Proteins found mainly in icosahedral DNA and RNA viruses. They consist of proteins directly associated with the nucleic acid inside the NUCLEOCAPSID.
A nucleocytoplasmic transport protein that binds to ALPHA KARYOPHERINS and RAN GTP BINDING PROTEIN inside the CELL NUCLEUS and participates in their export into CYTOPLASM. It is also associated with the regulation of APOPTOSIS and microtubule assembly.
Species of the genus MASTADENOVIRUS, causing a wide range of diseases in humans. Infections are mostly asymptomatic, but can be associated with diseases of the respiratory, ocular, and gastrointestinal systems. Serotypes (named with Arabic numbers) have been grouped into species designated Human adenovirus A-F.
Transforming proteins coded by sis oncogenes. Transformation of cells by v-sis is related to its interaction with the PDGF receptor and also its ability to alter other transcription factors.
The GENETIC TRANSLATION product from a GENE FUSION between a sequence from the tpr protein gene on the human CHROMOSOME 1 and the gene for PROTO-ONCOGENE PROTEINS C-MET.
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.
An oncogene protein that was originally isolated from a spontaneous musculo-aponeurotic FIBROSARCOMA in CHICKEN and shown to be the transforming gene of the avian retrovirus AS42. It is a basic leucine zipper TRANSCRIPTION FACTOR and the founding member of the MAF TRANSCRIPTION FACTORS.
Transforming glycoprotein coded by the fms oncogene from the Susan McDonough strain of feline sarcoma virus (SM-FeSV). The oncogene protein v-fms lacks sequences, which, in the highly homologous proto-oncogene protein c-fms (CSF-1 receptor), normally serve to regulate its tyrosine kinase activity. The missing sequences in v-fms mimic the effect of ligand and lead to constitutive cell growth. The protein gp120(v-fms) is post-translationally modified to generate gp140(v-fms).
A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.
Transforming proteins coded by mos oncogenes. The v-mos proteins were originally isolated from the Moloney murine sarcoma virus (Mo-MSV).
Transforming protein coded by myc oncogenes. The v-myc protein has been found in several replication-defective avian retrovirus isolates which induce a broad spectrum of malignancies.
A family of transforming proteins isolated from retroviruses such as MOUSE SARCOMA VIRUSES. They are viral-derived members of the raf-kinase family of serine-theonine kinases.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Transforming protein coded by jun oncogenes (GENES, JUN). This is a gag-onc fusion protein of about 65 kDa derived from avian sarcoma virus. v-jun lacks a negative regulatory domain that regulates transcription in c-jun.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A cell line derived from cultured tumor cells.
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.
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.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
Transforming proteins coded by fos oncogenes. These proteins have been found in the Finkel-Biskis-Jinkins (FBJ-MSV) and Finkel-Biskis-Reilly (FBR-MSV) murine sarcoma viruses which induce osteogenic sarcomas in mice. The FBJ-MSV v-fos gene encodes a p55-kDa protein and the FBR-MSV v-fos gene encodes a p75-kDa fusion protein.
A signal transducing adaptor protein that is encoded by the crk ONCOGENE from TYPE C AVIAN RETROVIRUSES. It contains SRC HOMOLOGY DOMAINS and is closely related to its cellular homolog, PROTO-ONCOGENE PROTEIN C-CRK.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
Transforming proteins coded by myb oncogenes. Transformation of cells by v-myb in conjunction with v-ets is seen in the avian E26 leukemia virus.
An oncoprotein from the Cas NS-1 murine retrovirus that induces pre- B-CELL LYMPHOMA and MYELOID LEUKEMIAS. v-cbl protein is a tyrosine-phosphorylated, truncated form of its cellular homologue, PROTO-ONCOGENE PROTEIN C-CBL.
Transforming proteins encoded by erbB oncogenes from the avian erythroblastosis virus. The protein is a truncated form of the EGF receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) whose kinase domain is constitutively activated by deletion of the ligand-binding domain.
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.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
Transforming proteins coded by rel oncogenes. The v-rel protein competes with rel-related proteins and probably transforms cells by acting as a dominant negative version of c-rel. This results in the induction of a broad range of leukemias and lymphomas.
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.
Transforming proteins encoded by erbA oncogenes from the avian erythroblastosis virus. They are truncated versions of c-erbA, the thyroid hormone receptor (RECEPTORS, THYROID HORMONE) that have retained both the DNA-binding and hormone-binding domains. Mutations in the hormone-binding domains abolish the transcriptional activation function. v-erbA acts as a dominant repressor of c-erbA, inducing transformation by disinhibiting proliferation.
Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 3.6.1.47.
Established cell cultures that have the potential to propagate indefinitely.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
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.
A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
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.
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.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
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.
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.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A tyrosine-specific protein kinase encoded by the v-src oncogene of ROUS SARCOMA VIRUS. The transforming activity of pp60(v-src) depends on both the lack of a critical carboxy-terminal tyrosine phosphorylation site at position 527, and the attachment of pp60(v-src) to the plasma membrane which is accomplished by myristylation of its N-terminal glycine.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
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.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
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.
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.
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Products of viral oncogenes, most commonly retroviral oncogenes. They usually have transforming and often protein kinase activities.
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 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.
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.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
A viral oncoprotein originally isolated from a murine T CELL LYMPHOMA infected with the acutely transforming retrovirus AKT8. v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Elements of limited time intervals, contributing to particular results or situations.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
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.
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 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
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.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
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.
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.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
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.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
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.
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
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.
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.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
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 raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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 short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.
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 biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Glycoproteins found on the membrane or surface of cells.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Transport proteins that carry specific substances in the blood or across cell membranes.
A ubiquitously found basic protein that binds to phosphatidylethanolamine and NUCLEOTIDES. It is an endogenous inhibitor of RAF KINASES and may play a role in regulating SIGNAL TRANSDUCTION. Phosphatidylethanolamine-binding protein is the precursor of hippocampal cholinergic neurostimulating peptide, which is cleaved from the N-terminal region of the protein.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
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.
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.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
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.
The action of a drug in promoting or enhancing the effectiveness of another drug.
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)
Proteins prepared by recombinant DNA technology.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
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.
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.
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.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
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).
Tumors or cancer of the human BREAST.
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.
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.
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
Agents that inhibit PROTEIN KINASES.
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.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
DNA present in neoplastic tissue.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its caspase recruitment domain with CARD SIGNALING ADAPTOR PROTEINS. Caspase 2 plays a role in APOPTOSIS by cleaving and activating effector pro-caspases. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
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.
An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Tumors or cancer of the COLON.
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
CULTURE MEDIA free of serum proteins but including the minimal essential substances required for cell growth. This type of medium avoids the presence of extraneous substances that may affect cell proliferation or unwanted activation of cells.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.
Tumors or cancer of the LUNG.
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.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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/)
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
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 group of phenyl benzopyrans named for having structures like FLAVONES.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Subsequent experiments showed that the normal, cellular Raf genes can also mutate to become oncogenes, by "overdriving" MEK1/2 ... "Protein phosphatases 1 and 2A promote Raf-1 activation by regulating 14-3-3 interactions". Oncogene. 20 (30): 3949-58. doi: ... Chen J, Fujii K, Zhang L, Roberts T, Fu H (July 2001). "Raf-1 promotes cell survival by antagonizing apoptosis signal- ... RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an ...
Abl gene Androgen receptor Apoptosis-antagonizing transcription factor ARID4A Aryl hydrocarbon receptor BRCA1 BRF1 C-jun C-Raf ... cloning and characterization of a cellular p53 binding protein that interacts with Rb". Oncogene. 14 (2): 145-55. doi:10.1038/ ... prevents induction of cellular senescence, promotes angiogenesis, and increases metastatic potential. Although most cancers ... The retinoblastoma protein (protein name abbreviated Rb; gene name abbreviated RB or RB1) is a tumor suppressor protein that is ...
Trastuzumab targets tumor cells and causes apoptosis through the immune system by promoting antibody-dependent cellular ... is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. ... The Ras-Raf-MAPK pathway is a major signalling route for the ErbB family, as is the PI3-K/AKT pathway, both of which lead to ... The ErbB protein family consists of 4 members ErbB-1, also named epidermal growth factor receptor (EGFR) ErbB-2, also named ...
AKT - the AKT family of proteins AKT2 - the gene for the second member of the AKT family AKT3 - the gene for the third member ... Remy I, Michnick SW (Feb 2004). "Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt". Mol. ... "Entrez Gene: AKT1 v-akt murine thymoma viral oncogene homolog 1". Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters ... Zimmermann S, Moelling K (Nov 1999). "Phosphorylation and regulation of Raf by Akt (protein kinase B)". Science. 286 (5445): ...
... normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting ... Downstream effectors of Ras include three mitogen-activated protein kinases Raf a MAP Kinase Kinase Kinase (MAPKKK), MEK a MAP ... "the cellular origin of retroviral oncogenes".] Press Release. Shih, C; Weinberg, RA (May 1982). "Isolation of a transforming ... A proto-oncogene is a normal gene that could become an oncogene due to mutations or increased expression. Proto-oncogenes code ...
AMP-activated protein kinase (AMPK) RAF proto-oncogene serine/threonine-protein kinase (C-Raf) mammalian Target of Rapamycin ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". The ... Tuberous sclerosis is an autosomal dominant disease in which the genes required to express the tumor-suppressant proteins that ... Aspuria PJ, Tamanoi F (Oct 2004). "The Rheb family of GTP-binding proteins". Cellular Signalling. 16 (10): 1105-12. doi:10.1016 ...
... such mutated genes may act as oncogenes. Histidine-specific protein kinases are structurally distinct from other protein ... As shown in the adjacent picture, cooperative integrin-RTK signaling determines the timing of cellular survival, apoptosis, ... In this case, the G proteins are members of the Ras, Rho, and Raf families, referred to collectively as small G proteins. They ... This pathway is very complex and includes many protein components. In many cell types, activation of this pathway promotes cell ...
The Kit proto-oncogene encodes a tyrosine kinase receptor whose ligand is a paracrine protein called stem cell factor (SCF), ... The STAT proteins dimerize and enter the nucleus to act as transcription factors to alter gene expression. In particular, the ... Kolch, Walter (2000). "Meaningful relationships: The regulation of the Ras/Raf/MEK/ERK pathway by protein interactions". The ... Some of the proteins of the BMP family are BMP4 and BMP7. BMP4 promotes bone formation, causes cell death, or signals the ...
The AML1-ETO is incapable of p14ARF transcription as the fusion protein took on AML1's involvement with ARF gene expression and ... Mdm2 is a proto-oncogene that directly antagonizes p53 to ubiquitination (Figure 1). The p53 protein is known as the "guardian ... "Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR". BMC Cancer. 13 (1 ... Yu X, Ruan X, Zhang J, Zhao Q (2016). "Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT ...
The goal of oncogenomics is to identify new oncogenes or tumor suppressor genes that may provide new insights into cancer ... "SWI/SNF factors required for cellular resistance to DNA damage include ARID1A and ARID1B and show interdependent protein ... BRAF encodes a serine/threonine kinase that is involved in the RAS-RAF-MAPK growth signaling pathway. Mutations in BRAF cause ... They did have potential functions in metabolic pathways that suggested mechanisms by which they could act to promote cancer ( ...
B-Raf proto-oncogene, casein kinase 2-interacting protein 1, and filamin A. Functions of PAK1 are regulated by its ability to ... PAK1 regulates cytoskeleton remodeling, phenotypic signaling and gene expression, and affects a wide variety of cellular ... "p21-activated kinase 1 phosphorylates the death agonist bad and protects cells from apoptosis". Molecular and Cellular Biology ... Rettig M, Trinidad K, Pezeshkpour G, Frost P, Sharma S, Moatamed F, Tamanoi F, Mortazavi F (2012). "PAK1 kinase promotes cell ...
... and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by ... as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, ABL). The UPS is also involved in the regulation of ... The gene PSMA7 encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. This gene has 7 exons and ... as a negative regulator and may promote tumor growth by its inhibitory role on NOD1. PSMA7 has been shown to interact with ...
... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". The ... where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. The pro- ... Bcl-2 (B-cell lymphoma 2), encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins ... Wang HG, Rapp UR, Reed JC (November 1996). "Bcl-2 targets the protein kinase Raf-1 to mitochondria". Cell. 87 (4): 629-38. doi: ...
"SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and ... as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, ABL). The UPS is also involved in the regulation of ... and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by ... "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein". Nature. 418 (6898): 646-50 ...
Indeed, TBX3 can bypass cellular senescence, apoptosis and anoikis as well as promote uncontrolled cell proliferation, tumor ... The human TBX3 gene maps to chromosome 12 at position 12q23-24.1 and consists of 7 exons which encodes a 723 amino acid protein ... May 2013). "Oncogenic B-RAF(V600E) signaling induces the T-Box3 transcriptional repressor to repress E-cadherin and enhance ... May 2018). "KIP2 repression". Oncogene. 37 (21): 2773-2792. doi:10.1038/s41388-017-0090-2. PMID 29511350. S2CID 3706091. ...
The molecular weight of the according protein was published as 49 kDa. Three years later, the same gene was identified in ... "Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells". Oncogene. 24 ... In Schizosaccharomyces pombe, the CK1δ/ε orthologue Hhp2 promotes the cleavage of cohesion protein Rec8 possibly after its ... Good MC, Zalatan JG, Lim WA (May 2011). "Scaffold proteins: hubs for controlling the flow of cellular information". Science. ...
... normal genes involved in cell growth and proliferation or inhibition of apoptosis. If normal genes promoting cellular growth, ... Downstream effectors of Ras include three mitogen-activated protein kinases Raf a MAP Kinase Kinase Kinase (MAPKKK), MEK a MAP ... Proto-oncogeneEdit. A proto-oncogene is a normal gene that could become an oncogene due to mutations or increased expression. ... gene. When these two chromosome fragments fuse the genes also fuse creating a new gene: "BCR-ABL". This fused gene encodes for ...
Chen J, Fujii K, Zhang L, Roberts T, Fu H (July 2001). "Raf-1 promotes cell survival by antagonizing apoptosis signal- ... MAP3K5 gene coding for the protein is located on chromosome 6 at locus 6q22.33. and the transcribed protein contains 1,374 ... "Heat shock protein hsp72 is a negative regulator of apoptosis signal-regulating kinase 1". Molecular and Cellular Biology. 22 ( ... Oncogene. 18 (42): 5814-20. doi:10.1038/sj.onc.1202975. PMID 10523862. Human MAP3K5 genome location and MAP3K5 gene details ...
regulation of protein catabolic process. • cellular response to antibiotic. • negative regulation of gene expression. • ... The murine double minute (mdm2) oncogene, which codes for the Mdm2 protein, was originally cloned, along with two other genes ( ... "MDM2 suppresses p73 function without promoting p73 degradation". Molecular and Cellular Biology. 19 (5): 3257-66. doi:10.1128/ ... Podoptosis is caspase-independent and, therefore, different from apoptosis. The mitogenic role of MDM2 is also needed for wound ...
Gene ontology. Molecular function. • transferase activity. • nucleotide binding. • calcium ion binding. • protein kinase ... plasma membrane protein complex. • cytoplasm. Biological process. • cellular response to retinoic acid. • ureteric bud ... Crowder RJ, Enomoto H, Yang M, Johnson EM, Milbrandt J (October 2004). "Dok-6, a Novel p62 Dok family member, promotes Ret- ... The natural alternative splicing of the RET gene results in the production of 3 different isoforms of the protein RET. RET51, ...
This recruits the GEF called Sos, which activates the Ras G protein. Ras activates Raf (MAPKKK), which activates Mek (MAPKK), ... Deletion of the TOR1 gene in yeast increases cellular respiration in the mitochondria by enhancing the translation of ... Saucedo LJ, Gao X, Chiarelli DA, Li L, Pan D, Edgar BA (Jun 2003). "Rheb promotes cell growth as a component of the insulin/TOR ... Beauchamp EM, Platanias LC (Aug 2013). "The evolution of the TOR pathway and its role in cancer". Oncogene. 32 (34): 3923-32. ...
... cloning and characterization of a cellular p53 binding protein that interacts with Rb". Oncogene. 14 (2): 145-55. doi:10.1038/ ... Abl gene[31][32]. *Androgen receptor[33][34]. *Apoptosis-antagonizing transcription factor[35][36] ... protein to the chromatin, reducing transcription of S phase promoting factors, further suppressing DNA synthesis. ... "Raf-1 Physically Interacts with Rb and Regulates Its Function: a Link between Mitogenic Signaling and Cell Cycle Regulation" ...
