epidermal ...
The DCC gene provides instructions for making a protein called the netrin-1 receptor, which is involved in the development of ... tumor suppressor protein DCC. Additional Information & Resources. Tests Listed in the Genetic Testing Registry. *Tests of DCC ... When not bound to netrin-1, the netrin-1 receptor acts as a tumor suppressor, which means that it keeps cells from growing and ... as well as other cancerous tumors. This deletion is not inherited and is found only in the tumor cells. Deletion of the DCC ...
Expression, purification and characterization of the interferon-inducible, antiviral and tumour-suppressor protein, human RNase ... antiviral and tumour-suppressor protein, human RNase L. Journal of Biosciences. 2012 Mar; 37 (1): 103-113. ... which can be utilized to study effects of various agents on the RNase L activity and its protein- protein interactions. ... The optimized expression conditions minimized degradation of the protein, making it a convenient method for purification of ...
The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis. In: Molecular Carcinogenesis. ... The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis. / Virador, Victoria M.; Flores- ... The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis. Molecular Carcinogenesis. 2009 ... Dive into the research topics of The human promyelocytic leukemia protein is a tumor suppressor for murine skin carcinogenesis ...
Tumor Suppressor Proteins / physiology Substances * Chromosomal Proteins, Non-Histone * DNA-Binding Proteins ... and a substantial body of evidence indicates that several components of the SWI/SNF complexes function as tumor suppressors. ...
Nuclear receptor-binding protein 1: a novel tumour suppressor and pseudokinase Jason S. Kerr; Jason S. Kerr ... cancer, nuclear receptor-binding protein 1 (NRBP1), pseudokinase, Ras signalling pathway, tumour-suppressor gene ... Jason S. Kerr, Catherine H. Wilson; Nuclear receptor-binding protein 1: a novel tumour suppressor and pseudokinase. Biochem Soc ... a pseudokinase recently described to have a tumour-suppressive role in cancer, may play in cellular homoeostasis and protein ...
Find quality proteins, antibodies, ELISA kits, laboratory reagents, and tools. ... 3 spontaneous tumors, n. = 2 induced tumors from BrafV600E/Lats1/2−/−. mice). d. Representative IHC of indicated proteins, ... tumors relative to BrafV600E/Pten−/−. tumors. However, sequencing revealed that all tumors from these models were diploid, ... activates the Hippo tumor-suppressor pathway.. a. Representative immunoblot (IB) of dox-inducible BRAFV600E. Mel-ST cells ...
Recent work indicates the LKB1 tumour suppressor protein kinase, which is. * Post author By baxkyardgardener ... Recent work indicates the LKB1 tumour suppressor protein kinase, which is usually mutated in PeutzCJeghers cancer syndrome, ... No Comments on Recent work indicates the LKB1 tumour suppressor protein kinase, which is ... phosphorylates and activates a group of protein kinases that are related to AMPK (AMP-activated protein kinase). domains appear ...
FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 ... and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining ... We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic ... From: Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell carcinoma ...
... upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that ... The level of p53, a tumor suppressor protein, increased notably in a dose-dependent manner. XIAP, AIF, Bax, and Bcl-2 are ... and inactivate major tumor suppressors (p53 and pRB proteins) [2]. Despite the growing availability of HPV vaccines, screening ... It is widely accepted that p53 tumor suppressor proteins are targets of high risk HPV E6 oncoprotein, which binds and ...
Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby ... Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby ... Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby ... which is a known translational suppressor of LASP1 in matched RNA samples revealed an inverse correlation of LASP1 protein and ...
RASSF1A is a tumor suppressor gene that is epigenetically silenced in a wide variety of sporadic human malignancies. Expression ... describe an MST2-dependent effector pathway for RASSF1A proapoptotic signaling and indicate that silencing of RASSF1A in tumors ... Tumor Protein p73, Tumor Suppressor Protein p53, Tumor Suppressor Proteins ... Protein Binding, Protein Transport, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, ...
Sequence feature and expression profile of a tumor suppressor QM protein gene from hard clam Meretrix meretrix Authors. * X Y ... The present study describes the molecular characterization and transcriptional features of a tumor suppressor QM protein gene, ... A ribosomal protein L10 signature, an SH3-binding motif, an antibiotic binding site, an amidation site and two protein kinase C ... The full-length cDNA (819 bp) of MmQM consists of a 657 bp opening reading frame (ORF) encoding a 218 amino acid protein with a ...
Although they do not have obvious mammalian homologs, they are related to LKB1, a tumor suppressor that is mutated in the human ... These results provide the first description of a physiological substrate for the LKB1 tumor suppressor and suggest that it ... Our findings indicate that the tumors in Peutz-Jeghers syndrome could result from deficient activation of AMPK as a consequence ... Recently, we identified three related protein kinases acting upstream of the yeast homolog of AMPK. ...
... higher TMB correlates with favorable response to anti-PD1/PDL1 inhibition in solid tumors). In conclusion, 96.5% of patients ... The median tumor mutational burden (TMB) was low (1.7 alterations/megabase); 12% of patients had intermediate or high TMB ( ... TP53 (Tumor protein p53) is a tumor suppressor; loss leads to overexpression of VEGF levels. Bevacizumab, Pazopanib. Wee-1 inh ... MSH2 (MutS homolog2) is a tumor suppressor encodes DNA mismatch repair (MMR) protein 2. Atezolizumab, Nivolumab Pembrolizumab. ...
Tumor Suppressor Protein p53. Transcription Factor, Sp1. Sp1 Transcription Factor. p14ARF Protein. Tumor Suppressor Protein ... Proto-Oncogene Protein c-met. Proto-Oncogene Proteins c-met. Proto-Oncogene Protein p21(ras). Proto-Oncogene Proteins p21(ras) ... Protein p16. Cyclin-Dependent Kinase Inhibitor p16. Protein p53. ... Heat-Shock Proteins 90. HSP90 Heat-Shock Proteins. I-kappa B. I ... Proto-Oncogene Protein pp60(c-src). Proto-Oncogene Proteins pp60(c-src). ...
