Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.Cyclin A: A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.Epstein-Barr Virus Nuclear Antigens: Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.Cyclin E: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Cyclin B: A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.Replication Protein C: A DNA-binding protein that consists of 5 polypeptides and plays an essential role in DNA REPLICATION in eukaryotes. It binds DNA PRIMER-template junctions and recruits PROLIFERATING CELL NUCLEAR ANTIGEN and DNA POLYMERASES to the site of DNA synthesis.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Cyclin D2: A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.Cyclin D3: A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.Cyclin A1: A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Cyclin D: A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Antigens, Bacterial: Substances elaborated by bacteria that have antigenic activity.Cyclin A2: A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.DNA Replication: The process by which a DNA molecule is duplicated.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Antigens, Nuclear: Immunologically detectable substances found in the CELL NUCLEUS.DNA Polymerase III: A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms but may be present in higher organisms. Use also for a more complex form of DNA polymerase III designated as DNA polymerase III* or pol III* which is 15 times more active biologically than DNA polymerase I in the synthesis of DNA. This polymerase has both 3'-5' and 5'-3' exonuclease activities, is inhibited by sulfhydryl reagents, and has the same template-primer dependence as pol II. EC 22.214.171.124.Respiratory Aspiration of Gastric Contents: Inhaling refluxed gastric or duodenal contents.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cell Cycle: 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.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.4-Hydroxycoumarins: Substances found in many plants, containing the 4-hydroxycoumarin radical. They interfere with vitamin K and the blood clotting mechanism, are tightly protein-bound, inhibit mitochondrial and microsomal enzymes, and are used as oral anticoagulants.Cyclin G1: A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.Cyclin G: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Herpesvirus 4, Human: The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.Cell Cycle Proteins: 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.Cyclin C: A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cyclin-Dependent Kinase Inhibitor p21: 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.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.DNA-Directed DNA Polymerase: DNA-dependent DNA polymerases found in bacteria, animal and plant cells. During the replication process, these enzymes catalyze the addition of deoxyribonucleotide residues to the end of a DNA strand in the presence of DNA as template-primer. They also possess exonuclease activity and therefore function in DNA repair.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Flap Endonucleases: Endonucleases that remove 5' DNA sequences from a DNA structure called a DNA flap. The DNA flap structure occurs in double-stranded DNA containing a single-stranded break where the 5' portion of the downstream strand is too long and overlaps the 3' end of the upstream strand. Flap endonucleases cleave the downstream strand of the overlap flap structure precisely after the first base-paired nucleotide, creating a ligatable nick.Ki-67 Antigen: A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.DNA: 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).Antigens, Polyomavirus Transforming: Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.DNA-Binding Proteins: 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.Cyclin B2: A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.Cell Nucleus: 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)Protein Binding: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Cyclin-Dependent Kinase 4: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.Antigens, Protozoan: Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.Cyclin T: A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.Apoptosis: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.G1 Phase: The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.Cells, Cultured: 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.DNA Damage: 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.HLA Antigens: Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.Blotting, Western: 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.Cyclin G2: An unusual cyclin subtype that is found highly expressed in terminally differentiated cells. Unlike conventional cyclins increased expression of cyclin G2 is believed to cause a withdrawal of cells from the CELL CYCLE.Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Cyclin H: A cyclin subtype that is found as a component of a heterotrimeric complex containing cyclin-dependent kinase 7 and CDK-activating kinase assembly factor. The complex plays a role in cellular proliferation by phosphorylating several CYCLIN DEPENDENT KINASES at specific regulatory threonine sites.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.RNA, Messenger: 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.HeLa Cells: 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.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Antigens, Fungal: Substances of fungal origin that have antigenic activity.Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.Tumor Suppressor Protein p53: 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.Antigens, Helminth: Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.H-2 Antigens: The major group of transplantation antigens in the mouse.Hyperplasia: An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.Tumor Cells, Cultured: 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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Cell Line, Tumor: A cell line derived from cultured tumor cells.Colonic Neoplasms: Tumors or cancer of the COLON.Transfection: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Antigens, Viral, Tumor: Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.Herpesvirus 8, Human: A species in the genus RHADINOVIRUS, subfamily GAMMAHERPESVIRINAE, isolated from patients with AIDS-related and "classical" Kaposi sarcoma.Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.Epitopes: Sites on an antigen that interact with specific antibodies.