... is an enzyme that in humans is encoded by the MAP2K7 gene. This protein is a member of the mitogen-activated protein kinase ... as well as pathological processes such as apoptosis and tumorigenesis. MKK7 are activated as a result of cellular stresses. ... MKK7 has also been suggested to function as a putative Metastase Suppressor Gene (MSG) by possibly promoting tumor dormancy at ... Karandikar M, Xu S, Cobb MH (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". The Journal of Biological ...
... proto-oncogene proteins c-jun - proto-oncogene proteins c-mo - proto-oncogene proteins c-myc - proto-oncogene proteins c-raf - ... fos gene - free energy - freezing point - FSH receptor - functional group - fungal protein - fungi - fusion oncogene protein - ... It deals with the structure and function of cellular components such as proteins, carbohydrates, lipids, nucleic acids and ... maturation-promoting factor - mechanoreceptor - Medicine - meiosis - Melting point - membrane glycoprotein - Membrane protein ...
positive regulation of gene expression. • protein-DNA complex disassembly. • ERK1 and ERK2 cascade. • cellular response to ... cellular proliferation and apoptosis". Oncogene. 22 (36): 5707-11. PMID 12944920. doi:10.1038/sj.onc.1206800.. ... "Interaction with WDR5 promotes target gene recognition and tumorigenesis by MYC". Molecular Cell. 58 (3): 440-52. PMC 4427524 ... Myc (c-Myc) is a regulator gene that codes for a transcription factor. The protein encoded by this gene is a multifunctional, ...
PTEN (phosphatase and tensin homolog) is a tumor suppressor gene encoding a protein PTEN, which possesses lipid and protein ... "Entrez Gene: MET met proto-oncogene (hepatocyte growth factor receptor)". Dean M, Park M, Le Beau MM, Robins TS, Diaz MO, ... and malignant transformation of the heart in the absence of the von Hippel-Lindau protein". Molecular and Cellular Biology. 28 ... In the injured heart, HGF/MET axis plays important roles in cardioprotection by promoting pro-survival (anti-apoptotic and anti ...
Cellular apoptosis susceptibility protein. *E2F. *Maturation promoting factor. *Wee. *Cullin (CUL7). Phases and. checkpoints. ... Neoplasm: Tumor suppressor genes/proteins and Oncogenes/Proto-oncogenes. Ligand. Growth factors. ... Gene ontology. Molecular function. • metal ion binding. • protein binding. • cyclin-dependent protein serine/threonine kinase ... protein kinase inhibitor activity. • protein kinase binding. • macromolecular complex binding. Cellular component. • cytoplasm ...
Hsp90 client proteins, activates the apoptosis-associated doublestranded RNA-dependent protein kinase, PKR and promotes an ... Gene expression profiling of human colon cancer cell lines with 17AAG proves that Hsp90 client protein genes are not affected ... Addition of such inhibitor causes proteosomal degradation of signaling proteins like steroid receptors, Raf kinase and Akt. ... Among heat shock proteins the focus on HSP90 has increased due to its involvement in several cellular phenomena and more ...
14-3-3 protein zeta/delta (14-3-3ζ) is a protein that in humans is encoded by the YWHAZ gene on chromosome 8. The protein ... including Raf kinases, BAX, BAD, NOXA, and caspase-2. For the most part,14-3-3ζ negatively regulates apoptosis by binding and ... "Mitotic phosphorylation of chromosomal protein HMGN1 inhibits nuclear import and promotes interaction with 14.3.3 proteins". ... For instance, 14-3-3ζ controls cellular senescence by complexing with BIS to chaperone protein folding of STAT3 and activate ...
Specifically, it has been found that a large percentage of melanomas have mutations in the B-RAF gene which leads to melanoma ... NUDT2 itself has also been shown to be associated with human breast carcinoma, where it promotes cellular proliferation. The ... also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene. ... Garraway LA, Sellers WR (August 2006). "Lineage dependency and lineage-survival oncogenes in human cancer". Nature Reviews. ...
... and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by ... as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of ... Apoptosis is mediated through disrupting the regulated degradation of pro-growth cell cycle proteins.[88] However, some cell ... The proteasomal degradation pathway is essential for many cellular processes, including the cell cycle, the regulation of gene ...
SH3 domain-mediated protein-protein interaction blocking drug". Oncogene. 21 (13): 2037-50. doi:10.1038/sj.onc.1205271. PMID ... identical protein binding. Cellular component. • cell-cell adherens junction. • apical junction complex. • trans-Golgi network ... "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Current Biology. 13 (17): 1459- ... Schmeiser K, Grand RJ (April 1999). "The fate of E- and P-cadherin during the early stages of apoptosis". Cell Death and ...
Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and ... The microscopic cellular characteristics of the tumor are reported from the analysis of tissue taken from a biopsy or surgery. ... Srikumar Chakravarthi; Baba Krishnan; Malathy Madhavan (1999). "Apoptosis and expression of p53 in colorectal neoplasms". ... promoting programmed cell death, antiproliferative effects, and epigenetic modification of cancer cells.[147] ...
... also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene. ... it has been found that a large percentage of melanomas have mutations in the B-RAF gene which leads to melanoma by causing an ... Cellular component. • nucleoplasm. • cell nucleus. • macromolecular complex. Biological process. • regulation of RNA ... Garraway LA, Sellers WR (2006). "Lineage dependency and lineage-survival oncogenes in human cancer". Nat. Rev. Cancer. 6 (8): ...
Almost 70% of all human protein coding genes are expressed in melanoma. Most of these genes are also expressed in other normal ... About 60% of melanomas contain a mutation in the B-Raf gene. Early clinical trials suggested that B-Raf inhibitors including ... Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin-dependent kinase that promotes cell ... a transcription factor involved in apoptosis and in fifty percent of human cancers. ...
The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf.[7] Raf in turn activates ... NF-κB regulates nuclear gene transcription to promote cell survival. Alternatively, programmed cell death occurs when TRAF6 and ... Cellular component. • endosome. • Golgi lumen. • extracellular region. • GO:0016023 cytoplasmic vesicle. • extracellular space ... It has been shown that the withdrawal of NGF induces apoptosis in pancreatic beta cells, signifying that NGF may play a ...
November 1999). "Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis ... Overexpression is induced as a result of gene amplification, growth factor or oncogene induced expression by Src, Ras, ErbB2, ... resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the ... Growth factors stimulate the Ras/Raf/ERK that induce cyclin D production. One of the members of the pathways, MAPK activates a ...
Many other cellular processes are influenced by O-GlcNAc such as apoptosis, the cell cycle, and stress responses. As UDP-GlcNAc ... Chen, Q; Chen, Y; Bian, C; Fujiki, R; Yu, X (2013-01-24). "TET2 Promotes Histone O-GlcNAcylation During Gene Transcription". ... regulating protein-protein interactions, altering protein structure or enzyme activity, changing protein subcellular ... S, Pathak; J, Alonso; M, Schimpl; K, Rafie; De, Blair; Vs, Borodkin; O, Albarbarawi; Dmf, van Aalten (Sep 2015). "The Active ...
CRK oncogene-like protein/focal adhesion kinase, the RAS/RAF/MEK/ERK pathway, c-Jun NH2-terminal kinase/stress-activated ... transduction pathways that promote proliferation and genetic instability while suppressing apoptosis and weakening cellular ... is the replacement of the first exon of c-Abl with sequences from the Bcr gene resulting in a Bcr-Abl fusion gene whose protein ... Inhibition of protein synthesis alters protein degradation through activation of protein kinase B (AKT). J Biol Chem. 2013; 288 ...
Cell signaling governs basic cellular activities and coordinates cell actions. Cell signaling may help diseases to be treated ... Notch proteins mediate critically important cellular functions through direct cell-cell contact. Notch signaling involves gene ... Activation of the tyrosine kinase promotes cell proliferation and suppresses apoptosis. HER2 can dimerize with any other member ... Ras-Raf-MEK-ERK Pathway Overview. The Ras-Raf-MEK-ERK Pathway is a critical cell signaling pathway with numerous implications ...
An important tumor suppressor gene is the gene encoding the cellular protein, p53, which is a 53 kD nuclear phosphoprotein that ... A number of oncogenes and oncogene families, including ras, myc, neu, raf, erb, src, fins, jun and abl, have now been ... it is thought that growth-promoting proto-oncogenes are counterbalanced by growth-constraining tumor suppressor genes. Several ... 2-methoxyestradiol-induced apoptosis in cancer cells WO1998007861A1 (en) * 1996-08-23. 1998-02-26. Board Of Regents, The ...
Human C-Raf Proto Oncogene Serine/Threonine Protein Kinase ELISA Kit-BAB83675.1 (MBS077112) product datasheet at MyBioSource, ... Protein kinase, Ser/Thr (non-receptor); Protein kinase, TKL; EC 2.7.11.1; Kinase, protein; TKL group; RAF family. Cellular ... apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade ... Product Gene Name CRAF elisa kit. [Similar Products] Research Use Only For Research Use Only. Not for use in diagnostic ...
Tai et al., "Axl promotes cell invasion by inducing MMP-9 activity through activation of NF-kappaB and Brg-1," Oncogene, Jul. ... Lai and Lemke, "An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system ... Linger et al., "Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity ... inhibitors of the Raf-MAPK pathway, inhibitors of JAK-STAT pathway, inhibitors of Pim kinases, and inhibitors of protein ...
A specific point mutation in codon 12 converts the H-Ras gene into an active oncogene. Ras gene mutations (H-Ras and N-Ras) ... Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK/activator protein-1 (AP-1) ... dRzIKK induction of cellular apoptosis. A, paraffin-embedded liver tissues with micrometastatic Ras-melanoma were subjected to ... Given the important role that NF-κB plays in promoting melanoma tumor growth, it is not surprising that NF-κB activation is a ...
Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1.; Science, 2004 PubMed Europe PMC* ... Genes Dev, 2000 PubMed Europe PMC*Suzuki K, Kodama S, Watanabe M; Recruitment of ATM protein to double strand DNA irradiated ... RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins.; Cell, 2007 PubMed Europe ... Apoptosis. TP53BP1. RAD51. UPF1. CASP9. CHK1. NBN. RAD50. MDC1. RAD52. BLM. mRNA nonsense-mediated. decay (NMD). CHK2. TP53. ...
Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkins lymphoma. Science 1994;263:1281-1284. ... It was originally identified as the cellular homolog of the product of the v-Myc oncogene of the avian myelocytomatosis virus. ... protein phosphatases, transcription factors, apoptosis and cell-cycle regulators, adaptor proteins, and other molecules has ... Akt resides in its ability to sequester the proapoptotic protein Bad and promote its binding to the cytoplasmic 14-3-3 proteins ...
Protein Coding), Raf-1 Proto-Oncogene, Serine/Threonine Kinase, including: function, proteins, disorders, pathways, orthologs, ... Entrez Gene Summary for RAF1 Gene. * This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP ... Apoptosis and survival_Anti-apoptotic action of nuclear ESR1 and ESR2. *Apoptosis and survival_Regulation of Apoptosis by ... displaces 14-3-3 proteins from RAF1 and activates RAF1 (PubMed:22886302). Interacts with PDE8A; the interaction promotes RAF1 ...
We tested this hypothesis and evalu- many genes that are involved in a variety of cellular ated the role of gastrin in GC ... docetaxel-induced apoptosis of androgen-independent human prostate 59. Yang M, Huang CZ. Mitogen-activated protein kinase ... v-Raf murine sarcoma viral oncogene homolog B; CAG: Chronic atrophic gastritis; CCK-8: Cell Counting comparison with treatment ... ated with GC pathogenesis by promoting sequestration 24 axis. of P16 in the cytoplasm and promoting alkalization of In a recent ...
SR proteins: a conserved family of pre-mRNA splicing factors. Genes Dev 1992; 6: 837-47. ... resulting in activation of the proto-oncogenes Ras and Raf. Signals through this hierarchical kinase pathway culminate in the ... the precise cellular localization of this protein within breast and colon has not been described. Immunohistochemical analysis ... Only Akt1 is required for proliferation, while Akt2 Promotes cell cycle exit through p21 binding. Mol Cell Biol 2006; 22: 8267- ...
Similarly, persistent activation of Ras and Raf proteins that activate ERK is sufficient to promote EMT and contributes to ... gene repression is an important part of the cellular response to TGF-β, as it affected one-third of TGF-β target genes (Fig. 2d ... invasiveness and metastasis formation in carcinomas with activated ras oncogenes (22). However, the underlying genetic programs ... and induces apoptosis via activation of caspases (10). ... Induced genes are colored in red, repressed genes in green. ...
Select your gene target of interest using an interactive pathway map, and select your plate. ... scaffold coordinating the Raf (v-myc myelocytomatosis viral oncogene homolog (c-Raf-1))/ Mitogen-activated protein kinase ... Ceramides then promotes Ras-dependent apoptosis [21]. PKC-zeta directly binds and activates Mitogen-activated protein kinase ... Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Leukemia : official journal of the Leukemia ...
ATG genes) suppresses the transforming ability of Ras, thus suggesting that activated oncogenes require autophagy to promote ... Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J. Cell Mol. Med. 2010, 14, ... Resulting cellular adjustments and modifications modulate vascular supply and immune cell migration and mediate the release of ... when stimulated by the RAS-RAF-MEK pathway [72]. It is thus clear that a complex network of molecular events is involved in the ...
Genomes and Genes, Publications, Research Topics, Scientific Experts, Species, Locale about phosphatidylethanolamine binding ... proto oncogene proteins c raf*mads domain proteins*yy1 transcription factor*proto oncogene proteins b raf*hmga2 protein*i kappa ... Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells. .. ... Genomes and Genes. *PEBP1 products*Pebp1 products*Pebp1 products*PEBP4 products*Raf-1 products*TSF *B-Raf products*FT products* ...
"Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene." Cell Death and Differentiation In: , Vol. 12, No ... "N terminus of ASPP2 binds to Ras and enhances Ras/Raf/MEK/ERK activation to promote oncogene-induced senescence." Proceedings ... "Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response ... "Proapoptotic p53-interacting protein 53BP2 is induced by UV irradiation but suppressed by p53." Molecular and Cellular Biology ...
Examples of well validated 14-3-3 interaction partners are the proto-oncogene RAF-1 (7-9) and the cell-cycle regulatory ... elegans when promoted by extra copies of the sir-2.1 gene (33). ... activation of JNK1 and p38 MAPK leading to increased apoptosis ... monomeric and dimeric states and suggests that these 14-3-3 proteins may use the dimerization process to control their cellular ... Structural basis for protein-protein interactions in the 14-3-3 protein family. Xiaowen Yang, Wen Hwa Lee, Frank Sobott, ...
In this study the effect of the Raf kinase inhibitor BAY 43-9006 and of the MEK inhibitor CI-1040 (PD184352) on a Raf dependent ... In contrast, the Raf inhibitor BAY 43-9006 did not influence adenoma formation in vivo. The MEK inhibitor CI-1040 may be used ... For example, Ras and Raf kinase inhibitors are already in a number of ongoing phase II and phase III clinical trials. ... We have generated a lung cancer mouse model by targeting constitutively active C-Raf kinase to the lung. These mice develop ...
Interestingly, PLX4032 promotes the phosphorylation of these signaling molecules in BRAF-wild-type thyroid cells. These ... In addition, expression of proteins within the MAPK signal transduction pathway was analyzed by Western blot. PLX4032 has ... Our laboratory evaluated cellular phenotypic effects in response to treatment with PLX4032, a BRAFV600E-specific inhibitor, in ... Garnett MJ, Marais R: Guilty as charged: B-RAF is a human oncogene. Cancer cell. 2004, 6 (4): 313-319. 10.1016/j.ccr.2004.09. ...
Notably, combination treatment promoted greater cellular loss of these proteins, suggesting that mTOR signaling represents a ... c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma. Cancer Cell 2011;19: ... Notably, YB-1 has been identified as an essential regulator of proliferation and gene expression in KRAS oncogene-transformed ... promoting apoptosis, as has been reported in breast carcinoma (45). Studies confirming the role of YB-1 in the enhanced ...
... which regulates the levels of pro-apoptotic protein BAK1 and inhibitors of apoptosis (IAPs), and the RAS-RAF pathway, which ... In this Review, we describe how RAS oncogenes exploit their extensive signalling reach to affect multiple cellular processes ... Once released, E2F transcription factors transactivate several genes that are required for cell cycle progression, including ... Oncogenic RAS establishes independence from extracellular growth factors and growth inhibitors, thereby promoting exit from the ...
1996) Protein kinase C ζ reverts v‐raf transformation of NIH‐3T3 cells. Genes Dev, 10, 1455-1466. ... a gene induced during apoptosis, interacts selectively with the atypical isoforms of protein kinase C. Cell, 86, 777-786. ... Gaynor R (1992) Cellular transcription factors involved in the regulation of HIV‐1 gene expression. AIDS, 6, 347-363. ... raf oncogene (Kieser et al., 1996). Lastly, overexpression of PKC ζ in prostate cancer cells inhibited metastasis (Powell et al ...