A tumor suppressor gene is a gene that reduces the probability that a cell in a multicellular organism will turn into a tumor ... These proteins are known as metastasis suppressors.[2] [3] Examples. The first tumor suppressor protein discovered was the pRb ... Another important tumor suppressor is the p53 tumor suppressor protein produced by the TP53 gene. ... Tumor suppressor genes/proteins. APC - BRCA1 - BRCA2 - CHEK2 - Neurofibromin 1 - Maspin - Neurofibromin 2/Merlin - p14arf - p16 ...
Tumor Suppressor Protein p53. Chimploy K, G Díaz D, Li Q, Carter O, Dashwood W-M, Mathews CK, Williams DE, Bailey GS, Dashwood ... Tumor Cells, Cultured. Wang R, Chen Y-S, Dashwood W-M, Li Q, Löhr CV, Fischer K, Ho E, Williams DE, Dashwood RH. 2017. ... Transcription Factor 7-Like 2 Protein. Dashwood W-M, Orner GA, Dashwood RH. 2002. Inhibition of beta-catenin/Tcf activity by ... NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b] ...
  • I studied the role of tumor suppressor genes in two syndromes: Birt-Hogg-Dubé (BHD) and von Hippel-Lindau (VHL). (uni-goettingen.de)
  • A cascade effect occurs when ras -GTPase is "switched on" by incoming signals, leading to activation of other proteins, which, in turn, activate genes responsible for cell growth and differentiation. (medscape.com)
  • Mutations in ras genes can cause permanent activation of ras proteins. (medscape.com)
  • Unlike oncogenes , tumor suppressor genes generally follow the ' two-hit hypothesis ,' which implies that both alleles that code for a particular gene must be affected before an effect is manifested. (bionity.com)
  • Tumor suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis , and sometimes do both. (bionity.com)
  • 2000. Metastasis-suppressor genes: a review and perspective on an emerging field. (bionity.com)
  • Moreover, ICI-118,551 also impaired the nuclear internalization of HIF-1α in Hemangioblastomas and hypoxic primary endothelial cells, reducing significantly the activation of HIF-target genes and halting the tumour-related angiogenic processes. (nature.com)
  • Genes carry the instructions for making the proteins that control all of your body's activities. (healthline.com)
  • BRCA1 and BRCA2 genes produce a type of protein known as tumor suppressor proteins. (healthline.com)
  • Likewise, hypoxic breast cancer cells showed higher propensity to increase expression of oncogenes and to decrease expression of tumor suppressor genes ( Jefford and Irminger-Finger, 2006 ). (frontiersin.org)
  • The three Proteogenomic Translational Research Centers, created through NCI's Office of Cancer Clinical Proteomics Research , embody the convergence in medicine of information about genes and proteins in an approach known as proteogenomics. (pnnl.gov)
  • Mutations present in these genes result in production of defective proteins unable to do their job, which can result in genetic alterations and ultimately lead to cancer. (nope2bc.com)
  • When not bound to netrin-1, the netrin-1 receptor acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. (medlineplus.gov)
  • Although Daple acts as a tumor suppressor in the healthy colon, the concurrent increased abundance of Daple and epidermal growth factor receptor (EGFR) in colorectal tumors was associated with poor patient prognosis. (medicilon.com)
  • The gene, called PARK2 , encodes a protein that acts as a tumor suppressor. (mskcc.org)
  • These mutations change single protein building blocks (amino acids) in the netrin-1 receptor or introduce a premature stop signal in the instructions for making the protein, resulting in an impaired or missing protein. (medlineplus.gov)
  • Germ line mutations in the tumor suppressor von Hippel-Lindau (VHL) gene cause VHL disease, which can lead to the development of clear cell RCC. (uni-goettingen.de)
  • These observations indicate that tumor suppression mechanisms restrain melanoma development following the acquisition of activating MAPK pathway mutations in melanocytes. (enlibio.com)
  • We also provide evidence the UBA domains do not function as LKB1CSTRAD (STE20-related adaptor)CMO25 (mouse protein 25) docking/interacting sites and that mutations in the UBA website of SIK suppressed the ability of SIK to localize within punctate regions of the nucleus. (baxkyardgardener.com)
  • The adenomatous polyposis coli ( APC ) gene is a tumor suppressor gene, and mutations resulting in loss of APC protein function are associated with carcinogenesis. (cdc.gov)
  • The Hippo name refers to the fact that if mutations in tumor suppressors in this pathway, or expression of the oncogenes, can lead to uncontrolled growth. (wmedicinereport.com)
  • Expression of p63 is almost exclusively restricted to epithelial cells, mutations in this gene are infrequent, and its expression is increased in a variety of solid tumors, particularly those of the head and neck area 12,13 . (bvsalud.org)
  • While the majority of these are frameshift and nonsense mutations that result in a severely truncated and non-functional protein, a minority are point mutations that substitute a single amino acid in the 1,863-amino-acid-long BRCA1 protein. (the-scientist.com)
  • This procedure modeled what happens in humans with BRCA1 mutations, who always carry one good copy of the gene, but who presumably develop tumors from cells that lose the good copy. (the-scientist.com)
  • These mice develop tumors almost as rapidly as mice with null mutations in BRCA1," Baer said, suggesting that the binding of BRCA1 to other phosphorylated proteins is critical for tumor suppression. (the-scientist.com)
  • More than 2,500 tumour genomes of 36 types of cancer were analysed and the team found DNA mutations pointing to one of the two known mechanisms to lengthen telomeres in 13 of the cases . (hilfenetzwerk-cic.de)
  • Hypoxia is a common characteristic of solid tumors ( Bristow and Hill, 2008 ). (frontiersin.org)
  • FA is characterized by bone marrow failure, AML , solid tumors, and developmental abnormalities. (wikipedia.org)
  • This essential process occurs universally in solid tumors secondary to expansion of the cancer mass and subsequent growth away from the existing blood supply. (jnccn.org)
  • The tumor suppressor p53 is a redox-regulated transcription factor involved in cell cycle arrest, apoptosis and senescence in response to multiple forms of stress, as well as many other cellular processes such as DNA repair, glycolysis, autophagy, oxidative stress and differentiation. (warwick.ac.uk)
  • In addition, apoptosis induced by xanthohumol also involves endoplasmic reticulum stress and unfolded protein response. (hindawi.com)
  • RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. (ox.ac.uk)