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Promoter Regions, Genetic: 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.Ubiquitination: The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Flow Cytometry: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Recombinant Fusion Proteins: 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.Gene Expression Regulation: 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.Immunoblotting: 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.HLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.Mitotic Index: An expression of the number of mitoses found in a stated number of cells.Liver Regeneration: Repair or renewal of hepatic tissue.Oncogene Proteins: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).DNA Polymerase II: A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. EC 126.96.36.199.Pyrococcus furiosus: A species of strictly anaerobic, hyperthermophilic archaea which lives in geothermally-heated marine sediments. It exhibits heterotropic growth by fermentation or sulfur respiration.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.Mice, Inbred BALB CDNA Primers: 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.DNA Ligases: Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 188.8.131.52 (ATP) and EC 184.108.40.206 (NAD).Receptors, Antigen, T-Cell: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.G2 Phase: The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.T-Lymphocytes: 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.In Situ Nick-End Labeling: 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.Burkitt Lymphoma: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.Mice, Inbred C57BLHistocompatibility Antigens: A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.Proto-Oncogene Proteins c-bcl-2: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Rats, Sprague-Dawley: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Antibodies, Antinuclear: Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Receptors, Antigen, B-Cell: IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.Tumor Markers, Biological: Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.Prostate-Specific Antigen: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Histocompatibility Antigens Class II: Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Precipitin Tests: Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.O Antigens: The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.DNA Polymerase beta: A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC 220.127.116.11.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Neoplasm Proteins: 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.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Signal Transduction: 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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Cyclin I: A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.Disease Models, Animal: 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.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Ubiquitin-Conjugating Enzymes: A class of enzymes that form a thioester bond to UBIQUITIN with the assistance of UBIQUITIN-ACTIVATING ENZYMES. They transfer ubiquitin to the LYSINE of a substrate protein with the assistance of UBIQUITIN-PROTEIN LIGASES.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Down-Regulation: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Antigens, CD15: A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.Cell Transformation, Neoplastic: 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.Tumor Suppressor Proteins: 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.Antigens, Tumor-Associated, Carbohydrate: Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.HLA-A2 Antigen: A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.G0 Phase: A quiescent state of cells during G1 PHASE.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Antigens, CD8: Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.HLA-A Antigens: Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Epithelial Cells: 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.Proto-Oncogene Proteins: 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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Kinetics: The rate dynamics in chemical or physical systems.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.E2F Transcription Factors: A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Antigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Blood Group Antigens: Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.Hepatitis B Surface Antigens: Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Up-Regulation: 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.Mice, Nude: 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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Simian virus 40: A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.Antigen-Antibody Reactions: The processes triggered by interactions of ANTIBODIES with their ANTIGENS.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Histocompatibility Antigens Class I: Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.Chromatin Assembly Factor-1: A histone chaperone protein that plays a role in the deposition of NUCLEOSOMES on newly synthesized DNA. It is comprised of three different subunits of 48, 60, and 150 kDa molecular size. The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling.Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called PRIONS.Cell Line, Transformed: 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.Models, Biological: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Scenedesmus: A genus of GREEN ALGAE in the family Scenedesmaceae. It forms colonies of usually four or eight cylindrical cells that are widely distributed in freshwater and SOIL.Genes, bcl-1: The B-cell leukemia/lymphoma-1 genes, associated with various neoplasms when overexpressed. Overexpression results from the t(11;14) translocation, which is characteristic of mantle zone-derived B-cell lymphomas. The human c-bcl-1 gene is located at 11q13 on the long arm of chromosome 11.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Immunoglobulin J Recombination Signal Sequence-Binding Protein: A ubiquitously expressed sequence-specific transcriptional repressor that is normally the target of signaling by NOTCH PROTEINS.RNA, Small Interfering: 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.Viral Proteins: Proteins found in any species of virus.Rats, Inbred F344Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
"A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. ... PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein ... "A proteomics approach to identify proliferating cell nuclear antigen ( ... Cyclin-O is a protein that in humans is encoded by the CCNO gene. Cyclin O has been shown to interact with RPA2 and PCNA. ...
"Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin". EMBO J. 6 (3): 637-42. PMC 553445 ... "p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex". ... "Association of proliferating cell nuclear antigen with cyclin-dependent kinases and cyclins in normal and transformed human T ... "Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication through a conserved p21(Cip1)-like PCNA- ...