The B-raf/c-Rmil proto-oncogene belongs to the raf/mil family of serine/threonine protein kinases. It encodes multiple protein ... By gene array analysis, FOXO3a was found to modulate the expression of several genes that regulate the cellular response to ... Activated CREB promoted cell survival, and inhibition of CREB phosphorylation at serine 133 triggered apoptosis. These findings ... B-RAF PROTEIN ISOFORMS INTERACT WITH AND PHOSPHORYLATE MEK-1 ON SERINE RESIDUE-218 AND RESIDUE-222 ONCOGENE Papin, C., Eychene ...
HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the ... We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, ... gene is a regulator of apoptosis induced by ultraviolet light and cisplatin. Oncogene. 2004, 23 (1): 201-212. 10.1038/sj.onc. ... the activation of Ras/Raf/mitogen-activated protein (MAP) kinase, MEKK1/Jun kinase, [13] protein kinase C signal transduction ...
... thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on Tyr-284 and ... apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification ... receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling ... Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor ( ...
Oncogenic B-RAF negatively regulates the tumor suppressor LKB1 to promote melanoma cell proliferation. Mol Cell 2009;2:237-47. ... AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007;10:774-85. ... PPARγ controls cell proliferation and apoptosis in an RB-dependent manner. Oncogene 2003;27:4186-93. ... of the endogenous 18S reference gene to the target gene (ΔCt = Ct of target gene − Ct of 18S). Values are expressed as the ...
Imada K et al. Mutual regulation between Raf/MEK/ERK signaling and Y-box-binding protein-1 promotes prostate cancer progression ... Cellular and biochemical assays. By product type. Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists ... Zheng X et al. The coiled-coil domain of oncogene RASSF 7 inhibits hippo signaling and promotes non-small cell lung cancer. ... Leeb M & Wutz A Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in ...
Down-regulating ENTPD7 could inhibit lung cancer cell proliferation and promote apoptosis via inhibiting the Ras/Raf/MEK/ERK ... Silencing ENTPD7 also inhibited the expression levels of Ras and Raf proteins and the phosphorylation of mitogen-activated ... Plasmid transfection technology was also applied to silence ENTPD7 gene. Crystal violet staining and flow cytometry were ... Down-regulation of the expression of ENTPD7 inhibited proliferation but promoted apoptosis of lung cancer cell. ...
... genes involved in nucleotide and nucleic acid metabolism, and genes involved in protein metabolism (Fig. 8). Because MycN ... Schwab M. Human neuroblastoma: from basic science to clinical debut of cellular oncogenes. Naturwissenschaften 1999;86:71-8. ... Raf-1 kinase assay. We determined Raf-kinase activity using a Raf-1 immunoprecipitation kinase cascade assay kit (Upstate ... The Myc proteins are short-lived nuclear transcription factors that regulate cell growth and apoptosis (1). Defects in the Myc ...
wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary ... E2F1 regulates the base excision repair gene XRCC1 and promotes DNA repair. Chen, D., Yu, Z., Zhu, Z., Lopez, C.D. J. Biol. ... Oncogene-specific gene expression signatures at preneoplastic stage in mice define distinct mechanisms of hepatocarcinogenesis. ... Adenovirus-mediated E2F-1 gene transfer sensitizes melanoma cells to apoptosis induced by topoisomerase II inhibitors. Dong, Y. ...
  • RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). (genecards.org)
  • Here we report a transcriptome screen of genetic programs of TGF-β-induced EMT in human keratinocytes and propose functional roles for extracellular response kinase (ERK) mitogen-activated protein kinase signaling in cell motility and disruption of adherens junctions. (pnas.org)
  • Recent reports have described multifaceted interactions between the mitogen-activated protein kinase (MAPK) and AKT signaling networks and the splice regulatory machinery. (aacrjournals.org)
  • Ceramide produced by Neutral sphingomyelinase stimulates Ceramides -activated Mitogen-activated protein kinase 1 and 3 ( ERK1/2 ) cascade and Acid sphingomyelinase may couple the TNF-R1 to the secretary pathway and to apoptosis via Cathepsin D [ 6 ]. (bio-rad.com)
  • Silencing ENTPD7 also inhibited the expression levels of Ras and Raf proteins and the phosphorylation of mitogen-activated protein kinase (MEK) and extracellular signal-regulated kinase (ERK). (biomedcentral.com)
  • RAF proteins are part of the conserved MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) signaling cascade between the cell surface and the nucleus. (atlasgeneticsoncology.org)
  • BCR-ABL activates several pathways such as RAS, a small GTPase, mitogen activated protein kinase (MAPK), signal transducers and activator of transcription (STAT), and phosphoinositide 3-kinase (PI3K) pathways that regulate survival, proliferation, and apoptosis of leukemic cells [ 8 - 16 ] (Figure 1 ). (hindawi.com)
  • Deregulation of phosphatidylinositol 3-kinase/Akt and Ras/Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase pathways occurs in melanoma and breast cancer, deregulating normal cellular apoptosis and proliferation. (aacrjournals.org)
  • Sorafenib and nanoliposomal ceramide synergistically inhibited cultured cells by cooperatively targeting mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling. (aacrjournals.org)
  • Both melanoma and breast cancer have deregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt and Ras/Raf/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK pathways, which regulate apoptosis and cellular proliferation, respectively ( 2 , 3 ). (aacrjournals.org)
  • Despite this hyperactivation, which has also been confirmed by others, Vemurafenib still strongly limited IAV-induced activation of other signaling cascades especially of p38 and JNK mitogen-activated protein kinase (MAPK) pathways. (frontiersin.org)
  • Now we know that c-Raf is a principal component of the first described mitogen-activated protein kinase (MAPK) pathway: ERK1/2 signaling. (wikipedia.org)
  • The disease is driven by molecular alterations in oncogenic signaling pathways, such as mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3K). (intechopen.com)
  • In this review, we will focus on the mitogen-activated protein kinase (MAPK) cascades downstream of the epidermal growth factor receptor (EGFR), Notch, PI3K/AKT pathway, transforming growth factor-β (TGF-β), and Wnt signaling pathways. (springer.com)
  • p90 ribosomal S6 kinase (RSK), a serine threonine kinase that lies downstream of the Ras-MAPK (mitogen activated protein kinase) cascade, has been demonstrated to be involved in the regulation of cell proliferation in various malignancies through indirect (e.g., modulation of transcription factors) or direct effects on the cell-cycle machinery. (biomedcentral.com)
  • Both ATM and DNA-PK promote sequential activation of the mitogen-activated protein kinase (MAPK)/p90 rsk signaling cascade in a p53-independent fashion. (asm.org)
  • To this end, combined treatment with B-RAF and mitogen activated protein kinase kinase (MEK) inhibitors has been proposed, although resistance still develops in most patients, by not yet fully elucidated mechanisms, after an average of 9.4 months [ 8 ]. (hindawi.com)
  • For instance, point mutation of serine-threonine protein kinase B-RAF ( BRAF ) occurs in approximately one-third to one-half of PTC cases, and BRAF can result in the activation of the carcinogenic mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase signaling pathway ( 4 ). (spandidos-publications.com)
  • Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. (mdpi.com)
  • PI-3 kinase: phosphoinositol-3 kinase, RIP: receptor interactive protein, SOD: superoxide dismutase, MTP: mitochondrial transition pore, Apaf-1: apoptotic protease activation factor, MHC: major histocompatibility complex, TGF-α: transforming growth factor α, ROS: reactive oxygen species, MAPK: mitogen-activated protein kinase, NSAID: non-steroidal anti-inflammatory drug. (isciii.es)
  • The RAS-RAF-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway provides numerous opportunities for targeted oncology therapeutics. (proteopedia.org)
  • Activation of the tyrosine kinase promotes cell proliferation and suppresses apoptosis. (rockland-inc.com)
  • Accumulating evidence indicates that NF-κB, as a central regulator of gene expression, plays a crucial role in controlling cell proliferation, apoptosis, and tumorigenesis ( 3 - 6 ). (aacrjournals.org)
  • Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. (genecards.org)
  • Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). (genecards.org)
  • Signaling networks promoting cell growth and proliferation are frequently deregulated in cancer. (biomedcentral.com)
  • Both kinases are essential for cellular homeostasis and induce both proliferation and survival by suppression of apoptosis [ 5 ]. (biomedcentral.com)
  • Most of the thyroid cancers are believed to originate in single cells due to mutations that confer growth advantages including increased proliferation, impaired apoptosis, enhanced angiogenesis, invasion and metastasis. (biomedcentral.com)
  • KRAS is a member of the RAS family of oncogenes, a collection of small guanosine triphosphate (GTP)-binding proteins that integrate extracellular cues and activate intracellular signaling pathways to regulate cell proliferation, differentiation, and survival ( 9 ). (aacrjournals.org)
  • Here, we show that SV40 small t can substitute for tumor necrosis factor‐α (TNF‐α) or serum and stimulate atypical protein kinase C ζ (PKC ζ) activity, resulting in MEK activation, cell proliferation and NF‐κB‐dependent gene transcriptional activation in CV‐1 and NIH 3T3 cells. (embopress.org)
  • an inducible transcriptional activator that participates in the control of cell proliferation and survival, as well as in inflammatory response and viral gene expression (reviewed in Bauerle and Baltimore, 1996 ). (embopress.org)
  • In the mature prostatic gland, the androgen receptor regulates the expression of genes involved in diverse cellular functions, including survival and proliferation of the epithelial cells and lipid metabolism ( 1 ). (aacrjournals.org)
  • Moreover, studies with chemical inhibitors have revealed that inhibition of FAS activity results in decreased proliferation and increased apoptosis of cancer cells ( 11 ). (aacrjournals.org)
  • Crystal violet staining and flow cytometry were performed to determine cell proliferation and apoptosis. (biomedcentral.com)
  • Down-regulation of the expression of ENTPD7 inhibited proliferation but promoted apoptosis of lung cancer cell. (biomedcentral.com)
  • Down-regulating ENTPD7 could inhibit lung cancer cell proliferation and promote apoptosis via inhibiting the Ras/Raf/MEK/ERK pathway. (biomedcentral.com)
  • Therefore, this study mainly explored the expression characteristics of ENTPD7 in lung cancer, the effects of ENTPD7 on the proliferation and apoptosis of lung cancer cells and the mechanism of action. (biomedcentral.com)
  • The active GTP-bound Ras in turn activates a multitude of downstream effectors, including Raf-1, phosphoinositide 3-kinase (PI3K), and Ral-guanine-nucleotide exchange factors, which regulate cell proliferation, differentiation, survival, and death ( 3 ). (aacrjournals.org)
  • Rates of proliferation, apoptosis, and angiogenesis were measured in size- and time-matched tumors to identify mechanistic basis for inhibition. (aacrjournals.org)
  • A 1- to 2-fold increase in cellular apoptosis and 3- to 4-fold decrease in cellular proliferation were observed following combination treatment compared with single agents, which caused synergistically acting inhibition. (aacrjournals.org)
  • Thus, a cocktail of agents targeting these pathways could have significant therapeutic potential by simultaneously increasing cellular apoptosis and/or decreasing proliferation in a cooperative manner. (aacrjournals.org)
  • ROS have been implicated in the regulation of diverse cellular functions including defense against pathogens, intracellular signaling, transcriptional activation, proliferation, and apoptosis. (aspetjournals.org)
  • At the cellular level, concomitant up-regulation of AKT and N-Ras resulted in increased proliferation and microvascularization when compared with AKT-injected mice. (nih.gov)
  • Our research program focuses on the mechanisms that control the proliferation of mammalian cells under normal and pathological conditions (regeneration, cancer), with a particular emphasis on stem cells and gene regulatory networks. (stanford.edu)
  • Cancer cell proliferation, apoptosis, angiogenesis, invasion, and metastasis are regulated by an interconnecting network of cellular signaling pathways involving extracellular ligands, transmembrane receptors, intracellular signaling protein kinases, and transcription factors. (ahajournals.org)
  • The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that responds to a wide range of chemicals, including chemical carcinogens such as dioxins and carcinogenic polyaromatic hydrocarbons, and induces a battery of genes associated with detoxification, proliferation, and immune regulation. (frontiersin.org)
  • Activating oncogenic mutations in BRAF and NRAS have been identified in 40-60% and 15-20% of melanoma patients, respectively, leading to constitutive pathway signaling that promotes cell proliferation and survival [ 6 , 7 ]. (intechopen.com)
  • Hepatitis B and C viruses seem to be involved in neoplastic transformation through both direct and indirect mechanisms, due to inflammation process and the capacity of viral proteins in modulating the proliferation and the death of infected hepatocytes. (unipd.it)
  • This study aimed to analyze the crucial role that proteins of the Wnt signaling pathway play in stem cell proliferation. (spandidos-publications.com)
  • The EGFR signaling pathway participates in many cellular processes, including the growth, proliferation and survival of normal cells. (springer.com)
  • PI3K can prevent apoptosis and promote cellular survival and proliferation in a wide variety of cells. (spandidos-publications.com)
  • Akt is a serine/threonine-specific protein kinase, which plays a key role in apoptosis and cell proliferation. (spandidos-publications.com)
  • BCL-2 ), these proteins undergo a gain of function to promote hyper-proliferation or sustained survival despite pro-apoptotic signaling. (biomedcentral.com)
  • Likewise, tumor suppressor proteins (e.g., p53 and PTEN) negatively regulate survival and proliferation following cellular stress, but when mutated or deleted, they fail to appropriately restrain proliferation and this has potential to promote genomic instability and organelle dysfunction. (biomedcentral.com)
  • Activating mutations of the B-RAF oncogene are present in approximately 5-10% of all human malignancies and cause aberrant cell proliferation. (hindawi.com)
  • MicroRNAs (miRNA) are a recently discovered family of short non-protein-coding RNAs with diverse functions, including regulation of cellular differentiation, proliferation and apoptosis. (libpubmedia.co.uk)
  • Mammary glands from MMTV (mouse mammary tumor virus)- neu/p27 +/− mice exhibited alveolar hyperplasia, enhanced proliferation, decreased apoptosis, and accelerated tumor formation compared to MMTV - neu/p27 +/+ glands. (asm.org)
  • Mitogen-activated protein kinases (MAPKs) are important signaling molecules that influence a broad range of cellular processes such as proliferation, differentiation, migration and apoptosis. (mdpi.com)
  • In melanoma the proliferation signal goes mainly through MAPK signalling (Ras/Raf/MEK/ERK), which is activated in approximately 80-90% of melanoma cases. (termedia.pl)
  • The Drosophila sterile-20 kinase slik controls cell proliferation and apoptosis during imaginal disc development. (nih.gov)
  • Proliferative stimuli generally also induce apoptosis, and anti-apoptotic factors are required to allow net cell proliferation. (nih.gov)
  • Genetic studies in Drosophila have led to identification of a number of genes that control both processes, providing new insights into the mechanisms that coordinate cell growth, proliferation, and death during development and that fail to do so in diseases of cell proliferation. (nih.gov)
  • We present evidence that the Drosophila Sterile-20 kinase Slik promotes cell proliferation and controls cell survival. (nih.gov)
  • Like some oncogenes, excess Slik activity stimulates cell proliferation, but this is compensated for by increased cell death. (nih.gov)
  • We suggest that Slik mediates growth and survival cues to promote cell proliferation and control cell survival during Drosophila development. (nih.gov)
  • These observations suggested that slik, like many oncogenes, promotes cell proliferation and apoptosis in parallel. (nih.gov)
  • THE ras genes encode highly conserved GTP-binding proteins that regulate cell growth, proliferation, and differentiation in almost all multicellular eukaryotes (reviewed in M c C ormick 1994 ). (genetics.org)
  • Since the R7 cell is specified from a group of postmitotic cells, the role of Ras in this pathway may differ from pathways where Ras promotes growth and cell proliferation. (genetics.org)
  • We focus on how the retinoblastoma protein and its downstream target E2F transcription factor mediate proliferation, differentiation and apoptosis in response to specific signaling cascades. (moffitt.org)
  • Disruption of the Rb-Raf-1 interactions by a small peptide inhibits cell proliferation as well as VEGF-induced angiogenic process. (moffitt.org)
  • Efforts are being made to understand the specific mechanism by which prohibitin regulates cell proliferation and apoptosis. (moffitt.org)