  • Interacting with various cellular proteins, E6 and E7 influence fundamental cellular functions like cell cycle regulation, telomere maintenance, susceptibility to apoptosis, intercellular adhesion and regulation of immune responses. (info-tecuci.ro)
  • Changes in the levels of cell regulatory proteins were observed thereafter, in particular, Chk2 was activated upon DNA cleavage initiated by the foregoing onset of apoptosis,and this correlated with the S phase cell arrest after 24 hours. (univie.ac.at)
  • The various markers that enable assessment of the progression of preneoplastic lesions to spindle cell carcinoma include the p16 protein, which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). (bvsalud.org)
  • BRCA1 functions in multiple important cellular processes including DNA damage repair, cell cycle checkpoint activation, protein ubiquitination, chromatin remodeling, transcriptional regulation, as well as R-loop formation and apoptosis. (ijbs.com)
  • Although his lab has shown that Nischarin functions as a tumor suppressor, research continues to uncover new information that may lead to better treatments, a news release said. (neworleanscitybusiness.com)
  • In support of this idea are the linea that the colorectal tumor suppressor protein DCC has some structural homology to LAR438 and that the LAR gene maps to a linds on chromosome 1p32-33 that is thought e contain a breast cancer tumor sup- pressor gene. (qrforex.com)
  • Binding of the VHL protein to hypoxia inducible factors (HIF) leads to their degradation and subsequent suppression of tumor growth. (uni-goettingen.de)
  • Downregulation of the HIF2a subunit is necessary and sufficient for tumor growth suppression and thus a promising target for cancer therapy. (uni-goettingen.de)
  • in both conditions, however, the altered gene products have an important role in the dysregulation of tumor suppression. (medscape.com)
  • Researchers have pinpointed the region of a key cancer gene that's involved in tumor suppression. (the-scientist.com)
  • While both the BRCT and RING domains have been implicated in tumor suppression, Columbia University cancer researchers Thomas Ludwig and Richard Baer , who led the current study, wanted to definitively find out if it was the binding of phosphorylated proteins by the BRCT domains, the ubiquitinating capability of the RING domain, or both, which were helping to keep cancer at bay. (the-scientist.com)
  • This study highlights the power of top-down FTICR mass spectrometry for analysis of the cysteine reactivity and redox chemistry in multiple cysteine-containing proteins. (warwick.ac.uk)
  • Using click chemistry, we performed two different isolation methods to later identify candidate proteins through mass spectrometry analysis. (uni-goettingen.de)
  • Recent work indicates the LKB1 tumour suppressor protein kinase, which is usually mutated in PeutzCJeghers cancer syndrome, phosphorylates and activates a group of protein kinases that are related to AMPK (AMP-activated protein kinase). (baxkyardgardener.com)
  • A ribosomal protein L10 signature, an SH3-binding motif, an antibiotic binding site, an amidation site and two protein kinase C phosphorylation sites were revealed from the MmQM sequence. (unimore.it)
  • Here , we report the solution structures of the extended murine PTPN13 PDZ3 domain in its apo form and in complex with its physiological ligand , the carboxy-terminus of protein kinase C-related kinase-2 (PRK2), determined by multidimensional NMR spectroscopy. (ruhr-uni-bochum.de)
  • The aim of our group is to identify PKC (protein kinase C) in vivo function by analysing individual PKC knockouts we have generated over the past few years. (silverchair.com)
  • Palbociclib targets a protein called cyclin-dependent kinase (CDK), a trigger that normally enhances the G1 to S phase, thereby enabling the suppressor gene Rb to act as an inhibitor (see diagram left). (caperay.com)
  • In a new study published today (October 27) in Science , researchers pegged this crucial function to a specific region of the protein known as the BRCT domains: two nearly identical stretches, around 90 amino acids long, that lie toward the carboxyl-end of the protein and are responsible for binding phosphorylated proteins. (the-scientist.com)
  • the BRCT domains in the carboxyl end of the protein, and a region about 110 amino acids long on the opposite end of the protein known as the RING domain. (the-scientist.com)
  • The discovery of cysteine-targeting compounds that cause re-activation of mutant p53 and the death of tumor cells in vivo has emphasised the functional importance of p53 thiols. (warwick.ac.uk)
  • This deletion is not inherited and is found only in the tumor cells. (medlineplus.gov)
  • In this model, reintroduction of wildtype FLCN into FLCN-/- cells, when implanted into immunocompromised mice, showed a significant reduction of tumor growth compared to a comparable transfection of a non-functional exon 5 deletion. (uni-goettingen.de)
  • Building upon earlier work published in 2015, Dr. Ghosh and colleagues investigated a protein called Disheveled-associating protein, or Daple, which is produced by nearly all healthy cells in the body and is well recognized for its role in helping cells in different tissues coordinate processes, such as development and maintenance of organs. (medicilon.com)
  • In their earlier work, the research team reported for the first time that Daple appeared to exert some control over the initiation and progression of colorectal cancer by suppressing tumor formation, but when cells escaped the main tumor and began circulating in the blood stream, the protein made cancer cells more invasive and more likely to spread. (medicilon.com)
  • 2] Ras -GTPase is part of a family of related proteins that are universally expressed in cells and are involved in cellular signal transduction. (medscape.com)
  • Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. (hindawi.com)
  • Their gene products are known to activate telomerase, prevent death of human primary epithelial cells, and inactivate major tumor suppressors (p53 and pRB proteins) [ 2 ]. (hindawi.com)
  • Analysis of published microarray data revealed a significant overexpression of LASP1 in PCa metastases compared to parental primary tumors and normal prostate epithelial cells. (sigmaaldrich.com)
  • Some proteins involved in cell adhesion prevent tumor cells from dispersing, block loss of contact inhibition, and inhibit metastasis . (bionity.com)
  • Collaborative departmental research has revealed that patients who respond to immunotherapy have antibody responses against their tumors and that the presence of B cells within a tumor may serve as a marker to predict patient immunotherapy response. (mdanderson.org)
  • Tumor suppressors prevent the formation of cancerous cells. (mskcc.org)
  • This protein is on the surface of breast cells. (healthline.com)