... and a molecule called proliferating cell nuclear antigen, or PCNA, which speeds DNA replication and repair by helping to attach ... When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases (CDK) and cyclins phosphorylate Rb to pRb, ... When E2F is free it activates factors like cyclins (e.g. cyclin E and cyclin A), which push the cell through the cell cycle by ... For example, Rb was detected on the cyclin A and PCNA promoters in senescent cells. Cells in response to stress in the form of ...
"The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA- ... "p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex". ... PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21". J. Biol. ... "p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex". ...
... interacts with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in ... is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily ... of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen ... "Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor ...
A bypass platform is provided to these polymerases by Proliferating cell nuclear antigen (PCNA). Under normal circumstances, ... and can arrest the cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The ... proliferating cell nuclear antigen (PCNA)-like group, two serine/threonine(S/T) kinases and their adaptors. Central to all DNA ... After DNA damage, cell cycle checkpoints are activated. Checkpoint activation pauses the cell cycle and gives the cell time to ...
... of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen ... complexed with human PCNA. „Cell". 87 (2), s. 297-306, 1996. PMID: 8861913. ... proliferating cell nuclear antigen − PCNA), czynnikiem dodatkowym polimerazy DNA, i tym samym odgrywać rolę regulatora zarówno ... Human proliferating cell nuclear antigen, poly(ADP-ribose) polymerase-1, and p21waf1/cip1. A dynamic exchange of partners. „J. ...
"Structural and biochemical studies of human proliferating cell nuclear antigen complexes provide a rationale for cyclin ... complexed with human PCNA". Cell. 87 (2): 297-306. doi:10.1016/S0092-8674(00)81347-1. PMID 8861913. Suzuka I, Hata S, Matsuoka ... Proliferating cell nuclear antigen from Pyrococcus furiosus". Protein Sci. 10 (1): 17-23. doi:10.1110/ps.36401. PMC 2249843 . ... "Highly conserved structure of proliferating cell nuclear antigen (DNA polymerase delta auxiliary protein) gene in plants". Eur ...
... the sliding clamp is a homotrimer ring structure known as the proliferating cell nuclear antigen (PCNA). The PCNA ring has ... Zou L, Stillman B (April 1998). "Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto ... and proliferating cell nuclear antigen (PCNA) onto chromatin. Within a Xenopus nucleus-free system, it has been demonstrated ... Yao NY, Johnson A, Bowman GD, Kuriyan J, O'Donnell M (June 2006). "Mechanism of proliferating cell nuclear antigen clamp ...
Ki-67 and proliferating cell nuclear antigen (PCNA), are regulated by these factors. Additionally, PCNA has been suggested to ... P27 inhibits cell cycle progression at the G1 phase by preventing the action of cyclin E-Cdk2. Due to its' important role in ... The TSC complex also plays an important role in this pathways by suppressing the activity of mTOR which has been proven to be ... Communication between the oocytes and the surrounding somatic cells, such as the granulosa cells and the theca cells, is ...
Proliferating cell nuclear antigen (PCNA) is a protein involved in DNA synthesis. Under normal physiological conditions PCNA is ... When cyclin E is partnered with CDK2 and get phosphorylated, an SCF-associated F-box protein Fbw7 recognizes the complex and ... The anaphase-promoting complex (APC) and the SCF complex (for Skp1-Cullin-F-box protein complex) are two examples of multi- ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. This is achieved by ...
... has been shown to possibly regulate the interaction between the RFTS to the proliferating cell nuclear antigen (PCNA) when ... "Cell cycle-dependent phosphorylation of human DNA ligase I at the cyclin-dependent kinase sites". J. Biol. Chem. 278 (39): ... "Long patch base excision repair proceeds via coordinated stimulation of the multienzyme DNA repair complex". J. Biol. Chem. 284 ... 1999). "Reconstitution of proliferating cell nuclear antigen-dependent repair of apurinic/apyrimidinic sites with purified ...
Hu J, Xiong Y (Feb 2006). "An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by ... Both CRL4 complexes utilize Cdt2 and the DNA processivity factor PCNA to induce the ubiquitination and degradation of ... "Involvement of CUL4 ubiquitin E3 ligases in regulating CDK inhibitors Dacapo/p27Kip1 and cyclin E degradation". Cell Cycle. 5 ( ... "CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV ...