  • On the other hand, gastric mucosal infection by Helicobacter pylori may affect the normal balance between gastric epithelial proliferation and death from apoptosis, thus disregulating the normal cell cycle and initially leading to gastritis. (isciii.es)
  • The Inhibitor of Apoptosis (IAP) proteins act downstream of a broad range of stimuli, such as cytokines and extracellular matrix interactions, to regulate cell survival, proliferation and migration. (omicsonline.org)
  • TGF-β regulates a plethora of cellular processes including cell proliferation, differentiation, migration, organization and death [ 1 ]. (biomedcentral.com)
  • Preclinical testing with Hsp90 inhibitors has demonstrated reduced proliferation, enhanced apoptosis and synergism with chemotherapies and radiation. (oncotarget.com)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • By studying the autophosphorylation behavior of this pathway, and the influence of STAT proteins in other pathways, researchers gain valuable insight into understanding how this essential signaling system interacts with cellular functions. (rockland-inc.com)
  • Increased understanding of the cell cycle pathways and genetic alterations involve in inhibitor A of cyclin-dependent kinase (CDK) 4/alternative reading frame ( INK4a/ARF ) gene. (aacrjournals.org)
  • The gene expression profiling approach delineates complex context-dependent signaling pathways and transcriptional events that determine epithelial cell plasticity controlled by TGF-β. (pnas.org)
  • Investigation of the identified pathways and genes will advance the understanding of molecular mechanisms that underlie tumor invasiveness and metastasis. (pnas.org)
  • Although both phosphatidylinositol-3 kinase and extracellular response kinase (ERK) mitogen-activated protein (MAP) kinase signaling pathways have been implicated in TGF-β-induced EMT ( 20 , 21 ), their specific roles and proximal target gene programs in EMT remain unclear. (pnas.org)
  • Although Smad proteins are considered important mediators ( 12 , 23 , 24 ), Smad-independent TGF-β signaling has been demonstrated, involving predominantly MAP kinase pathways. (pnas.org)
  • Ceramides regulate diverse signaling pathways involving apoptosis, cell senescence, the cell cycle, and differentiation. (bio-rad.com)
  • The seven members of the human 14-3-3 protein family regulate a diverse range of cell signaling pathways by formation of protein-protein complexes with signaling proteins that contain phosphorylated Ser/Thr residues within specific sequence motifs. (pnas.org)
  • RAS proteins are essential components of signalling pathways that emanate from cell surface receptors. (nih.gov)
  • A wealth of biochemical and genetic studies indicates that RAS proteins control a complex molecular circuitry that consists of a wide array of interconnecting pathways. (nih.gov)
  • These mechanisms include insertional mutagenesis upon integration, trans-activation of the cellular genes, activation of signaling pathways, inactivation of tumor suppressor proteins, synergy with environmental carcinogenesis and host immune response. (biomedcentral.com)
  • Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. (uniprot.org)
  • Inhibition of active Ras by farnesylthiosalicylic acid led to attenuation of the Raf-MEK-ERK and phosphoinositide 3-kinase-Akt-glycogen synthase-3 (GSK-3) pathways, to reduction in cyclin D1, phospho-retinoblastoma, and E2F, and to increase in the cyclin-dependent kinase inhibitor p27 and in retinoblastoma-binding protein-1, an inhibitor of E2F transcriptional activity. (aacrjournals.org)
  • The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions. (jci.org)
  • In addition, we consider cytokine-dependent pathways of apoptosis regulation (STAT-signaling pathway and tumor necrosis factor (TNF)-dependent pathway). (intechopen.com)
  • Therapeutic cocktails simultaneously targeting these pathways could promote synergistically acting tumor inhibition. (aacrjournals.org)
  • This has led to investigation of strategies simultaneously inhibiting the action of multiple targets or pathways to regulate processes promoting tumor development. (aacrjournals.org)
  • Dramatic elevation of ROS, exceeding compensatory changes in the level of the endogenous thiol buffers, may result in the sustained activation of signaling pathways and expression of genes that induce apoptosis in affected cells. (aspetjournals.org)
  • This manuscript summarizes recent research findings including studies of global gene expression in MEN1-associared neuroendocrine tumors and pivotal changes in intracellular signaling pathways associated with neuroendocrine tumorigenesis. (springer.com)
  • AKT (v-akt murine thymoma viral oncogene homolog 1) and N-Ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes rapid carcinogenesis by way of mTOR (mammalian target of rapamycin complex 1), FOXM1 (forkhead box M1)/SKP2, and c-Myc pathways. (nih.gov)
  • Activation of v-akt murine thymoma viral oncogene homolog (AKT) and Ras pathways is often implicated in carcinogenesis. (nih.gov)
  • Our data demonstrate the in vivo crosstalk between the AKT and Ras pathways in promoting liver tumor development, and the pivotal role of mTORC1-dependent and independent pathways in mediating AKT and Ras induced hepatocarcinogenesis. (nih.gov)
  • We combine genetic, genomics, and proteomics approaches to identify and investigate genes and pathways involved in cancer initiation and progression. (stanford.edu)
  • Ras proteins are involved in the transduction of signals elicited by activated surface receptors, acting as key components by relaying signals downstream through diverse pathways. (embl.de)
  • The biology of tumors is further modified by factors such as epigenetic regulators of chromatin structure, and pathways that regulate protein stability such as molecular chaperones and ubiquitin-proteasome pathways. (ahajournals.org)
  • Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored. (biomedcentral.com)
  • Activation of the Ras→Raf→MEK→ERK and JNK intracellular pathways down-regulated p8 expression. (biomedcentral.com)
  • p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. (biomedcentral.com)
  • Various genes, are associated to the signaling pathways, which have been frequently reported to be dysregulated due to mutations or the altered function of their products in the CRC. (springer.com)
  • Lee et al also showed that flavonoids isolated from Citrus platymamma induce mitochondrial-dependent apoptosis in AGS cells by modulation of the PI3K/AKT and MAPK pathways ( 17 ). (spandidos-publications.com)
  • However, in cancer biology, we are still gaining an understanding of all the signaling pathways that promote tumorigenesis and how these pathways can be pharmacologically manipulated by conventional and targeted therapies. (biomedcentral.com)
  • Within this review, we present the pathways that govern the cellular decision to undergo apoptosis as three distinct, yet connected puzzle pieces: (1) How do oncogene and tumor suppressor pathways regulate apoptosis upstream of mitochondria? (biomedcentral.com)
  • When these pieces are united, it is possible to appreciate how cancer signaling directly impacts upon the fundamental cellular mechanisms of apoptosis and potentially reveals novel pharmacological targets within these pathways that may enhance chemotherapeutic success. (biomedcentral.com)
  • In multi-cellular organisms, cell growth, cell division, and cell death are regulated by a host of signaling pathways that integrate cellular condition and context. (biomedcentral.com)
  • Despite the many signaling pathways that lead to cancer vulnerability, most would agree that the best method to treat cancer is to specifically eliminate diseased cells via a genetically controlled program of cell death termed apoptosis. (biomedcentral.com)
  • This observation implies that mutant B-RAF must combine with additional genetic aberrations and/or alterations of other signaling pathways to generate and sustain melanoma [ 1 , 6 ]. (hindawi.com)
  • In fact, despite the discovery of selective B-RAF inhibitors, their efficacy in melanoma, as single targeted therapy, was lower than hoped for because of the activation of alternative mitogen activated protein kinases (MAPK) pathways and consequent development of tumour resistance [ 7 ]. (hindawi.com)
  • There is evidence that different isoforms of PI3K's activate specific signaling pathways and are thus responsible for integrating cellular responses. (embl.de)
  • Activated Ras proteins bind to and activate several distinct downstream effector pathways, including Raf, Ral-GDS, and PI3-kinase. (genetics.org)
  • A malignant cell phenotype is initiated when mutant cholangiocytes produce mitogens that activate local cellular receptors and intracellular signaling pathways ( 4 , 6 ). (iiarjournals.org)
  • We focus on regulatory pathways that promote tumor growth, angiogenesis and metastasis and how they can be targeted for drug discovery. (moffitt.org)
  • Mutations of the prohibitin gene have been reported in breast cancer and we find that prohibitin can inhibit certain apoptotic pathways. (moffitt.org)
  • These genes were then placed in appropriate pathways in an attempt to understand the molecular basis of homocysteine induced complex disorders and to provide a resource for selection of genes for polymorphism screening and analysis of mutations as well as epigenetic modifications in relation to hyperhomocysteinemia. (biomedcentral.com)
  • Mapping the genes to their respective pathways revealed that an elevated level of homocysteine leads to the atherosclerosis either by directly affecting lipid metabolism and transport or via oxidative stress and/or Endoplasmic Reticulum (ER) stress. (biomedcentral.com)
  • Deregulated PI3 and mitogen activated protein (MAP) kinase pathways promote early melanocytic lesion development and confer drug resistance. (aacrjournals.org)
  • Development of melanomas from melanocytes is a multistage complex process involving changes in expression and activities of a number of genes and signaling pathways regulating cellular differentiation, growth, senescence, survival, and migration ( 8 ). (aacrjournals.org)
  • TGF-β and Ras signaling are two of the most important molecular pathways mediating the fundamental cellular process, namely EMT, involved in tumor metastasis [ 21 , 22 ]. (biomedcentral.com)
  • Learn about the cellular, molecular, and biochemical pathways of CRISPR-associated proteins, DNA repair pathways, and applications in diverse organisms, including for human health and disease biology. (nyas.org)
  • DSBs trigger a multitude of post-translational modifications that alter both, catalytic activities and the specificity of protein interactions including: phosphorylation, methylation, ubiquitylation, acetylation, and SUMOylation, followed by the turnaround of these changes as repair has been completed. (wikipathways.org)
  • Serine-arginine proteins comprise a family of splice factors that are activated after phosphorylation by SRPKs in the cytoplasm. (aacrjournals.org)
  • This prevents BCL2-associated agonist of cell death ( BAD ) phosphorylation and leads to apoptosis in COS-7 cells. (bio-rad.com)
  • Recently, a small number of proteins that interact with 14-3-3 proteins via a C-terminal phosphorylation motif have also been identified ( 20 , 21 ). (pnas.org)
  • Phosphorylation-dependent and -independent binding have been shown to be targeted to the same site of the 14-3-3 proteins ( 18 ). (pnas.org)
  • Interestingly, PLX4032 promotes the phosphorylation of these signaling molecules in BRAF-wild-type thyroid cells. (biomedcentral.com)
  • When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (By similarity). (uniprot.org)
  • Phosphorylation of Thr 58 is catalyzed by glycogen synthase-3 (GSK-3) and targets c-Myc to the ubiquitin-proteasome protein degradation pathway. (aacrjournals.org)
  • The RAF proteins exhibit complex regulation involving numerous phosphorylation sites throughout the proteins. (atlasgeneticsoncology.org)
  • RAF-1 is capable of activating the NF-kB transcription factor through an unknown mechanism that does not seem to involve direct phosphorylation of NF-kB and is independent of MEK1/2-ERK1/2 signaling. (atlasgeneticsoncology.org)
  • Synthesized peptide derived from human Raf-1 around the phosphorylation site of S259. (stjohnslabs.com)
  • The MAPK signaling cascade relays an ordered series of consecutive phosphorylation events from cell surface, via Ras, Raf, MEK, and ERK, to nucleus ( 4 , 5 ). (aacrjournals.org)
  • Rb is a multifunctional protein with many binding and phosphorylation sites. (wikipedia.org)
  • Within each domain, there are a variety of protein binding sites, as well as a total of 15 possible phosphorylation sites. (wikipedia.org)
  • Generally, phosphorylation causes interdomain locking, which changes Rb's conformation and prevents binding to target proteins. (wikipedia.org)
  • A membrane-based antibody array for the parallel determination of the relative levels of human protein kinase phosphorylation. (rndsystems.com)
  • Phosphorylation of captured proteins is detected with biotinylated phospho-specific detection antibodies (Step 2) and then visualized using chemiluminescent detection reagents (Step 3) . (rndsystems.com)
  • Simultaneously detect the relative phosphorylation of these proteins in a single sample. (rndsystems.com)
  • Akt promotes cell survival by inhibiting apoptosis through phosphorylation and by inactivation of several targets, including Bad, forkhead transcription factor, c-Raf and caspase-9. (biolegend.com)
  • TGF-beta receptor type I then propagates the signal through phosphorylation of the SMAD family member ( SMAD ) proteins [ 2 ], [ 3 ]. (bio-rad.com)
  • These events result in the recruitment of p53 to PML NBs, p53 phosphorylation on Ser15, and activation of p53 target genes leading to the induction of apoptosis. (asm.org)
  • As a consequence of phosphorylation, the IκB-α protein is rapidly ubiquitinated on lysine residues 21 and 22 and degraded through the proteasome pathway, thereby allowing for migration of NF-κB to the nucleus, where it regulates the expression of a variety of genes involved in cell survival ( 6 , 52 ). (asm.org)
  • In particular, about 50% of cutaneous melanomas harbour B-RAF V600E mutations [ 2 ] that are responsible for the increased phosphorylation of extracellular activated protein kinases (ERKs) and increased expression of cyclin D1, which is associated with progression through G1/S phase of the cell cycle, as a partner of cyclin-dependent kinases (cdks) [ 3 ]. (hindawi.com)
  • Another signaling pathway activated by growth factor receptors involves the phosphorylation of signal transducers and activators of transcription (STAT). The duration and intensity of these signals are regulated by phosphatases and proteins that induce the activation of the JAK/STAT pathway, named suppressors of cytokine signaling (SOCS), and particularly SOCS1, a negative regulator of interleukin-6 (IL-6) and interferon (IFN-γ) signaling 8 . (nature.com)
  • Fas and TNFα receptor stimulation activates human STK38 by promoting phosphorylation at the hydrophobic motif. (thermofisher.com)
  • Activating phosphorylation of the Chk1 kinase was increased and total protein levels of CDC25C reduced, further implicating the DNA damage pathway in the induction of arrest. (core.ac.uk)
  • Immunoprecipitation and western blots were employed to determine protein-protein interactions, preotein levels, protein phosphorylation while immunofluorecesent staining for molecular co-localization. (biomedcentral.com)
  • The following pathway diagrams the early events of the cellular response after DSBs by IR through the activation of ATM in human cells. (wikipathways.org)
  • TGF-β-stimulated ERK signaling mediated regulation of 80 target genes not previously associated with this pathway. (pnas.org)
  • TNF-R1 activates Acid sphingomyelinase via pathway, which require TNFRSF1A-associated via death domain ( TRADD )/ Fas (TNFRSF6)-associated via death domain ( FADD ) adaptor proteins [ 5 ], [ 6 ]. (bio-rad.com)
  • And controversially, KSR / c-Raf-1 / MEK1(MAP2K1) [ 8 ]/ ERK1/2 [ 7 ] -dependent pathway can lead to inhibition of PI3K / v-akt murine thymoma viral oncogene homolog ( AKT(PKB) ) activation. (bio-rad.com)
  • The p53 pathway promotes efficient mitochondrial DNA base excision repair in colorectal cancer cells. (ohsu.edu)
  • In addition, expression of proteins within the MAPK signal transduction pathway was analyzed by Western blot. (biomedcentral.com)
  • As a serine-threonine protein kinase, BRAF plays an important role within the MAPK signaling pathway. (biomedcentral.com)
  • In many cases oncogenic RAS signalling through the RAF pathway engages an apoptotic response that is mediated by p53. (nih.gov)
  • Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-?B pathway. (abcam.com)
  • However, cell resistance to apoptosis may also be due to the activity of cytokine-dependent STAT-signaling pathway, including the high expression of survivin belonging to the family of inhibitors of apoptosis proteins (IAP). (intechopen.com)
  • Also, another cytokine-dependent signaling, an extrinsic apoptosis pathway associated with the family of tumor necrosis factor (TNF) receptors, has been investigated. (intechopen.com)
  • P53-mediated pathway of apoptosis plays a special role in aging, and its changes (excessive activation or suppression) cause severe pathologies, including neurodegenerative diseases and carcinogenesis. (intechopen.com)
  • Thus, we identify a major new Ras signaling pathway that links Ras to the control of specific protein acetylation and show how NORE1A allows Ras to qualitatively modify p53 function to promote senescence. (rupress.org)
  • RAF-1 (C-RAF-1), A-RAF, and B-RAF are all capable of activating the MEK1/2-ERK1/2 signaling pathway. (atlasgeneticsoncology.org)