  • When the HER2 protein is turned on, it tells breast cells to grow and divide. (healthline.com)
  • This causes breast cells to grow uncontrollably and form tumors. (healthline.com)
  • Immunohistochemistry (IHC) tests whether you have too much of the HER2 protein on your cancer cells. (healthline.com)
  • It arises in tissues when oxygen consumption by the cells outpaces supply, due to elevated oxygen demand in metabolically active cells and decreased oxygen transport to the center of the tumor because of inefficient vascularization. (frontiersin.org)
  • The beauty of adding a proteogenomic approach to clinical trials is that by using the patient's own cells and examining thousands of proteins and phosphoproteins for their response to drug treatment, therapy can be truly individualized, and ineffective treatments can be avoided," said Rodland. (pnnl.gov)
  • It is important to emphasize that while the researchers observed cell proliferation-associated changes in the expression of the Ca2+- binding proteins S100A6/A9 following glyphosate exposure to human skin cells, the implications of these findings reach beyond the skin cell lineage. (healthimpactnews.com)
  • In conclusion, in this study, we demonstrated that glyphosate may possibly exert proliferative effect in HaCaT cells by activating Ca2+ binding proteins to promote the imbalance of intracellular Ca2+ homeostasis and lessen SOD1 to increase ROS generation. (healthimpactnews.com)
  • The lab of co-author Dr. Robert Bast Jr., an expert in ovarian cancer and vice president for translational research at MD Anderson, inserted gel-bound carbon nanotubes into the ovaries of rodents to mimic the accumulations that are expected for nanotubes linked to special antibodies that recognize tumor cells. (news-medical.net)
  • The new results suggested that antibody-nanotube probes could potentially detect tumors with as few as 100 ovarian cancer cells, which could make it a valuable tool for early detection. (news-medical.net)
  • Since the pioneering attempts of Denekamp and colleagues in the mid-1970s to sensitize hypoxic tumour cells (Fowler et al. (biomedcentral.com)
  • The result was that the mitochondria in the NF2 cancer cells became dysfunctional upon YAP/TAZ inhibition and produced a lot of oxidative stress that damaged the tumor cells, shrinking them and shutting down growth. (wmedicinereport.com)
  • Over time, however, other signaling pathways come into play that allows tumor cells to rewire their metabolic network to survive the new nutrient conditions, rendering them independent of the YAP/TAZ molecular pathway. (wmedicinereport.com)
  • Cystatin A (Cys A), a cysteine protease inhibitor, is a precursor of proteins involves in keratinocyte keratinization, and is expressed during the late phase of differentiation of these cells. (bvsalud.org)
  • Decrease of interleukin (IL)17a gene expression in leucocytes and in the amount of IL-17a protein in CD4+ T cells in children with Down syndrome. (edu.pl)
  • NETs are a group of tumors with heterogenous malignancy that evolve from neuroendocrine cells, with the lung being the second target organ after the gastrointestinal tract. (spandidos-publications.com)
  • Lung neuroendocrine tumors (LNETs) are a group of rare tumors with heterogenous malignancy originating in amine precursor uptake and decarboxylation (APUD) neuroendocrine cells from Kulchitsky cells (argentaffin cells) ( 1 ). (spandidos-publications.com)
  • The neuroendocrine cells from which neuroendocrine tumors (NETs) derive are located in numerous places in the human body ( 8 ). (spandidos-publications.com)
  • 1 Caveolin-1 is indeed a "tumor suppressor" whose reduction/deletion in cells would provide growth advantages and expedite tumorigenesis. (sputnic-group.ru)
  • Background: Galectin-9 is a member of the family of lectin proteins and crucially regulates human immune responses, particularly because of its ability to suppress the anticancer activities of T lymphocytes and natural killer cells. (diamond.ac.uk)
  • Ehrenwald et al (1994) have claimed that caeruloplasmin containing one redox active copper per protein molecule can oxidize LDL in the presence of cells. (letswheelthewheels.com)
  • Cells depend on their DNA for coding information to make various classes of proteins that include enzymes, certain hormones, transport proteins, and structural proteins that support life. (cdc.gov)
  • The synthetic mRNA material, wrapped in an oily bubble coating made of lipid nanoparticles, delivers instructions to cells to make spike proteins to fight the virus. (swfinstitute.org)
  • When synthetic mRNA enters the human patient, the material fuses to cells and cell's molecules start to decode the genomic sequence to build the spike proteins. (swfinstitute.org)
  • Rat Von Hippel Lindau Tumor Suppressor (vHL) is a recombinant Rat protein produced in E. coli using Prokaryotic expression. (abbexa.com)
  • Expression of the PTEN tumor suppressor is frequently lost in breast cancer in the absence of mutation or promoter methylation through as yet undetermined mechanisms. (elsevier.com)
  • Notably, ectopic expression of Rak effectively suppressed breast cancer cell proliferation, invasion, and colony formation in vitro and tumor growth in vivo. (elsevier.com)
  • Small molecules inhibiting translation of HIF2a as chemical biology probes were used to identify proteins that regulate HIF expression and therefore may be involved in initiation and/or progression of RCC. (uni-goettingen.de)
  • Expression of the PMLRARα fusion dominant-negative oncogene in the epidermis of transgenic mice resulted in spontaneous skin tumors attributed to changes in both the PML and RAR pathways [Hansen et al. (elsevier.com)
  • Conversely, qRT-PCR analyses for mir-203, which is a known translational suppressor of LASP1 in matched RNA samples revealed an inverse correlation of LASP1 protein and mir-203 expression. (sigmaaldrich.com)
  • 2003. Mutational analysis of Ctnnb1 and Apc in tumors from rats given 1,2-dimethylhydrazine or 2-amino-3-methylimidazo[4,5-f]quinoline: mutational 'hotspots' and the relative expression of beta-catenin and c-jun. . (oregonstate.edu)
  • ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. (nih.gov)
  • Changes in the expression of the Ca2+- binding family of proteins (S100 family) S100A6/S100A9, associated with various cancers. (healthimpactnews.com)
  • MicroRNAs (miRNAs) are endogenously synthesized small non-coding RNAs that regulate gene expression by interfering with protein translational machinery and/or inducing degradation of target mRNAs [ 1 ]. (cdc.gov)
  • This mature miRNA is bound by the RISC complex, guiding it to the 3'UTR of target mRNAs, leading to repression of protein expression. (cdc.gov)
  • Interestingly, reduced binding of exportin-5 by reduction of the protein itself or alteration in the miRNA structure causes a reduced expression of the mature miRNA, without buildup of pre-miRNA in the nucleus [ 5 ]. (cdc.gov)
  • These in vitro, and their expression in these human tumour virus. (who.int)
  • Doing so, we have started to investigate PKC expression profiles under various tumour conditions in mice. (silverchair.com)
  • Members of this family of proteins are often found associated with histone-modifying enzymes and protein complexes that regulate gene expression. (musc.edu)
  • microRNAs are small non-protein-coding RNA molecules that regulate gene expression, and have a potential epigenetic role in disease progression and survival of colorectal cancer. (biomedcentral.com)
  • In terms of tumor-normal expression differences, many microRNAs exhibit evidence of being up-regulated in some subjects but down-regulated in others, or are dysregulated only for a subset of the population. (biomedcentral.com)
  • We present and implement an approach to identify factors (lifestyle, tumor molecular phenotype, and survival-related) that are associated with the direction and/or significance of these microRNAs' tumor-normal expression differences in colorectal cancer. (biomedcentral.com)
  • Using expression data for 1394 microRNAs and 1836 colorectal cancer subjects (each with both tumor and normal samples), we perform a dip test to identify microRNAs with multimodal distributions of tumor-normal expression differences. (biomedcentral.com)
  • For proximal, distal, and rectal tumor sites separately, these microRNAs are tested for tumor-normal differential expression using a signed rank test, both overall and within levels of each lifestyle, tumor molecular phenotype, and survival-related factor. (biomedcentral.com)
  • We identify hundreds of microRNAs whose direction and/or significance of tumor-normal differential expression is associated with one or more lifestyle, tumor molecular phenotype, or survival-related factors. (biomedcentral.com)
  • The results of this study demonstrate the benefit to colorectal cancer researchers to consider multiple subject-level factors when studying dysregulation of microRNAs, whose tumor-related changes in expression can be associated with multiple factors. (biomedcentral.com)
  • Our results will serve as a publicly-available resource to provide clarifying information about various factors associated with the direction and significance of tumor-normal differential expression of microRNAs in colorectal cancer. (biomedcentral.com)
  • Considering additional factors beyond the tumor/normal distinction allows for greater specificity in conclusions regarding differential expression, as microRNA expression seems to be quite dynamic. (biomedcentral.com)
  • SCOPe: Structural Classification of Proteins - extended. (berkeley.edu)
  • Labeling of RGD peptides with near-infrared fluorophores yields optical probes for noninvasive imaging of tumors overexpressing alpha-v-beta3 integrins. (cipsm.de)
  • Overexpression of DAB2IP's rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR-431's effect on promoting invasion, Erk phosphorylation, and epithelial-mesenchymal transition of PNETs. (ox.ac.uk)
  • The p63 protein, a homologue of p53, may be associated with tumor formation in the epithelial tissue, acting as an oncogene 11,12 . (bvsalud.org)
  • Given the highly penetrant nature of NF1, individuals who have an altered NF1 gene will eventually present with some clinical feature of this neurocutaneous syndrome and are at an increased risk of developing benign and/or malignant tumors. (medscape.com)
  • Benign tumors seen in persons with NF1 include cutaneous neurofibromas, plexiform neurofibromas, and optic nerve gliomas. (medscape.com)
  • [ 4 , 5 ] ) Benign neoplasms occur more frequently in women than in men, but malignant tumors are distributed equally between the sexes. (medscape.com)
  • Most tumors (65%) are benign, with hemangiomas being the most common, followed by pleomorphic adenomas. (medscape.com)
  • Schwartz CJ, Schandl CA, Morse J, Ralston J, Rapkiewicz A, Darvishian F. Benign Fibromyxoid Lesion of the Breast: A Distinct Entity From Benign Spindle Cell Tumors of the Mammary Stroma? (musc.edu)
  • YAP and TAZ are part of the "Hippo" signaling pathway, which includes both tumor suppressors and oncogenes. (wmedicinereport.com)
  • The incidence of pancreatic neuroendocrine tumor (PNET) is increasing, and it presents with various clinical manifestations and an unfavorable survival rate. (ox.ac.uk)
  • Chinese cabbage powder effectively reduced the incidence of liver tumour induced by aflatoxin B1 from 6.67% to 0% in animals. (greenmedinfo.com)
  • For other human tumour virus- primate species are related to the hu- tween data in humans and in experi- es, the use of humanized severe man tumour viruses, the incidence of mental animals is not obvious. (who.int)
  • That is, as the size of the gland decreases, the incidence of malignancy of a tumor in the gland increases in approximately these proportions. (medscape.com)
  • These rare tumors are usually asymptomatic and non‑functional with little information regarding incidence in the specialty literature. (spandidos-publications.com)
  • This review shows that the Arab World is considered a low-rate GC incidence region, presenting almost the same tumour characteristics as the Western countries. (who.int)
  • Although researchers have learned much from the study of this diverse group of tumors over the years, the diagnosis and treatment of salivary gland neoplasms remain complex and challenging problems for the head and neck surgeon. (medscape.com)
  • Combined types of LNETs remain a controversial topic of discussion regarding diagnosis and treatment, a topic on which further studies are required in order to improve diagnosis in this group of tumors with heterogenous malignancy. (spandidos-publications.com)
  • There is a clear consensus in studies in which tumor genomes have been sequenced and analyzed that hypoxia is associated with tumor genomic instability. (frontiersin.org)
  • The combination of proteomic, transcriptomic, and genomic data can now reproducibly identify proteins in cancer genomes that were difficult or not possible to infer by genomics alone," said Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research of the National Cancer Institute. (pnnl.gov)
  • Membrane-associated MMP regulators: novel cell adhesion tumor suppressor proteins? (ucsf.edu)
  • We developed two reversible F2H assays for the interactions between the tumor suppressor p53 and its negative regulators, Mdm2 and Mdm4. (ncl.ac.uk)
  • Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor tyrosine kinases (RTKs), and heterotrimeric G proteins and associated GPCRs [G-protein-coupled receptors]. (medicilon.com)