  • Hsp90 inhibitors destabilize the binding of BCR-ABL protein thus leading to the formation of heteroprotein complex that is eventually degraded by the ubiquitin-proteasome pathway. (hindawi.com)
  • In ∼60% of melanomas, activation occurs through mutation of B-Raf (T1799A), an intermediate protein in the signaling pathway, resulting in kinase activity 10.7 times higher than occurs in normal cells ( 6 - 9 ). (aacrjournals.org)
  • The MAPK pathway is similarly activated in breast cancer cells with ∼100% having pathway activation due in part to aberrant Ras or Raf-1 activity ( 10 ). (aacrjournals.org)
  • The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase (MAP3K) that functions downstream of the Ras subfamily of membrane associated GTPases. (wikipedia.org)
  • Mutated Ras proteins remain longer in their active form than normal Ras proteins, resulting in an overstimulation of the proliferative pathway. (embl.de)
  • This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI 3-kinase. (biolegend.com)
  • However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. (nature.com)
  • To the best of our knowledge, the present study was the first to examine the expression levels of proteins associated with the Wnt signaling pathway in СD133+ CSCs of human GBM. (spandidos-publications.com)
  • The identified proteins were analyzed for their association with the Wnt signaling pathway using the international open databases PubMed, Protein Analysis Through Evolutionary Relationships, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Search Tool for the Retrieval of Interacting Genes/Proteins. (spandidos-publications.com)
  • An increased expression of 12 proteins associated with the Wnt signaling pathway were identified in GBM CD133+ CSCs, which included catenin β‑1, disheveled associated activator of morphogenesis 1, RAC family small GTPase 2 and RAS homolog gene family member A, a number of which are also associated with adherens junctions. (spandidos-publications.com)
  • In conclusion, these findings indicate Tan-IIA could inhibit AGS cells through decreasing the protein expression of EGFR, IGFR and blocking PI3K/AKT/mTOR pathway both in vitro and in vivo. (spandidos-publications.com)
  • The other may be through extrinsic apoptotic signaling pathway to induce apoptosis in vitro ( 22 , 23 ). (spandidos-publications.com)
  • We have identified a novel pathway of ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) signaling that results in nuclear factor κB (NF-κB) activation and chemoresistance in response to DNA damage. (asm.org)
  • Putting the pieces together: How is the mitochondrial pathway of apoptosis regulated in cancer and chemotherapy? (biomedcentral.com)
  • One goal of chemotherapy is to induce cancer cell death through the mitochondrial pathway of apoptosis. (biomedcentral.com)
  • The A-kinase anchoring protein 9- BRAF gene fusion, which is induced by the BRAF rearrangement through paracentric inversion of chromosome 7q, serves a role in activating the MAPK pathway in thyroid cancer ( 11 ). (spandidos-publications.com)
  • Although myotubularin was thought to be a dual-specificity protein phosphatase, recent results indicate that it is primarily a lipid phosphatase, acting on phosphatidylinositol 3-monophosphate, and might be involved in the regulation of phosphatidylinositol 3-kinase (PI 3-kinase) pathway and membrane trafficking. (embl.de)
  • The first category consists of small molecules targeting the most important signalling pathway in melanoma, mitogen-activated protein kinases (MAPK) pathway. (termedia.pl)
  • This pathway also regulates such tumour-promoting processes as growth, invasion, angiogenesis or resistance to therapy [5, 6]. (termedia.pl)
  • In melanoma, the MAPK pathway is activated mainly by mutation in B-Raf proto-oncogene (BRAF) and to a lesser extent by mutations in N-Ras proto-oncogene (NRAS) (15-30%) and KIT proto-oncogene receptor tyrosine kinase (c-KIT) (2-5%) [5, 7]. (termedia.pl)
  • Tumor-like tissue overgrowth results when apoptosis is prevented.We present evidence that Slik acts via Raf, but not via the canonical ERK pathway.Activation of Raf can compensate for the lack of Slik and support cell survival, but activation of ERK cannot. (nih.gov)
  • We present evidence that Slik acts via Raf, but not via the canonical ERK pathway. (nih.gov)
  • This phenotype is mediated by the Raf/MAPK pathway. (genetics.org)
  • The ER stress emerges as the common pathway that relates to apoptosis, atherosclerosis and neurological disorders and is modulated by levels of homocysteine. (biomedcentral.com)
  • B-Raf is a member of the mitogen-activated protein (MAP) kinase pathway whose activity is deregulated in melanomas by mutation to a constitutively active form called V600E B-Raf in approximately 90% of benign nevi or normal moles ( 9, 10 ). (aacrjournals.org)
  • However, the presence of V600E B-Raf alone does not cause melanoma as this aberrant protein activates the downstream MAP kinase pathway to inhibitory levels, leading to cellular senescence ( 10-16 ). (aacrjournals.org)
  • Other factors such as loss of tumor suppressors PTEN, p16 INK4a or activation of oncogenes such as Akt3 are needed to moderate V600E B-Raf activity and the downstream MAP kinase pathway to drive tumor progression ( 14-17 ). (aacrjournals.org)
  • Agell N, Bachs O, Rocamora N, Villalonga P (2002) Modulation of the Ras/Raf/MEK/ERK pathway by Ca(2+), and calmodulin. (springer.com)
  • MP2K1_HUMAN ] Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. (proteopedia.org)
  • Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. (proteopedia.org)
  • But specific point mutations in codon 12, 13, or 61 in one of the three Ras genes convert them into active oncogenes. (aacrjournals.org)
  • Ras gene mutations have been found in a variety of tumor types ( 18 ). (aacrjournals.org)
  • Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. (genecards.org)
  • Among these mutations, a single point mutation involving substitution of glutamate for valine at nucleotide 600 and resulting in mutant BRAF protein (BRAFV600E) is most common. (biomedcentral.com)
  • Oncogenic activation of these proteins owing to missense mutations is frequently detected in several types of cancer. (nih.gov)
  • This is largely attributable to activating mutations in Ras genes, but also to alterations in upstream components such as receptor tyrosine kinases that activate Ras ( 5 ). (aacrjournals.org)
  • RAS-RAF binding can be affected by 14-3-3 proteins and other scaffold/adaptor proteins kinase suppressor of RAS ( KSR ), the multidomain protein connector-enhancer of KSR (CNK), and the leucine-rich-repeat protein suppressor of RAS mutations-8 (SUR8), which cause formation of various homo- and heterodimers and subsequently affect signal transduction. (atlasgeneticsoncology.org)
  • Mutations in the RAF1 gene result in Noonan syndrome, Leopard syndrome and cardiomyopathy. (stjohnslabs.com)
  • Finally, the clinical applications provided by the understanding of the effects of MEN1 gene mutations on neuroendocrine tumor development in patients with this familial cancer syndrome are discussed. (springer.com)
  • The latter became the focus of research in recent years, since a large portion of human tumors carry oncogenic 'driver' mutations in the B-Raf gene. (wikipedia.org)
  • These mutations induce an uncontrolled, high activity of Raf enzymes. (wikipedia.org)
  • More than 90% of tumors harbor KRAS mutations, which are known to increase the tumor invasive ability by reprogramming pancreatic cell metabolism and promoting stromal reaction. (biomedcentral.com)
  • Squamous, pancreatic progenitor, and ADEX tumors were enriched in different mutations, such as TP53 and KDM6A, FOXA2/3, PDX1, and MNX1, and expressed preferentially at the early stage and with regulative genes involved in KRAS activation. (biomedcentral.com)
  • Many of these tumors also harbor additional mutations in genes that encode for epigenetic factors. (intechopen.com)
  • Activating mutations in oncogenes, such as BRAF and NRAS , and inactivating mutations in tumor suppressors genes, such as PTEN , promote this disease by altering cellular processes involved in growth, survival, and migration. (intechopen.com)
  • The cellular adaptations attributed to lung cancer include self-sufficient growth signals due to the occurrence of mutations in proto-oncogenes, lack of sensitivity to anti-proliferating signals as a result of mutations in tumor suppressor genes, evasion of apoptosis, unlimited replicative potential, detachment of tumor cells from the extracellular matrix, which leads to invasion of surrounding tissue and basal lamina. (biomedcentral.com)
  • However, B-RAF mutations alone are not sufficient to explain melanomagenesis since also benign nevi frequently have B-RAF mutations [ 4 , 5 ]. (hindawi.com)
  • Research studies have shown that mutations of the α-synuclein gene are linked to Parkinson's disease (1). (cellsignal.com)
  • Constitutive active mutations of Ras are frequently expressed in human cancers- ~ 20 to 30% of all human tumors contain one of the mutated Ras genes, especially in pancreas, thyroid and colon carcinomas (90, 60 and 45% respectively) [ 13 , 14 ]. (biomedcentral.com)
  • Several upstream modulators, cross-reacting oncogenes, and downstream effectors of NPM-ALK have been identified and characterized. (bloodjournal.org)
  • The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. (genecards.org)
  • C-Raf kinase and MEK are downstream effectors of the Ras signaling cascade. (biomedcentral.com)
  • The downstream effects of MEK1/2-ERK1/2 activation are varied, complex, and depend on the cellular context. (atlasgeneticsoncology.org)
  • Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. (aacrjournals.org)
  • A second, similar motif is found on the extreme C-terminus (centered around the phosphorylatable Ser 621) of all Raf enzymes, but downstream of the kinase domain. (wikipedia.org)
  • Their finding suggested that targeting downstream mediators or key nodal points might be more effective than targeting specific mutated genes. (biomedcentral.com)
  • This is defined as the transfer of phosphoryl groups [(PO3)2-] from one molecule to another, and serves as a transfer of energy that results in the activation, or deactivation of downstream proteins. (biolegend.com)
  • This suggested that the target molecule of GA is either downstream of v-src or an interacting protein. (pubmedcentralcanada.ca)
  • Multiple signaling proteins are activated downstream of these receptors, including the extracellular signal-related kinase (ERK)/MAP kinase, phosphatidyl-inositol-3′ (PI 3) kinase, and AKT. (rupress.org)
  • As described here, microscopic analysis of null mutants have revealed that the class I phosphoinositide 3-kinases, PIK1 and PIK2, and the downstream effector protein kinase B (PKB/Akt) are important in regulating completion of macropinocytosis. (embl.de)
  • This work demonstrates that it will be feasible to combine genetic and functional genomic approaches in the Drosophila hematopoietic system to systematically identify oncogene-specific downstream targets. (genetics.org)
  • ii ) Dominant-negative mutant forms of ζ were shown to inhibit ERK MAPK activation but increased the activation of JNK1 and p38 MAPK leading to increased apoptosis ( 31 ), and ( iii ) a dominant-negative η increased the basal activation of JNK1 and p38 MAPK and affected the ability of mice to compensate for pressure overload resulting in increased mortality, cardiomyopathy, and massive cardiomyocyte apoptosis ( 31 ). (pnas.org)
  • RAF activation leads to activation of the protein kinases MEK1 and MEK2 and subsequently the MAPK proteins ERK1 and ERK2 . (atlasgeneticsoncology.org)
  • The MAPK signaling cascade has been inhibited in both melanomas and breast cancer preclinical models using sorafenib (BAY 43-9006), which is a nonspecific Raf kinase inhibitor ( 14 , 15 ). (aacrjournals.org)
  • Most interestingly, Vemurafenib inhibited virus-induced apoptosis via impaired expression of apoptosis-inducing cytokines and led to hampered viral protein expression most likely due to the decreased activation of p38 and JNK MAPK. (frontiersin.org)
  • However, in addition to these, the variety of stimuli and the specific expression of proteins in the different cell types increase the complexity of MAPK system [ 4 ]. (mdpi.com)
  • One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. (proteopedia.org)
  • Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to a. (genecards.org)
  • It is an endogenous inhibitor of RAF KINASES and may play a role in regulating SIGNAL TRANSDUCTION. (labome.org)
  • The dynamic process of signal transduction involves the concerted action of both protein kinases and protein phosphatases. (embopress.org)
  • Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. (uniprot.org)
  • SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. (uniprot.org)
  • C-Raf is a member of the Raf kinase family of serine/threonine-specific protein kinases, from the TKL (Tyrosine-kinase-like) group of kinases. (wikipedia.org)
  • Several years later after the discovery of c-Raf, two further related kinases were described: A-Raf and B-Raf. (wikipedia.org)
  • Thus diagnostic and therapeutic interest in Raf kinases reached a new peak in the recent years. (wikipedia.org)
  • But unlike PKC, the C1 domains of Raf family kinases do not bind diacylglycerol. (wikipedia.org)
  • Three concepts are of particular importance: (1) formation of free radicals, (2) assumed inhibition of tyrosine kinases, and (3) binding to and interference with the function of members of the Hsp90 family of proteins. (pubmedcentralcanada.ca)
  • The Akt family of kinases are activated by growth factors and regulate pleiotropic cellular activities. (rupress.org)
  • Phosphatidylinositol 3-kinases are a family of dual specificity lipid/protein kinases. (embl.de)
  • Lipid kinases and their phosphorylated products are important regulators of many cellular processes, including intracellular membrane traffic. (embl.de)
  • In this context, we have observed that the signaling molecule Raf-1 can physically interact with the Rb protein in response to proliferative signals and inactivate it independent of cyclins and cyclin dependent kinases. (moffitt.org)
  • RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. (proteopedia.org)
  • Akt, also known as Protein Kinase B (PKB), is a serine/threonine-specific protein kinase that plays an integral role in mediating signals for cell growth, survival, cell-cycle progression, differentiation, transcription, translation, and glucose metabolism. (rockland-inc.com)
  • ΔN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival. (ohsu.edu)
  • The mRNA expression levels of ENTPD7 in different lung cancer stages were determined using TCGA, and weighted gene co-expression network analysis (WGCNA) was applied to conduct correlation analysis of the expressions of ENTPD7 and survival rate. (biomedcentral.com)
  • Activation of NF κ B and inhibition of p53 and BAD by AKT evade apoptosis and promote CML cells survival. (hindawi.com)
  • In this way, GSH compartmentalization within the cell has consequences for the activity of proteins that promote cell survival (see Fig. 1 ). (aspetjournals.org)
  • Akt plays a critical role in controlling survival and apoptosis. (biolegend.com)
  • Oncogenic proteins normally function in homeostatic proliferative and survival mechanisms, but due to mutation (e.g. (biomedcentral.com)
  • Dr. Cleveland's research has been broadly focused on the molecular pathogenesis of cancer, where he has been a leader in interrogating the regulation and role of oncogenes and tumor suppressors in controlling cancer cell growth and survival, and in defining new targets that play essential roles in the development and maintenance of cancer. (moffitt.org)
  • This is particularly important during cellular response to stress that may lead to apoptosis by providing cells with a fine tuning mechanism that tips the balance between cell survival or apoptosis. (exp-oncology.com.ua)
  • At normal levels, Slik provides survival cues that prevent apoptosis. (nih.gov)
  • Cells deprived of Slik activity can grow, divide, and differentiate, but have an intrinsic survival defect and undergo apoptosis even under conditions in which they are not competing with normal cells for survival cues. (nih.gov)
  • Activation of Raf can compensate for the lack of Slik and support cell survival, but activation of ERK cannot. (nih.gov)
  • Bcl-2 promotes cell survival by blocking programmed cell death (12-14). (isciii.es)
  • 2002). A DNA damage-regulated BRCT-containing protein, TopBP1, is required for cell survival. (core.ac.uk)
  • N terminus of ASPP2 binds to Ras and enhances Ras/Raf/MEK/ERK activation to promote oncogene-induced senescence. (ohsu.edu)
  • In response to DNA damage cells can activate the DNA damage checkpoints to transiently arrest and restore the integrity of the genome, enter a state of irreversible arrest (senescence) or undergo apoptosis. (nih.gov)
  • Involvement of Lamin B1 Reduction in Accelerated Cellular Senescence during Chronic Obstructive Pulmonary Disease Pathogenesis. (abcam.com)
  • Gu and Zhu, 2012 ), biasing it toward apoptosis or senescence. (rupress.org)
  • Selected stimuli may induce phenotypes suggesting senescence, including mitogenic oncogene activation or ionizing radiation (5-8). (isciii.es)
  • Elevated Akt3 activity, occurs in approximately 70% of melanomas and inhibits V600E B-Raf protein activity by phosphorylating negative regulatory sites, which moderates protein activity to levels promoting melanoma development rather than driving cells into senescence ( 10 , 15 , 17-20 ). (aacrjournals.org)