  • Here we utilize cell and murine models to demonstrate that oncogenic BRAF leads to activation of the Hippo tumor suppressor pathway, both in melanocytes in vitro and nevus melanocytes in vivo. (enlibio.com)
  • One exception is hu- humanized SCID mice, the use of al oncogenic viruses that are strictly man T-cell lymphotropic virus type 1 surrogate hosts has not proven very species-specific, causing cancer in (HTLV-1): in addition to its ability to useful for defining tumour site con- humans only. (who.int)
  • YAP and TAZ proteins are oncogenic, and in some tumors, one or the other, or both, are over-expressed. (wmedicinereport.com)
  • Many of the proteins that interact with, transcriptionally repress, or are inhibited by Caveolin-1 fall under the pro-proliferative, oncogenic, and anti-apoptotic category of molecules. (sputnic-group.ru)
  • Scientists at the University of California San Diego (UCSD) School of Medicine and Moores Cancer Center report that a signaling protein that normally suppresses tumors can be manipulated (or reprogrammed) by growth factors, turning it into a driver of malignant growth and metastasis. (medicilon.com)
  • These findings identify a cross-talk paradigm among growth factor RTKs, heterotrimeric G proteins, and the Wnt/FZD pathway in cancer. (medicilon.com)
  • The present review discusses the interactions and potential functions that nuclear receptor-binding protein 1, a pseudokinase recently described to have a tumour-suppressive role in cancer, may play in cellular homoeostasis and protein regulation. (silverchair.com)
  • Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration. (sigmaaldrich.com)
  • Several studies have linked overexpression of the LIM and SH3 domain protein 1 (LASP1) to progression of breast, colon, liver, and bladder cancer. (sigmaaldrich.com)
  • Since Wip1 has been shown to be amplified in tumors, we are developing specific inhibitors of its activity that would provide selective targeting either when given alone or in combination with standard cancer chemo- or radio-therapy. (cancer.gov)
  • Inactivation of p53 is present in almost every tumor, and hence, p53-reactivation strategies are an important aspect of cancer therapy. (jbc.org)
  • One of the major consequences of the lack of a functional VHL protein in von Hippel-Lindau disease, a rare cancer, is the constitutive activation of the HIF pathway. (nature.com)
  • As a common characteristic of cancer, hypoxia is associated with poor prognosis due to enhanced tumor malignancy and therapeutic resistance. (frontiersin.org)
  • Therefore, a clear understanding of how tumor hypoxia induces genomic instability is crucial for the improvement of cancer therapeutics. (frontiersin.org)
  • The drug Cilengitide, c(RGDf(NMe)V), is a cyclic RGD pentapeptide (R=arginine, D=aspartic acid, G=glycine) currently in clinical phase III for the treatment of brain tumors and in phase II for other cancer types. (cipsm.de)
  • Karin Rodland heads a PNNL team contributing crucial knowledge about proteins in studies of cancer patients. (pnnl.gov)
  • RICHLAND, Wash. - The Department of Energy's Pacific Northwest National Laboratory is part of a nationwide effort to learn more about the role of proteins in cancer biology and to use that information to benefit cancer patients. (pnnl.gov)
  • PNNL is paired with physicians and scientists at Oregon Health & Science University in one of three projects announced this week by the National Cancer Institute to bring detailed data about proteins to the bedsides of participants in current clinical trials. (pnnl.gov)
  • Last year, in a study published in Cell, Rodland and colleagues took at in-depth look at the proteins in the tumors of 169 ovarian cancer patients, marking one of the biggest studies ever done in proteogenomics. (pnnl.gov)
  • A Proteome Characterization Center headed by PNNL scientists Tao Liu and Richard D. Smith, which is focusing on the proteins involved in uterine cancer. (pnnl.gov)
  • We envision that PTRCs will collaborate with NCI-sponsored clinical trials to expand/deepen our knowledge of drug response and resistance, ultimately improving our understanding of the cancer and the tumor proteome. (pnnl.gov)
  • Researchers at Rice University and the University of Texas MD Anderson Cancer Center have refined and, for the first time, run in vivo tests of a method that may allow nanotube-based probes to locate specific tumors in the body. (news-medical.net)
  • Their ability to pinpoint tumors with submillimeter accuracy could eventually improve early detection and treatment of ovarian cancer. (news-medical.net)
  • He said more refined versions of the optical scanner may then be able to locate a tumor within seconds, and further advances may extend the method's application to human cancer detection. (news-medical.net)
  • Animal models for human tumour mental animals is not easy to answer does induce adult T-cell leukaemia/ viruses that make use of animal virus- for these agents, because cancer bi- lymphoma (ATLL), albeit in monkeys es are scarce. (who.int)
  • In this advanced age of molecular sleuthing, a research team led by Georgetown Lombardi Comprehensive Cancer Center have findings that suggest tumors will eventually become resistant to drug inhibitors of a common cancer pathway (dubbed YAP/TAZ), now in preclinical development. (wmedicinereport.com)
  • LSU Health New Orleans says research led by one of its professors has found a new role for a protein in preventing the growth and spread of breast cancer. (neworleanscitybusiness.com)
  • Suresh Alahari, professor of biochemistry and molecular biology at LSU Health New Orleans School of Medicine, discovered the protein, Nischarin, which is involved in regulating breast cancer cell migration and movement. (neworleanscitybusiness.com)
  • The discovery of the blockbuster tumor suppressor gene breast cancer 1, early onset ( BRCA1 ) in the early 1990s was a major breakthrough in unraveling the genetics of common hereditary cancers such as breast and ovarian. (the-scientist.com)
  • Breast cancer susceptibility gene 1 ( BRCA1 ) encodes a tumor suppressor that is frequently mutated in familial breast and ovarian cancer patients. (ijbs.com)
  • The first description of carcinoid tumors belongs to Siegfried Oberndorfer who considered these tumors to have a slow growth, being cancer-like tumors ( 2 ). (spandidos-publications.com)
  • At a cancer meeting in San Diego earlier this year, oncologist Richard Finn showed that in 165 women with metastatic breast cancer, patients on the drug experienced no new tumour growth for an extra 10 months. (caperay.com)
  • Tumor-Derived Extracellular Vesicles Predict Clinical Outcomes in Oligometastatic Prostate Cancer and Suppress Antitumor Immunity. (mayo.edu)
  • This work has the goal of identifying such cases where factors of interest are associated with the direction and significance of microRNA tumor-normal dysregulation in colorectal cancer subjects. (biomedcentral.com)
  • Thus, the Daple-dependent activation of G αi and the Daple-dependent enhancement of β-catenin-independent Wnt signals are not only stimulated by Wnt5a/FZD7 to suppress tumorigenesis but also hijacked by growth factor-activated RTKs to enhance tumor progression. (medicilon.com)
  • The human p53 tumor suppressor protein is centrally involved in multiple processes that reduce both the initiation of tumors and their progression. (cancer.gov)
  • Conclusion: p63, p16, MIB, Cal A, Cys A are markedly expressed and p16 is strongly suppressed in oral cavity tumors, which suggests that the latter protein may play a role in negative regulation of cell cycle progression. (bvsalud.org)
  • In order to prove this hypothesis, we then crossed relevant PKC knockout lines on the appropriate tumour background and analysed tumour growth and progression under PKC-deficient conditions. (silverchair.com)
  • The latter is known to bind to the protein BARD1 (BRCA1-associated RING domain protein 1) and form a complex that helps attach ubiquitin to proteins. (the-scientist.com)
  • While this mutation still allowed BRCA1 to bind to BARD1 (which is necessary for the stability of both proteins), it impaired the complex's enzymatic ability to ubiquitinate. (the-scientist.com)
  • In contrast, mice with a mutation that grossly deforms BRCA1 develop tumors 15 months after their good BRCA1 copy is deleted. (the-scientist.com)
  • But mice with a point mutation in the BRCT domain, which impaired BRCA1's ability to bind the phosphate group of phosphorylated proteins, did develop tumors in the mammary glands and the pancreas after the wildtype BRCA1 allele was knocked down. (the-scientist.com)
  • Furthermore, we assessed the specificity of these antibodies to detect mouse BRCA1 protein through the use of testis tissue and mouse embryonic fibroblasts (MEFs) from Brca1 +/+ and Brca1 Δ11/Δ11 mice. (ijbs.com)
  • Deletions of genetic material that include the DCC gene have been found in more than 70 percent of colorectal cancers, as well as other cancerous tumors. (medlineplus.gov)
  • But important, complementary information comes from proteins - the molecular workhorses that actually implement the genetic instructions in the body. (pnnl.gov)
  • FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination . (wikipedia.org)
  • The researchers previously reported on glyphosate's tumor promoting potential in a two-stage mouse skin carcinogenesis model [i] through its disruption of proteins that regulate calcium (Ca 2 +- ) signaling and oxidative stress (SOD 1), but were unable in these investigations to identify the exact molecular mechanisms behind how glyphosate contributes to tumor promotion . (healthimpactnews.com)
  • Neuroendocrine tumors (NETs) can have multiple localizations in the human body however, most often, it appears in the in thorax at tracheobronchial tree and the thymus. (spandidos-publications.com)
  • The main purpose of this review, was the analysis of the available literature in all aspects while mainly focusing on molecular diagnosis data and secondly, by using this molecular landscape to establish a differentiation of lung neuroendocrine tumors (LNETs). (spandidos-publications.com)
  • To determine the contribution of PML to skin tumor susceptibility, transgenic mice were generated on an FVB/N background, that overexpressed the human PML protein in epidermis and hair follicles under the control of the bovine keratin 5 promoter. (elsevier.com)
  • Following skin tumor induction with 7, 12-dimethylbenz[a] anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter, papilloma multiplicity and size were decreased in the transgenic mice by 35%, and the conversion of papillomas to carcinomas was delayed. (elsevier.com)
  • Exemplary of this approach, recent data generated with PKCα-deficient APC Min (adenomatous polyposis coli) mice identify PKCα in this system acting as a tumour suppressor instead of being a promoter as suggested from PMA data. (silverchair.com)
  • Dr. Appella was among the first researchers to identify the tumor suppressor protein p53, and he has studied its roles in the cell and regulation by post-translational modification. (cancer.gov)
  • The molecular mechanisms that govern p53-dependent cell fate decisions are incompletely understood but are believed to be largely mediated by multiple post-translational modifications to p53 itself as well as to other proteins with which p53 interacts. (cancer.gov)
  • We are using biophysical, biochemical, and structural methods to explore the modulation of p53 protein-protein interactions by post-translational modifications. (cancer.gov)
  • Our results show that the protein is not completely random coil but adopts a compact structure consisting of transient long-range contacts, which is regulated by post-translational phosphorylation. (ruhr-uni-bochum.de)
  • However, to date, there is no clinical trial as such testing the role of plant phenolic compounds for inhibiting tumor growth in humans. (biomedcentral.com)
  • For this reason, the infect humans, this virus can infect cordance between humans and ex- question about tumour site concor- several other species - including perimental animals. (who.int)
  • Matrix metalloproteinases are enzymes that regulate tissue behavior by interactions with extracellular matrix proteins. (ucsf.edu)
  • RECK, a membrane-anchored inhibitor of MMPs was recently characterized for its role in development, tissue homeostasis, and for tumor angiogenesis. (ucsf.edu)
  • Central to the development of novel clinic approaches is improvement in the differential responses between normal and tumour tissue at a fixed dose, termed the therapeutic ratio. (biomedcentral.com)
  • Archival tumour tissue blocks, if possible, were collected at phase II trial of capecitabine plus RAD001 in 47 refractory GC patients (at clinicaltrials.gov NCT#01099527). (jcancer.org)
  • For example, rather than simply concluding that a given microRNA is significantly dysregulated in tumor compared to normal tissue, we can identify sub-groups of subjects (corresponding to levels of a particular factor) where the dysregulation is no longer significant or even changes direction - with the microRNA tending to be up-regulated in one sub-group but down-regulated in another. (biomedcentral.com)
  • APC protein down-regulates the Wnt signaling pathway through its binding to β-catenin and axin ( 8 ). (cdc.gov)
  • The YAP/TAZ pathway is known to act as central players in growth, survival, and spread of a number of tumors-such as breast, colorectal, liver, pancreatic and kidney cancers. (wmedicinereport.com)