  • Therefore, therapeutics targeting Akt3 activity has potential to increase MAP kinase activity to inhibitory levels to promote cell senescence. (aacrjournals.org)
  • MBS077112 is a ready-to-use microwell, strip plate Sandwich (Quantitative) ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the C-Raf Proto Oncogene Serine/Threonine Protein Kinase (CRAF) ELISA Kit target analytes in biological samples. (mybiosource.com)
  • RAF1 (Raf-1 Proto-Oncogene, Serine/Threonine Kinase) is a Protein Coding gene. (genecards.org)
  • We have recently shown overexpression of a core splice regulatory protein, serine-arginine protein kinase 1 (SRPK1), in dysplastic and neoplastic pancreatic ductular cells. (aacrjournals.org)
  • We recently reported the elevation of a kinase [serine-arginine protein kinase (SRPK) 1] in pancreatic carcinoma cells that is critical for the regulation of various mRNA splicing factors ( 1 ). (aacrjournals.org)
  • Protein phosphatase 2A (PP2A), a major protein serine/threonine phosphatase in most mammalian tissues, is implicated in the regulation of various cellular processes, such as cell growth and transformation (reviewed in Mumby and Walter, 1993 ). (embopress.org)
  • The RAF proteins share three conserved domains: two (CR1 and CR2) in the N terminus and a third (CR3-encoding for the serine/threonine kinase domain) in the C terminus. (atlasgeneticsoncology.org)
  • RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the RAF1 gene. (wikipedia.org)
  • Researchers were able to demonstrate that these genes encode enzymes that have serine-threonine kinase activity. (wikipedia.org)
  • It is highly enriched in serine amino acids, but its precise sequence is poorly conserved across related Raf genes. (wikipedia.org)
  • This hinge region contains a small, conserved island of amino acids, that are responsible for 14-3-3 protein recognition, but only when a critical serine (Ser259 in human c-Raf) is phosphorylated. (wikipedia.org)
  • AHR activation induces the expression of resistance genes against the inhibitors of V600E mutated B-Raf proto-oncogene, serine/threonine kinase (BRAF) in melanoma and upregulation of programmed cell death protein 1 (PD-1) in tumor-infiltrating T cells surrounding melanoma. (frontiersin.org)
  • In particular, the emergence of molecular targeted therapies including inhibitors for V600E mutated B-Raf proto-oncogene, serine/threonine kinase (BRAF) and checkpoint inhibitors, which attenuate suppression of the anti-tumor immune response, have drastically improved the outcome of advanced melanoma. (frontiersin.org)
  • Akt (also known as protein kinase B alpha) is a 60 kD serine/threonine specific kinase containing a pleckstrin domain. (biolegend.com)
  • STK38 (also known as NDR) or Nuclear Dbf2-related protein is a serine/threonine kinase in the subgroup of the AGC kinase family that is regulated by Mob proteins. (thermofisher.com)
  • The complex interaction of the activated receptor with other proteins inside the cell before the ultimate physiological effect of the ligand on the cell's behavior is produced is called signal transduction or cell signaling. (rockland-inc.com)
  • The 14-3-3 proteins are involved in the regulation of metabolism, signal transduction, cell-cycle control, apoptosis, protein trafficking, transcription, stress responses, and malignant transformation ( 5 , 6 ) mainly through binding to phosphopeptides, thus modulating signaling events. (pnas.org)
  • The Ras protein is involved in signal transduction: it passes on stimuli from extracellular factors to the cell nucleus, thereby changing the expression of a number of growth regulating genes. (embl.de)
  • For the study of biological signal transduction, access to correctly lipidated proteins is of utmost importance. (embl.de)
  • This result highlights the usefulness of these compounds as invaluable tools for the study of Ras signal transduction processes and the plasma membrane localization of the Ras proteins. (embl.de)
  • Aronin N, DiFiglia M (1992) The subcellular localization of the G-protein Gi alpha in the basal ganglia reveals its potential role in both signal transduction and vesicle trafficking. (springer.com)
  • Notch signaling involves gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. (rockland-inc.com)
  • Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. (genecards.org)
  • TGF-β may inhibit cell cycle progression through regulation of cyclin-dependent kinase inhibitors p15 INK4B , p21 CIP1 , and p27 KIP1 ( 8 , 9 ) and induces apoptosis via activation of caspases ( 10 ). (pnas.org)
  • For example, partial inhibition of TGF-β type II receptor function results in loss of growth inhibition but not regulation of matrix genes by TGF-β ( 13 ). (pnas.org)
  • Baritaki S, Katsman A, Chatterjee D, Yeung K, Spandidos D, Bonavida B. Regulation of tumor cell sensitivity to TRAIL-induced apoptosis by the metastatic suppressor Raf kinase inhibitor protein via Yin Yang 1 inhibition and death receptor 5 up-regulation. (labome.org)
  • We use a combination of genetic, molecular, and cellular approaches to analyze the regulation and importance of FOXO transcription factors, and more generally 'longevity genes' in mammals. (stanford.edu)
  • SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). (uniprot.org)
  • This study reveals the molecular regulation mechanisms of neurosecretory cell apoptosis in physiological and pathological (oncogene human epidermal growth factor receptor (HER)-2/Neu overexpression) aging. (intechopen.com)
  • This will reveal the general trends of regulation of neurosecretory cell apoptosis during aging. (intechopen.com)
  • Similarly to many other MAPKKKs, c-Raf is a multidomain protein, with several additional domains to aid the regulation of its catalytic activity. (wikipedia.org)
  • a-synuclein may be involved in the regulation of dopamine release and transport and also may function to induce fibrillization of microtubule-associated protein tau. (biolegend.com)
  • Calcyclin‑binding protein, casein kinase II α, casein kinase II β, CtBP1, CtBP2, CUL1 and RUVBL1 proteins may be used as targets for the pharmaceutical regulation of CSCs in complex GBM treatment. (spandidos-publications.com)
  • In contrast, Akt1 down-regulation in IGF-IR-stimulated cells promoted dramatic neomorphic effects characteristic of an epithelial-mesenchymal transition (EMT) and enhanced cell migration induced by IGF-I or EGF stimulation. (rupress.org)
  • SMAD s can bind DNA directly with low affinity and specificity and thus rely on interactions with other DNA-binding proteins to target specific genes for transcriptional regulation, for example Forkhead box H1 ( FAST-1/2 ) [ 8 ]. (bio-rad.com)
  • MicroRNAs (miRNAs), a class of short RNAs, play key roles in various biological processes and in the development of human disease by post-transcriptional regulation of gene expression. (physiology.org)
  • Regulation of protein synthesis, although known for many decades, has only recently begun to be recognized as a critical control mechanism for the maintenance of cellular homeostasis and cellular stress response. (exp-oncology.com.ua)
  • The regulation of gene expression occurs at many levels including the transcriptional and translational steps. (exp-oncology.com.ua)
  • The major research interest is to understand the mechanisms by which extra-cellular signals regulate the cell cycle machinery and how a loss of this regulation leads to oncogenesis. (moffitt.org)
  • The comprehensive network collated has lead to the identification of genes that are modulated by homocysteine indicating that homocysteine exerts its effect not only through modulating the substrate levels for various catalytic processes but also through regulation of expression of genes involved in complex diseases. (biomedcentral.com)
  • AGS and related proteins provide unexpected insights into the regulation of the G-protein activation-deactivation cycle. (springer.com)
  • These proteins play important roles in the generation or positioning of signaling complexes and of the regulation of GPCR signaling, and as alternative binding partners for G-protein subunits. (springer.com)
  • The name is due to its molecular mass: it is in the 53 kilodalton fraction of cell proteins. (rockland-inc.com)
  • My major research interest is investigating the basic cellular and molecular mechanisms of how tumors form and respond to treatment. (ohsu.edu)
  • CMGH Cellular and Molecular Gastroenterology and Hepatology In: , Vol. 3, No. 2, 01.03.2017, p. 163-173. (ohsu.edu)
  • The classical mitogenic cascade transmits stimuli from growth factor receptors via Ras, Raf, MEK and ERK to the cell nucleus and provides attractive molecular targets for cancer treatment. (biomedcentral.com)
  • Heat-shock proteins (Hsps) function as molecular chaperones facilitating proper folding of nascent polypeptides. (hindawi.com)
  • When compared to mAbs which are usually large molecular weight proteins of around 150kDa, small molecule cancer drugs are much smaller in size (≤500Da) and thus can translocate through plasma membranes. (oatext.com)
  • In addition, it is desirable to attempt to relate the antitumor activity of a candidate compound with molecular effects on proteins relevant for the pathogenesis of malignant diseases. (pubmedcentralcanada.ca)
  • Molecular studies revealed the binding of GA to members of the heat shock protein 90 (Hsp90) family of molecular chaperones ( Whitesell et al 1994 ). (pubmedcentralcanada.ca)
  • An understanding of the mutated oncogenes, genetic alterations and the cellular adaptations has paved the road for identifying molecular therapeutic targets. (biomedcentral.com)
  • Dr. Cleveland has also served as an Editor for several prestigious journals, including Molecular Biology of the Cell and Molecular and Cellular Biology, and as an Associate Editor for Cell Death and Differentiation and for Cancer Research. (moffitt.org)
  • mTORC1, the molecular target of the immune-suppressant rapamycin, phosphorylates unc-51-like kinase 1 (ULK1) to repress autophagy and promote protein synthesis by phosphorylating the p70 (RPS6KB1) subunit of S6 kinase (S6K) and the eukaryotic initiation factor 4E-binding proteins (4EBPs) ( Laplante and Sabatini, 2012 ). (biologists.org)
  • Current molecular mechanisms of cholangiocarcinogenesis focus on growth regulatory genes and chronic biliary inflammation. (iiarjournals.org)
  • The aim of this paper is to review the major events involved in apoptosis, their causes at both the molecular and cellular level, and their pathologic consequences, focusing on H. pylori -induced apoptosis in gastric mucosal epithelial cells as well as on bacterial strains. (isciii.es)
  • Ras proteins are small GTPases that act as molecular switches by cycling between inactive GDP-bound and active GTP-bound states. (biomedcentral.com)
  • The molecular chaperone Heat Shock Protein-90 (Hsp90) may offer an ideal treatment target, as it is a critical signaling hub in urothelial carcinoma pathogenesis and potentiates chemoradiation. (oncotarget.com)
  • CM363 revealed an effective cell growth inhibition (IC50 = 0.7 ± 0.5 μM) by inducing cancer cells to undergo cell cycle arrest and apoptosis. (oncotarget.com)
  • In this study, we show that inhibition of NF-κB activity in melanocytes that are persistently expressing an active H-Ras V12 gene and are deficient in the tumor suppressors inhibitor A of cyclin-dependent kinase 4/alternative reading frame results in reduction of melanoma tumor growth in vivo . (aacrjournals.org)
  • This inhibition depends on protein phosphatase 2 ( PP2A )-mediated dephosphorylation and by blocking AKT(PKB) translocation to plasma membrane via Protein kinase C zeta ( PKC-zeta ). (bio-rad.com)
  • We have reported that inhibition of protein phosphatase 2A (PP2A) by expression of SV40 small t stimulates the mitogenic MAP kinase cascade. (embopress.org)
  • Constitutive activation of PKC ζ and NF‐κB following inhibition of PP2A supports new mechanisms by which SV40 small t promotes cell growth and transformation. (embopress.org)
  • Ras inhibition by farnesylthiosalicylic acid or by a dominant-negative Ras also led to complete disappearance of MycN protein from the nuclei of LAN-1 cells. (aacrjournals.org)
  • In vivo , an ∼30% increase in tumor inhibition compared with sorafenib treatment alone and an ∼58% reduction in tumor size compared with nanoliposomal ceramide monotherapy occurred by doubling apoptosis rates with negligible systemic toxicity. (aacrjournals.org)
  • Inhibition of the farnesylation of RhoB results in growth blockade of the exposed tumor cells as well as an increase in the rate of apoptosis. (embl.de)
  • Primary hepatocytes were treated with TNF-a, Staurosporine and LY294002, protein-kinase inhibitors, in order to evaluate the activation and/or the inhibition of these mediators in the apoptotic process. (unipd.it)
  • Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. (nature.com)
  • TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF -mutant melanoma. (nature.com)
  • Mutated, constitutively active B-RAF is believed to play a crucial role, although the selective B-RAF inhibition has shown poor clinical success, since phenomena of resistance usually occur, likely arising from additional genetic aberrations, such as loss of function of p53 and PTEN, overexpression of cyclin D1, hyperactivation of NF- κ B, and downregulation of p21/Cip1. (hindawi.com)
  • As the possible mechanisms of resistance to double B-RAF and MEK inhibition is concerned, it must be kept in mind that the activated Ras/Raf/MEK/ERK cascade can lead to opposite proliferative responses. (hindawi.com)
  • Therefore, the possibility that the simultaneous inhibition of B-RAF and ERK rather suppresses an antiproliferative stimulus must be considered. (hindawi.com)
  • This study explores the impact of heat shock protein 90 (Hsp90) inhibition in combination with focal adhesion kinase (FAK) inhibitor on the growth of non-small cell lung cancer cells (NSCLC cells). (impactjournals.com)
  • Transformation by oncogene Ras overcomes TGF-β mediated growth inhibition in epithelial cells. (biomedcentral.com)
  • RAF1: a proto-oncogenic TKL kinase of the RAF family. (mybiosource.com)
  • This chromosomal translocation induces the formation of the chimeric protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which possesses significant oncogenic potential resulting from the constitutive activation of the tyrosine kinase ALK. (bloodjournal.org)
  • Oncogenic RAS establishes independence from extracellular growth factors and growth inhibitors, thereby promoting exit from the G0 phase of the cell cycle, progression through G1 and entry into S phase. (nih.gov)
  • Should an oncogenic protein, such as those produced by cells infected by high-risk types of human papillomavirus, bind and inactivate pRb, this can lead to cancer. (wikipedia.org)
  • The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. (springer.com)
  • These genetic and epigenetic alterations result in DNA damage and cellular adaptations to tolerate the oncogenic changes [ 8 ]. (biomedcentral.com)
  • We show that oncogenic H-Ras and N-Ras engage Raf-1 on the Golgi and that endogenous Ras and unpalmitoylated H-Ras are activated in response to mitogens on the Golgi and endoplasmic reticulum (ER), respectively. (jove.com)
  • Ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase) family consists of eight members that regulate extracellular Adenosine Triphosphate (ATP) level and participates in cellular activities [ 16 ]. (biomedcentral.com)
  • They are activated by extracellular signals that promote guanine-nucleotide exchange factor-mediated exchange of GDP for GTP on Ras ( 2 ). (aacrjournals.org)
  • Binding of various extracellular ligands such as growth factors and hormones activates RAS and subsequently RAF proteins. (atlasgeneticsoncology.org)
  • d) BCR-ABL phosphorylate cytoskeleton proteins resulting in increased cellular motility and reduced adhesion to extracellular matrix of bone marrow. (hindawi.com)
  • the tumor microenvironment plays a key role in treatment resistance because it creates a mechanical barrier consisting of dense stroma with fibroblasts, leukocytes, hyaluronic acid (HA), cancer stem cells (CSCs), collagen, and some extracellular matrix protein, resulting in hypoxia and anti-angiogenesis, which promotes carcinogenesis, facilitates tumor progression and induces chemotherapeutic resistance. (biomedcentral.com)
  • It has a key regulatory role in the production of reactive oxygen species, cell cycle, heme homeostasis, hematopoiesis, and immunity and has been shown to suppress ischemic angiogenesis and promote breast cancer metastasis. (hindawi.com)
  • b) BCR-ABL phosphorylates adaptor proteins like CRK and CRKL leading to the activation of PI3-K. PI3-K phosphorylates PIP2 to PIP3 which in turn activates AKT. (hindawi.com)
  • Pore formation is referred to as mitochondrial outer membrane permeabilization (MOMP), and this results in the release of mitochondrial proteins (e.g., cytochrome c) that cooperate with cellular adaptor proteins (i.e. (biomedcentral.com)
  • Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. (genecards.org)
  • A ubiquitously found basic protein that binds to phosphatidylethanolamine and NUCLEOTIDES. (labome.org)
  • This primary antibody specifically binds to endogenous Raf-1 protein which only binds about S259 when S259 is phosphorylated. (stjohnslabs.com)
  • Although its common function is seen as binding and repressing E2F targets, Rb is likely a multifunctional protein as it binds to at least 100 other proteins. (wikipedia.org)
  • Rb binds and inhibits E2 promoter-binding-protein-dimerization partner (E2F-DP) dimers, which are transcription factors of the E2F family that push the cell into S phase. (wikipedia.org)
  • The mature protein subsequently binds to one of six binding proteins and is then secreted form the tissue of origin ( IGFBP1 , IGFBP2 , IGFBP3 , IGFBP4, IGFBP5, IGFBP6 ). (atlasgeneticsoncology.org)
  • The N-terminal region of Bach1 contains a BTB/POZ domain, which functions as a protein interaction motif, while the C-terminal bZip domain binds to DNA [ 1 ] and mediates the heterodimerization of Bach1 with small Maf proteins (e.g. (hindawi.com)
  • The Ras-binding domain displays a ubiquitin-like fold (like many other small G-protein associating domains) and selectively binds GTP-bound Ras proteins only. (wikipedia.org)
  • Geldanamycin (GA) is an ansamycin antibiotic that binds and inhibits the ATP dependent function of Hsp90 preventing the folding of client proteins, and many inhibitors used are based on the GA structure [ 8 - 12 ]. (impactjournals.com)
  • Excess homocysteine is exported into circulation where it rapidly binds to proteins and other small molecules like cysteine. (biomedcentral.com)
  • In some cases, the risk of developing melanoma runs in families, where a mutation in the CDKN2A gene on chromosome 9p21 can underlie susceptibility to melanoma ( 12 , 13 ). (aacrjournals.org)
  • Thus, loss/inactivation of the INK4a/ARF gene was postulated a contributor of the pathogenesis of melanoma in a NF-κB-dependent manner. (aacrjournals.org)
  • However, in cooperation with an active oncogene, such as H-ras, INK4a/ARF −/− melanocytes progress into melanoma ( 17 ). (aacrjournals.org)
  • Park S, Yeung M, Beach S, Shields J, Yeung K. RKIP downregulates B-Raf kinase activity in melanoma cancer cells. (labome.org)
  • The low expression of RKIP and its antagonistic action on B-Raf suggests that RKIP may play an important role in melanoma turmorgenesis. (labome.org)
  • Indeed, AHR is a susceptibility gene for squamous cell carcinoma and a prognostic factor for melanoma and Merkel cell carcinoma. (frontiersin.org)
  • Prominent genetic alterations in epigenetic regulator genes in cutaneous melanoma. (intechopen.com)
  • The oncogenes BRAF and NRAS are altered in 51% and 31% of the 278 melanoma tumor samples, respectively. (intechopen.com)
  • Accumulating evidence strongly suggests that the pathogenesis of melanoma is also shaped by the aberrant activity of epigenetic factors that regulate gene expression through the modification of DNA and chromatin. (intechopen.com)
  • Silencing of SOCS1 protein with shRNAi lentivirus (shR-SOCS1) led to partial reversion of the tumorigenic phenotype of B16F10-Nex2 melanoma cells. (nature.com)
  • No agent targeting Akt3 or V600E B-Raf signaling involved in early melanoma development is available clinically to prevent the disease or retard early stage noninvasive melanocytic lesion cells from progressing into metastatic melanoma ( 6 ). (aacrjournals.org)
  • Therefore, very few V600E B-Raf containing moles ever develop into melanoma and remain in a senescent stage ( 14, 15 ). (aacrjournals.org)
  • A major role is that of the MRN (MRE11/RAD50/NBS1) complex binding to DSBs and facilitating the activation of ATM (Ataxia Telangiectasia Mutated) protein, a key PI3K (Phosphatidylinositol 3-kinase) related kinase in the DNA damage response (DDR). (wikipathways.org)
  • Similarly, persistent activation of Ras and Raf proteins that activate ERK is sufficient to promote EMT and contributes to invasiveness and metastasis formation in carcinomas with activated ras oncogenes ( 22 ). (pnas.org)
  • Hyperproliferative cues from activation of the RAS oncogene can result in replicative stress leading to DNA damage. (nih.gov)
  • Also, signalling through the RAS effectors RASSF1, NORE1, mammalian STE20-like protein kinase 1 (MST1) and JUN N-terminal kinase (JNK) can lead to apoptotic death via the activation of caspase 3 and the pro-apoptotic proteins BCL-2-associated X protein (BAX) and BCL-2-homologous antagonist/killer 1 (BAK1). (nih.gov)
  • These include activation of transcription factors, expression of specific cell-surface proteins, reorganization and expression of cytoskeletal proteins, production of ECM-degrading enzymes, and changes in the expression of specific microRNAs. (jci.org)
  • In this chapter, we consider the participation of p53-regulating genes and p53 target genes in activation of this cascade during physiological aging, as well as suppression under HER-2/Neu overexpression. (intechopen.com)
  • These cascades are involved in both the activation of apoptosis and its suppression. (intechopen.com)
  • Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. (stjohnslabs.com)
  • In this review, we will summarize recent contributions to our understanding of the importance of cytotoxic drug-induced modulation of cellular redox status for signaling and transcription leading to activation of apoptotic effector mechanisms. (aspetjournals.org)
  • Treatment of B-Raf WT cells with Vemurafenib induced a hyperactivation of the Raf/MEK/ERK cascade rather than inhibiting its activation upon IAV infection. (frontiersin.org)
  • In addition, the carcinogenic effects of ultraviolet (UV) and chemical carcinogens, both of which are major environmental carcinogenetic factors of skin, are at least partly mediated by AHR, which regulates UV-induced inflammation and apoptosis, the DNA repair system, and metabolic activation of chemical carcinogens. (frontiersin.org)
  • however, the high expression levels of adenomatous polyposis coli, β‑catenin, C‑terminal binding protein (CtBP) and RuvB‑like AAA ATPase 1 (RUVBL1 or Pontin52) proteins suggest the possibility of alternative activation of specific genes in the nuclei of these cells. (spandidos-publications.com)
  • SMAD3 -mediated Anaphase-promoting complex with Fizzy/cell division cycle 20 related 1 ( APC/hCDH1 complex ) activation leads to degradation of SnoN [ 9 ]. (bio-rad.com)
  • TGF-beta induces transcription of the human SMAD7 gene through activation of SMAD3 [ 12 ], and transcription factor Ets variant gene 1 ( ER81 ) [ 13 ]. (bio-rad.com)
  • Previously, two independent studies have reported an essential role of the ataxia telangiectasia (A-T) mutated (ATM) gene during NF-κB activation following IR or CPT-induced DSBs ( 24 , 38 ). (asm.org)
  • In addition, an inflammatory response, characterized primarily by the recruitment of monocytes and macrophages, promotes vascular remodeling through the activation of SMCs ( 70 , 72 , 73 , 92 ). (physiology.org)
  • Growth factor receptors activate mTOR by driving RAS, phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB)-dependent signals that converge to inhibit the tuberous sclerosis 1 and 2 heterodimer (TSC1 and TSC2) leading to activation of the small GTPase RHEB. (biologists.org)
  • PhosphoPlus® Duets from Cell Signaling Technology (CST) provide a means to assess protein activation status. (cellsignal.com)
  • Each Duet contains an activation-state and total protein antibody to your target of interest. (cellsignal.com)
  • 1988). Activation at Mphase of a protein kinase encoded by a starfish homologue of the cell cycle control gene cdc2+. (core.ac.uk)
  • 2009). Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells. (core.ac.uk)
  • 2005). Activation of PPARγ by curcumin inhibits Moser cell growth and mediates suppression of gene expression of cyclin D1 and EGFR. (core.ac.uk)
  • Bernard ML, Peterson YK, Chung P., Jourdan J, Lanier SM (2001) Selective interaction of AGS3 with G-proteins and the influence of AGS3 on the activation state of G-proteins. (springer.com)
  • This gene is the cellular homolog of viral raf gene (v-raf). (genecards.org)
  • Ceramides signaling in some cases was shown to be dependent on v-Ha-ras Harvey rat sarcoma viral oncogene homolog ( H-Ras ) [ 8 ], [ 10 ]. (bio-rad.com)
  • It is now generally acknowledged that HBx supplied in trans can increase gene expression of a wide variety of viral and cellular promoters and enhancer elements [ 11 , 12 ]. (biomedcentral.com)
  • AKT (v-akt murine thymoma viral oncogene homolog 1) and N-Ras (neuroblastoma ras viral oncogene homolog) coactivation in the mouse liver promotes r. (nih.gov)
  • To investigate this issue, we generated a mouse model characterized by combined overexpression of activated forms of AKT and neuroblastoma Ras viral oncogene homolog (N-Ras) protooncogenes in the liver by way of hydrodynamic gene transfer. (nih.gov)
  • V-ski sarcoma viral oncogene homolog ( Ski ) and SKI-like oncogene ( SnoN ) modulate the nuclear activity of SMAD and function as corepressors antagonize TGF-beta signaling [ 4 ], [ 8 ]. (bio-rad.com)
  • In contrast with epithelial homeostasis, TGF-β signals appear to promote tumor progression in advanced carcinomas. (pnas.org)
  • The 14-3-3 proteins have been found to be up- or down-regulated in human disease, but their direct role in disease progression has not been clearly established. (pnas.org)
  • Once released, E2F transcription factors transactivate several genes that are required for cell cycle progression, including cyclin E ( CCNE ) and cyclin A ( CCNA ) that induce transition through the G1/S checkpoint (not shown). (nih.gov)
  • Active Ras is needed to block MycN degradation, promoting cooperative Ras- and MycN-dependent cell cycle progression in LAN-1 cells. (aacrjournals.org)
  • In this case, should a cell sustain only one mutation in the other RB gene, all Rb in that cell would be ineffective at inhibiting cell cycle progression, allowing cells to divide uncontrollably and eventually become cancerous. (wikipedia.org)
  • A recent avenue of research has been on the role of nicotinic receptor signaling in lung cancer, especially how exposure to nicotine promotes the growth and progression of tumors and renders them resistant to death induced by chemotherapeutic drugs. (moffitt.org)
  • Thus, TGF-β acts as a tumor suppressor in early tumor development, but promotes tumor invasion and metastasis during late stages of tumor progression [ 11 ]. (biomedcentral.com)
  • Our laboratory evaluated cellular phenotypic effects in response to treatment with PLX4032, a BRAFV600E-specific inhibitor, in normal BRAF-wild-type thyroid cells and in BRAFV600E-positive papillary thyroid cancer cells. (biomedcentral.com)
  • As a potential therapeutic target, the BRAF mutation plays a central role in promoting aggressive phenotype of thyroid cancer and is associated with worse prognosis. (biomedcentral.com)
  • Subsequently, B-Raf and A-Raf-1 paralogues ( BRAF , located in Xq13 and ARAF , located in Xp11) were discovered. (atlasgeneticsoncology.org)
  • Oncogene mimicry as a mechanism of primary resistance to BRAF inhibitors. (nature.com)
  • Once activated Raf-1 can phosphorylate and activate MEK1/2, which in turn phosphorylate and activate ERK1/2. (mybiosource.com)
  • Active RAF stimulates MEK1, which in turn activates ERK1/2. (hindawi.com)
  • Subsequent experiments showed that the normal, cellular Raf genes can also mutate to become oncogenes, by "overdriving" MEK1/2 and ERK1/2 activity. (wikipedia.org)
  • c-Raf-1 was the first successfully cloned functional human homolog of the v-Raf gene, and thus the gene product of c-Raf-1 has historically been referred to in the literature simply as Raf-1. (atlasgeneticsoncology.org)
  • Isolation, genomic organization and expression analysis of Men 1, the murine homolog of the MEN1 gene. (springer.com)
  • Recent advances in Akt signaling have focused on understanding even more cellular processes and identifying cellular substrates that are physiologically relevant in vivo . (rockland-inc.com)
  • Proteins encoded by splice variants have been shown to affect a variety of tumor-associated processes. (aacrjournals.org)
  • In this Review, we describe how RAS oncogenes exploit their extensive signalling reach to affect multiple cellular processes that drive tumorigenesis. (nih.gov)
  • HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. (biomedcentral.com)
  • This review summarizes how Bach1 controls these and other cellular and physiological and pathological processes. (hindawi.com)
  • Loss of cell cycle control can result in pathological processes such as cellular transformation (reviewed in reference 47 ). (asm.org)
  • An overview of complex cellular processes like drug tolerance can be achieved with proteomic studies. (elsevier.es)
  • The protein is a receptor tyrosine kinase located on the plasma membrane of cells. (rockland-inc.com)
  • The BCR-ABL oncogene encodes a constitutively activated tyrosine kinase, BCR-ABL. (hindawi.com)
  • miRNA-21 , Protein tyrosine phosphatase gene ( PTEN ), Ventilator associated pneumonia (VAP), Lung trauma. (alliedacademies.org)
  • Protein Tyrosine Phosphatase Gene ( PTEN ) is an important gene in human and it has been wildly studied in tumors. (alliedacademies.org)
  • EGFR is a transmembrane protein belonging to the ErbB family of receptors, which functions as a receptor tyrosine kinase (RTK). (springer.com)
  • Among 609 differentially expressed genes, c-Kit, Met and EphA3 cytokine/tyrosine-kinase (TK) receptors were down regulated. (nature.com)
  • The myotubularin-related genes define a large family of eukaryotic proteins, most of them initially characterized by the presence of a ten-amino acid consensus sequence related to the active sites of tyrosine phosphatases, dual-specificity protein phosphatases and the lipid phosphatase PTEN. (embl.de)
  • Menin, a gene product responsible for multiple endocrine neoplasia type 1, interacts with the putative tumor metastasis protein nm23. (springer.com)
  • These results suggest that p27 +/− mammary epithelium may be more susceptible to oncogene-induced tumorigenesis, whereas p27 -null glands, due to severely impaired cyclin D1/Cdk4 function, are more resistant to transformation. (asm.org)
  • E2F1 regulates the base excision repair gene XRCC1 and promotes DNA repair. (ohsu.edu)
  • The tumor suppressor menin regulates hematopoiesis and myeloid transformation by influencing Hox gene expression. (springer.com)
  • After export into the cytoplasm, Bach1 forms fiber-like structures on microtubules by colocalizing with intracellular hyaluronic acid-binding protein (IHABP), which regulates the subcellular localization of Bach1 [ 13 ]. (hindawi.com)
  • Owens TW, Gilmore AP, Streuli CH, Foster FM (2013) Inhibitor of Apoptosis Proteins: Promising Targets for Cancer Therapy. (omicsonline.org)
  • p53 is a key mediator of the cellular response to a broad variety of stress stimuli ( Levine, 1997 ). (rupress.org)
  • PTEN plays a key role in cell apoptosis, cell cycle and cell migration, and inactivation of this gene by mutation is associated with the development of multiple malignant tumors [ 10 ]. (alliedacademies.org)
  • The most frequent mutation of B-RAF is the valine-to-glutamic acid substitution at codon 600 (V600E), which has been observed in several cancers [ 1 ]. (hindawi.com)
  • It is widely accepted that TGF-β is a tumor suppressor, given the frequent occurrence of many types of tumors in mice with disruptions of TGF-β signaling components by gene targeting and many types of human cancers containing loss-of-function mutation of TGF-β signaling components [ 4 ]. (biomedcentral.com)
  • Raf-1 is a protein encoded by the RAF1 gene which is approximately 73 kDa. (stjohnslabs.com)
  • Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. (stjohnslabs.com)
  • Nuclear Factor kappa-light-chain-enhancer of activated B cells or NF-κB is a protein complex that controls the transcription of DNA. (rockland-inc.com)
  • The mammalian nuclear factor-κB (NF-κB) family contains five proteins, RelA/p65, NF-κB1 (p50), NF-κB2 (p52), c-Rel, and RelB, which can form a variety of homodimers and heterodimers to differently control gene expression. (aacrjournals.org)
  • The inappropriate retention of intron 4 during processing of cyclin D1 transcripts results in production of a variant protein termed cyclin D1b that serves as a nuclear oncogene ( 3 ), whereas expression of CD44 isoforms containing variable exon 6 increases metastatic propensity of pancreatic carcinoma cells ( 4 , 5 ). (aacrjournals.org)
  • Identification of nucleolar protein NOM1 as a novel nuclear IGF1R-interacting protein. (abcam.com)
  • The Myc proteins are short-lived nuclear transcription factors that regulate cell growth and apoptosis ( 1 ). (aacrjournals.org)
  • Menin, the product of the MEN1 gene, is a nuclear protein. (springer.com)
  • Bach1 competes with nuclear factor (erythroid-derived 2)-like-2 (Nrf2) for binding to the MAREs in oxidative stress-response genes. (hindawi.com)
  • Under normal physiological conditions, nuclear Nrf2 contributes to vascular protection by inducing expression of the glutamate cysteine ligase modulatory subunit (GCLM) and the light chain component of system x c − (xCT) in human endothelial cells, while cytoplasmic Nrf2 is bound and inhibited by Kelch-like ECH-associated protein 1 (Keap1) [ 15 ]. (hindawi.com)
  • Even though a small protein such as p8 would not need a nuclear localization signal (NLS) to be transported to the nucleus, a clear NLS can be predicted for the eleven proteins comprising a bipartite domain of positively charged aminoacids. (biomedcentral.com)
  • PML nuclear bodies (NBs) are dynamic intranuclear structures harboring numerous transiently or permanently localized proteins. (asm.org)
  • PML is the NBs' organizer ( 20 , 26 ), since in acute promyelocytic leukemia and in PML knockout −/− cells, PML NBs do not exist, and proteins normally recruited to these structures are no longer NB-associated and present a diffuse nuclear localization outside the NBs. (asm.org)
  • Nuclear matrix-targeting of PML was shown, however, to occur independently of SUMOylation ( 23 ), even though this modification of PML is important for formation of NBs and the recruitment of specific proteins to these structures ( 20 , 25 ). (asm.org)
  • We noted abnormal apoptotic cell death in the domain of slik and GFP expression, even when the larvae were raised at 18°C. Cellular and nuclear morphology were normal within the plane of the epithelium, but pyknotic nuclei were visible in GFP-expressing cells extruded below the epithelium (Figure 7A and 7B). (nih.gov)