  • Recent evidence demonstrated that galectin-9 is highly expressed in a wide range of human malignancies including the most aggressive tumors, such as high-grade glioblastomas and pancreatic ductal adenocarcinomas, as well as common malignancies such as breast, lung and colorectal cancers. (diamond.ac.uk)
  • Our study supports the benefit that YAP/TAZ inhibitors may initially offer benefit in treating a wide variety of tumors, but by drilling deep into how they would work, we also found a potential way to extend their benefit to patients," says the study's senior investigator, Chunling Yi, Ph.D., associate professor in the Tumor Biology Program at Georgetown Lombardi. (wmedicinereport.com)
  • Occupational exposure limits with proteins such as topoisomerase inhibitors, and mitotic and meiotic spindle poisons. (cdc.gov)
  • Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. (embl.de)
  • A DNA-binding protein that contains an N-terminal BTB (POZ) DOMAIN and C-terminal CYS2-HIS2 ZINC FINGERS . (nih.gov)
  • contains a zinc finger,XV" YOL091W 1 15 16 YOL091W "involved in sporulation,XV" YOL103W-B 1 15 17 YOL103W-B "TyB Gag-Pol protein. (davidson.edu)
  • In lanes 5 and 7 some immunoglobulin heavy chain (IgG-H) had eluted from the protein G-Sepharose despite the fact that it had been cross-linked: this explains why LKB1 may not appear to comigrate in lanes 1, 5 and 7. (biomedcentral.com)
  • 2011. NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). . (oregonstate.edu)
  • To wit, a member of Hippo pathway, Merlin/NF2, is a tumor suppressor which, when mutated, leads to development of some kidney cancers as well as the inherited syndrome neurofibromatosis type 2 (NF2), a nervous system tumor syndrome that mainly afflicts children. (wmedicinereport.com)
  • RASSF1A is a tumor suppressor gene that is epigenetically silenced in a wide variety of sporadic human malignancies. (ox.ac.uk)
  • This phosphatase, Wip1 (PPM1D), is amplified or overexpressed in several human tumors. (cancer.gov)
  • The study, published in the December issue of Nature Genetics , was led by physician-scientist Timothy A. Chan, a radiation oncologist and member of the Human Oncology and Pathogenesis Program and the Brain Tumor Center . (mskcc.org)
  • Human epidermal growth factor receptor 2 (HER2) codes for the production of the receptor protein HER2. (healthline.com)
  • Moreover, The use of animals as surrogate rine host, can provide a platform for animal models for tumour viruses in hosts for the study of human tu- in vivo infection. (who.int)
  • BHD is caused by a germline mutation of the tumor suppressor gene folliculin (FLCN). (uni-goettingen.de)
  • A mutation or deletion of such a gene will increase the probability of the formation of a tumor. (bionity.com)
  • Patients with VHL disease harbour a single mutation allele in the tumour suppressor gene VHL (3p25-p26). (nature.com)
  • This review summarizes recent developments highlighting the association of tumor hypoxia with genomic instability and the mechanisms by which tumor hypoxia drives genomic instability, followed by how hypoxic tumors can be specifically targeted to maximize efficacy. (frontiersin.org)
  • Specialized cell structures called ribosomes are the cellular organelles that actually synthesize the proteins (RNA transcription). (cdc.gov)
  • At the ribosome, the processed mRNA is translated to produce proteins from amino acid units. (cdc.gov)
  • These proteins are known as metastasis suppressors. (bionity.com)
  • Among others, iron regulatory protein 1, peflin and Tumor susceptibility gene 101 were indicated as the most promising candidate target proteins by these methods. (uni-goettingen.de)
  • Protein tyrosine phosphatase PTPN13, also known as PTP-BL in mice, is a large multi-domain non-transmembrane scaffolding protein with a molecular mass of 270 kDa. (ruhr-uni-bochum.de)
  • Protein tyrosine phosphatase PTPN13, also known as PTP-BL in mice, represents a large multi-domain non-transmembrane scaffolding protein that contains five consecutive PDZ domains. (ruhr-uni-bochum.de)
  • Salivary gland neoplasms make up 6% of all head and neck tumors. (medscape.com)
  • Docking-dependent ubiquitination of the interferon regulatory factor-1 tumor suppressor protein by the ubiquitin ligase CHIP. (genefrontier.com)
  • We have also examined how mono- or di-methylation of a specific lysine residue in the C-terminal regulatory domain of p53 respectively represses or activates p53 activity through modulation of the interaction of p53 with specific proteins. (cancer.gov)
  • In addition, DNA methyltransferase 3A (DNMT3A) activity is modulated by several regulatory proteins, including p53 and thymine DNA glycosylase (TDG). (jbc.org)
  • However, the relative role of histone tails and regulatory proteins in the simultaneous coordination of DNMT3A activity remains obscure. (jbc.org)
  • A family of endogenous regulatory proteins that associate with RETINOBLASTOMA PROTEIN via a specific high-affinity binding domain. (musc.edu)
  • The PSD-95 family of scaffold proteins plays a prominent role in coordinating and regulating synaptic function. (jneurosci.org)
  • The PSD-95 family of postsynaptic scaffolding proteins, in addition to organizing postsynaptic components at glutamate synapses, acts transcellularly to regulate synchronous glutamate release. (jneurosci.org)
  • The present study describes the molecular characterization and transcriptional features of a tumor suppressor QM protein gene, MmQM , in Meretrix meretrix . (unimore.it)
  • The full-length cDNA (819 bp) of MmQM consists of a 657 bp opening reading frame (ORF) encoding a 218 amino acid protein with a calculated molecular mass of 25.3 kDa and theoretical isoelectric point of 10.2. (unimore.it)
  • Rapid blood and lymphatic spread and breast tumor emboli are the main features ofIBC 4 . (bvsalud.org)
  • Knockdown of Rak enhanced the binding of PTEN to its E3 ligase NEDD4-1 and promoted PTEN polyubiquitination, leading to PTEN protein degradation. (elsevier.com)
  • Therefore, Rak acts as a bona fide tumor suppressor gene through the mechanism of regulating PTEN protein stability and function. (elsevier.com)
  • Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor. (mdm2signaling.com)
  • Retinoblastoma Binding Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (musc.edu)
  • This graph shows the total number of publications written about "Retinoblastoma Binding Proteins" by people in this website by year, and whether "Retinoblastoma Binding Proteins" was a major or minor topic of these publications. (musc.edu)
  • Below are the most recent publications written about "Retinoblastoma Binding Proteins" by people in Profiles. (musc.edu)