  • Apoptosis was first described by its morphological characteristics, including cell shrinkage, plasma membrane disruption, chromatin condensation, and nuclear DNA cleavage into discrete fragments (1-3). (isciii.es)
  • However, nuclear remnants from cells having undergone apoptosis exhibit an alternating band pattern -in the shape of ladder rungs- known as the ladder pattern that is an unmistakable sign that the death process studied was apoptotic in nature. (isciii.es)
  • IAV modulate the activity of several cellular signaling cascades, which are in part exploited by the virus to enable efficient replication. (frontiersin.org)
  • We have identified 135 genes in 1137 abstracts that either modulate the levels of homocysteine or are modulated by elevated levels of homocysteine. (biomedcentral.com)
  • Cellular acidosis triggers human MondoA transcriptional activity by driving mitochondrial ATP production. (abcam.com)
  • Loss of active Ras and of MycN in LAN-1 cells was manifested in profiles of gene expression that could be expected from the loss of MycN transcriptional activity and of Ras signaling. (aacrjournals.org)
  • The transcription factor BTB and CNC homology 1 (Bach1) is widely expressed in most mammalian tissues and functions primarily as a transcriptional suppressor by heterodimerizing with small Maf proteins and binding to Maf recognition elements in the promoters of targeted genes. (hindawi.com)
  • Our lab is also studying the role of prohibitin, a potential tumor suppressor protein that interacts with Rb and represses E2F transcriptional activity. (moffitt.org)
  • a-raf, b-raf, and c-raf for the murine proteins and A-Raf, B-Raf, and C-Raf for the corresponding genes. (atlasgeneticsoncology.org)
  • Here we report the cloning, sequencing, and structural organization of the mouse p110delta gene from a murine 129/Sv genomic library. (embl.de)
  • NF-κB proteins are normally sequestered in the cytoplasm through interactions with IκB family of proteins ( 1 ). (aacrjournals.org)
  • GSH has diverse cellular functions in addition to its antioxidant properties including enzymatic conjugation through the glutathione S -transferase family of proteins and nonenzymatic conjugation to cytotoxic compounds. (aspetjournals.org)
  • Since their discovery almost 20 years ago, the Inhibitor of Apoptosis (IAP) family of proteins have gathered growing interest as possible drug targets in a wide range of malignancies. (omicsonline.org)
  • However, the mechanisms of senile apoptosis differ from the mechanisms of cell death in the early stages of ontogenesis. (intechopen.com)
  • Activated monocytes and macrophages produce a range of cytotoxins, interferons and interleukins, which participate in the defense mechanisms of body, as well as growth factors that promoting the growth of endothelial cells and smooth muscle cell [ 8 , 9 ]. (alliedacademies.org)
  • In the following review we highlight several distinct mechanisms of translation control and provide specific examples of translational control during apoptosis. (exp-oncology.com.ua)
  • They achieve this by a number of mechanisms, including direct lysis, apoptosis, expression of toxic proteins, autophagy and shut-down of protein synthesis, as well as the induction of anti-tumoral immunity. (mdpi.com)
  • Homocysteine-induced modulation of gene expression through alteration of methylation status or by hitherto unknown mechanisms is predicted to lead to several pathological conditions either directly or indirectly. (biomedcentral.com)
  • Many natural products promoted as having anti-cancer and anti-inflammatory activity have been shown to inhibit NF-κB. (rockland-inc.com)
  • Gastrin's actions are mediated through the Gastric cancer is histologically classified into diffuse and G-protein-coupled receptor cholecystokinin-B (CCK-B) intestinal types, termed PGC (poorly-differentiated GC) on parietal and enterochromaffin cells of the gastric and WGC (well-differentiated GC), respectively [1-4]. (deepdyve.com)
  • Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells. (labome.org)
  • We suggest that RKIP may serve as an immune surveillance cancer gene, and its low expression or absence in tumors allows the tumor to escape host immune cytotoxic effector cells. (labome.org)
  • We have generated a lung cancer mouse model by targeting constitutively active C-Raf kinase to the lung. (biomedcentral.com)
  • This states that only one working allele of a tumour suppressor gene is necessary for its function (the mutated gene is recessive), and so both need to be mutated before the cancer phenotype will appear. (wikipedia.org)
  • PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. (aacrjournals.org)
  • We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. (aacrjournals.org)
  • PIK3CA , which encodes alpha isoform of the class I PI3K catalytic subunit, is one of the most commonly altered oncogenes in human cancer ( 4 ). (aacrjournals.org)
  • Mutant, constitutively activated forms of Ras proteins are frequently found in cancer. (embl.de)
  • p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells. (biomedcentral.com)
  • Tan-IIA could inhibit human gastric cancer SGC7901 cells and MKN-45 cells time- and dose-dependently through inducing apoptosis and cell cycle phase arrest ( 19 - 21 ). (spandidos-publications.com)
  • Clinical relevance of gene expression in localized and metastatic prostate cancer exemplified by FABP5. (dkfz.de)
  • Special attention will be given to the expression of the let-7 family of miRNAs - measured by Northern blotting and quantitative RT-PCR - in non-small cell lung cancer samples and corresponding normal lung tissues in relation to expression of the RAS oncogene. (libpubmedia.co.uk)
  • Dr. John Cleveland was trained at the National Cancer Institute under the direction of Dr. Ulf R. Rapp (who discovered Raf family oncogenes) and began his career as an Assistant Professor in the Department of Biochemistry of St. Jude Children's Research Hospital in 1989. (moffitt.org)
  • The mechanistic target of rapamycin (mTOR) protein kinase coordinates responses to nutrients and growth factors and is an anti-cancer drug target. (biologists.org)
  • In vertebrate cells, the elimination of DSBs with minimal nucleotide sequence change involves the spatiotemporal orchestration of an apparently endless number of proteins ranging, according to their action, from the nucleotide level to nucleosome organization and chromosome architecture. (wikipathways.org)
  • In mammalian cells, the formation of DSBs initiates a massive global cellular response, either checkpoint signaling and repair or cell death (apoptosis). (wikipathways.org)
  • 2 Subsequent immunophenotyping and gene rearrangement studies showed that the vast majority of ALCL tumors are derived from lymphoid cells of T or null immunophenotype. (bloodjournal.org)
  • Transforming growth factor-β (TGF-β) elicits distinct cellular response patterns of epithelial cells in a highly context-dependent manner ( 1 ). (pnas.org)
  • By establishing PP2A as a key player in the response of cells to growth factors and stress signals like TNF‐α, our findings could explain why PP2A is a primary target utilized during SV40 infection to alter cellular behavior. (embopress.org)
  • We are particularly interested in the role of longevity genes in the maintenance of the pool of adult neural stem cells and intact cognitive function during aging. (stanford.edu)
  • De novo FA synthesis is very active during embryogenesis, whereas most adult normal cells and tissues, even those with high cellular turnover, preferentially use circulating FA for the synthesis of new structural and signaling lipids. (aacrjournals.org)
  • Human neuroblastoma LAN-1 cells, in which the MycN gene is amplified, were used to examine the impact of the Ras inhibitor farnesylthiosalicylic acid on cell growth, on the levels Ras and MycN proteins, and on profiles of gene expression. (aacrjournals.org)
  • c) BCR-ABL phosphorylates STAT5 which also aid in evading apoptosis of CML cells. (hindawi.com)
  • Some of these studies will include an evaluation of how cells control the way that genes are expressed, how cells 'know' to become retinal cells, how cells remain retinal cells, how cells lose their identity as retinal cells, what changes make retinoblastoma cells different from normal retinal cells, and what changes make some retinoblastomas worse than others. (stanford.edu)
  • Another transcription factor in the basic region leucine zipper family, Bach2, is expressed in B cells, T cells, macrophages, and neural cells [ 4 ] and is involved in oxidative stress-mediated apoptosis, macrophage-mediated innate immunity, and adaptive immune response [ 5 - 7 ]. (hindawi.com)
  • It is primarily a neuronal protein, but can also be found in the neuroglial cells. (biolegend.com)
  • More than 60% of intracellular proteins from GBM CD133 + CSCs are identical to proteins present in normal neural stem cells of a human brain ( 11 ). (spandidos-publications.com)
  • Further experiments have shown that p8 mRNA is activated in almost all cells in response to several stresses [ 2 ], including minimal stresses such as after routine change of the culture medium in the absence of any added substance [ 3 ], indicating that p8 is a ubiquitous protein induced by cellular stress. (biomedcentral.com)
  • In the present study, we investigated the protein expression levels of PI3K, AKT and mTOR in AGS cells treated with Tan-IIA both in vitro and in vivo. (spandidos-publications.com)
  • Like dendritic cells, Dictyostelium amoebae are active in macropinocytosis, and various proteins have been identified that contribute to this process. (embl.de)
  • To investigate the possible role(s) of mammalian Vps34p in protein targeting to lysosomes, we have cloned the rat orthologue and overexpressed a kinase-deficient mutant in HeLa cells. (embl.de)
  • As a result, the expression of CCND1 and MCL1, proteins encoded by eIF4E-sensitive and cap-dependent transcripts, was refractory to AZD8055 in SW620:8055R cells. (biologists.org)
  • Cells possess two discrete multi-protein mTOR complexes, mTORC1 and mTORC2. (biologists.org)
  • One of the key advantages of translational control is the ability of cells to rapidly reprogram the protein output in response to internal or external triggers. (exp-oncology.com.ua)
  • This was examined in more detail in imaginal discs using green fluorescent protein (GFP) to mark cells overexpressing slik. (nih.gov)
  • Activated Ras causes a dramatic increase in the number of circulating larval hemocytes (blood cells), which is caused by cellular overproliferation. (genetics.org)
  • The four Notch genes identified in mammals ( Notch 1-4 ) are expressed in a wide variety of cells and play a significant role in cellular differentiation. (iiarjournals.org)
  • In contrast to apoptosis, where cells play an active role in their own destruction, in necrosis cells undergo lysis by cytokines produced by inflammatory cells. (isciii.es)
  • Nitrogen Cavitation and Differential Centrifugation Allows for Monitoring the Distribution of Peripheral Membrane Proteins in Cultured Cells Mo Zhou 1 , Mark R. Philips 1 1 Langone Medical Center, New York University Here we present protocols for detergent-free homogenization of cultured mammalian cells based on nitrogen cavitation and subsequent separation of cytosolic and membrane-bound proteins by ultracentrifugation. (jove.com)
  • Ahnert-Hilger G, Schafer T, Spicher K, Grund C, Schultz G, Wiedenmann B (1994) Detection of G-protein heterotrimers on large dense core and small synaptic vesicles of neuroendocrine and neuronal cells. (springer.com)
  • The levels of PTEN mRNA expression in these samples were examined by quantitative Real-time PCR, while PTEN protein levels were analysed by Western Blot and ELISA. (alliedacademies.org)
  • We investigated the expression of PTEN mRNA and protein by Real-time PCR, Western blot and ELISA in Alveolar Macrophages (AMs), serum and peripheral blood monocytes from patients with VAP. (alliedacademies.org)
  • Here we explored the anti-IAV action of the licensed B-Raf V600E inhibitor Vemurafenib. (frontiersin.org)
  • CDKN2A encodes two distinct tumor suppressor proteins in alternative reading frames: the CDK inhibitor p16/INK4a and the p53 activator p14/ARF. (aacrjournals.org)
  • One of the open reading frames of the HBV genome encodes a protein termed HBx. (biomedcentral.com)
  • The shorter, major isoform - consisting of 17 exons - encodes a protein kinase of 648 amino acids. (wikipedia.org)
  • The binding proteins increase the half life of IGF, preventing renal clearance and inactivation. (atlasgeneticsoncology.org)
  • Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type β signaling. (springer.com)
  • The elucidation of the genomic structure of the catalytic subunits is a necessary step for the investigation of the function of PI3K isoforms by inactivation of the gene in vivo. (embl.de)
  • intense fluorescence is maintained in complex cellular environments and under various biological conditions including changes in intracellular pH, temperature, and metabolic activity. (thermofisher.com)
  • SMAD7 interaction leads to the ubiquitination and degradation of the receptors with the help SMAD specific E3 ubiquitin protein ligase ( SMURF ). (bio-rad.com)
  • Heterotrimeric G-proteins are key transducers for signal transfer from outside the cell, mediating signals emanating from cell-surface G-protein coupled receptors (GPCR). (springer.com)
  • AGS proteins) refer to a functionally defined group of proteins that activate selected G-protein signaling systems in the absence of classical G-protein coupled receptors. (springer.com)
  • Identifying these tumors with this translocation became clinically feasible after the production of antibodies that specifically interact with chimeric NPM-ALK and full-length ALK proteins. (bloodjournal.org)
  • We have previously established this mouse model by expressing mutated, constitutively active C-Raf kinase (C-Raf BxB) under the control of the human surfactant protein C (SP-C) promoter [ 10 ]. (biomedcentral.com)
  • Examples of well validated 14-3-3 interaction partners are the proto-oncogene RAF-1 ( 7 - 9 ) and the cell-cycle regulatory phosphatases Cdc25C/B ( 10 , 11 ). (pnas.org)
  • C-Raf BxB lacks the regulatory NH 2 -terminal sequences including the Ras interaction domain. (biomedcentral.com)
  • The interaction between miRNAs and specific oncogenes and cell cycle regulatory genes is not well understood. (libpubmedia.co.uk)
  • NF-κB proteins were initially identified as pivotal transcription factors in chronic inflammatory diseases ( 2 ). (aacrjournals.org)
  • When phosphorylated, pRb releases its suppression of E2F transcription factors, which can then induce transcription of S phase-specific genes and thus facilitate the G 1 -to-S transition. (asm.org)
  • Then the AHR/ARNT heterodimer enhances the expression of its target genes that encode drug-metabolizing cytochrome P450s, including CYP1A1, CYP1A2 , and CYP1B1 ( 6 ) ( Figure 1 ). (frontiersin.org)
  • The IAPs were first discovered in baculoviruses, where they were found to encode for proteins (cpIAP, OpIAP) able to inhibit apoptosis in the host cell [ 1 , 2 ]. (omicsonline.org)
  • The BCL-2 family controls the integrity of the outer mitochondrial membrane (OMM) and is functionally divided into anti- and pro-apoptotic proteins. (biomedcentral.com)
  • 2004). Acute ablation of survivin uncovers p53-dependent mitotic checkpoint functions and control of mitochondrial apoptosis. (core.ac.uk)
  • Cyclin D/Cdk4 complexes phosphorylate the retinoblastoma gene product (pRb) early in the G 1 phase of the cell cycle, while cyclin E/Cdk2 complexes phosphorylate pRb in late G 1 . (asm.org)
  • Cyclin/Cdk complexes are regulated by a group of proteins known as Cdk inhibitors (CKIs). (asm.org)
  • Oncogene-based therapeutics is a novel approach to inhibit proteins, which are essential for the initiation and maintenance of malignancies [ 1 ]. (biomedcentral.com)
  • Once formed, the Bach1-Maf heterodimers inhibit the transcription of many oxidative stress-response genes, including heme oxygenase-1 (HO-1) [ 2 ] and NADPH quinone oxidoreductase 1(NQO1) [ 3 ], by binding to Maf recognition elements (MAREs) in the gene promoters. (hindawi.com)
  • Control of ASPP2/53BP2L protein levels by proteasomal degradation modulates p53 apoptotic function. (ohsu.edu)
  • BCL-2/BCL-xL/MCL-1) preserve OMM integrity by directly sequestering the pro-apoptotic proteins, which cooperate to form pores with the OMM. (biomedcentral.com)
  • While apoptosis is a programmed cell death, not all programmed deaths are apoptotic. (isciii.es)
  • Serre L, Pereira de Jesus K, Zelwer C, Bureaud N, Schoentgen F, Benedetti H. Crystal structures of YBHB and YBCL from Escherichia coli, two bacterial homologues to a Raf kinase inhibitor protein. (labome.org)
  • In this study the effect of the Raf kinase inhibitor BAY 43-9006 and of the MEK inhibitor CI-1040 (PD184352) on a Raf dependent lung tumor mouse model was analyzed in detail. (biomedcentral.com)
  • Hsp90 is the major mammalian protein and is required by BCR-ABL for stabilization and maturation. (hindawi.com)
  • However, biochemical properties of the mammalian p8 proteins are shared by some high mobility group proteins (HMG) [ 7 ], particularly by the HMG-I/Y family. (biomedcentral.com)
  • Ras oncogene at 64B ( Ras64B , also known as Ras2 ) is the Drosophila counterpart of mammalian R-ras . (genetics.org)
  • 1998). AIM-1: a mammalian midbody-associated protein required for cytokinesis. (core.ac.uk)
  • Berman DM, Gilman AG (1998) Mammalian RGS proteins: barbarians at the gate. (springer.com)