... has shown to mediate DNA repair mechanisms and does so by activating repair factors such as proliferating cell nuclear antigen ... The degradation has an inhibitory effect on the formation of cyclin-dependent kinase complexes, which are key drivers of the ... PCNA), FANCE, Rad51 and TLK. Chk1 facilitates replication fork stabilization during DNA replication and repair however more ... cell cycle arrest, DNA repair and cell death to prevent damaged cells from progressing through the cell cycle. In 1993, Beach ...
... and a molecule called proliferating cell nuclear antigen, or PCNA, which speeds DNA replication and repair by helping to attach ... See also: cyclin-dependent kinase and DREAM complex. When it is time for a cell to enter S phase, complexes of cyclin-dependent ... cyclin/CDK positive transcription elongation factor complex. • chromatin. • cell nucleus. • nucleoplasm. • Rb-E2F complex. ... When E2F is free it activates factors like cyclins (e.g. cyclin E and cyclin A), which push the cell through the cell cycle by ...
... of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen ... It encodes a cell cycle inhibitor that binds to G1 cyclin-CDK complexes. Thus p57KIP2 causes arrest of the cell cycle in G1 ... Cyclin-dependent kinase inhibitor 1C has been shown to interact with: LIMK1, MYBL2, MyoD, and PCNA. ENSG00000129757 GRCh38: ... of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell nuclear antigen ...
... with proliferating cell nuclear antigen impedes negative growth control". J. Biol. Chem. 276 (4): 2766-74. doi:10.1074/jbc. ... This gene plays a role in cell cycle regulation. GADD45G prevents the kinase ability of the cyclin b1/Cdk1 complex in a fashion ... The central region contains a highly acidic patch where it allows for interaction with cdc2, PCNA, and p21. The parallel ... It also interacts with CRIF, which causes the inhibition of Cdc2-cyclin B1 and Cdk-cyclin E. GADD45 also works with the cyclin- ...
Hu J, Xiong Y (Feb 2006). "An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by ... complexes during S phase and following DNA damage in a PCNA-dependent manner. CRL4A complexes regulate entry into the DNA ... Interestingly, both substrates are also regulated by the SCFSkp2 complex. CRL4-mediated destruction of p21 relieves cyclin E- ... "CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV ...
Milutinovic S, Zhuang Q, Szyf M (June 2002). "Proliferating cell nuclear antigen associates with histone deacetylase activity, ... "A novel nuclear receptor corepressor complex, N-CoR, contains components of the mammalian SWI/SNF complex and the corepressor ... and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression" (PDF ... Nuclear receptor co-repressor 2, PCNA, PHF21A, Prohibitin, Promyelocytic leukemia protein, RAD9A, RBBP4, RBBP7, RCOR1, RELA, ...
Matsuoka S, Yamaguchi M, Matsukage A (April 1994). "D-type cyclin-binding regions of proliferating cell nuclear antigen". J. ... This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell ... PCNA, PPARG, RAD51, RB1, TAF1, and NR1A2. Parathyroid adenoma Mantle Cell Lymphoma GRCh38: Ensembl release 89: ENSG00000110092 ... Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G (May 1993). "Cyclin D1 is a nuclear protein required for cell cycle ...
... modulates proliferating cell nuclear antigen binding.. J. Biol. Chem. 275: 11529 - 11537. PubMed DOI:10.1074/jbc.275.15.11529 ... cyclin-dependent protein kinase holoenzyme complex. • PCNA-p21 complex. • perinuclear region of cytoplasm. • клітинне ядро. • ... G2/M transition of mitotic cell cycle. • positive regulation of B cell proliferation. • negative regulation of cell growth. • ... cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ...
Structural and biochemical studies of human PCNA complexes provide the basis for association with CDK/cyclin and rationale for ... complexes and with proliferating cell nuclear antigen (PCNA) regulate and coordinate the processes of cell-cycle progression ... complexes and with proliferating cell nuclear antigen (PCNA) regulate and coordinate the processes of cell-cycle progression ... Structural and Biochemical Studies of Human Proliferating Cell Nuclear Antigen Complexes Provide a Rationale for Cyclin ...
... origin recognition complex; PCNA, proliferating cell nuclear antigen; preRC, prereplication complex; siRNA, small interfering ... we analyzed the localization patterns of BrdU and proliferating cell nuclear antigen (PCNA) in individual early S phase cells ... Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a ... Replication sites as revealed by double label immunofluorescence against proliferating cell nuclear antigen (PCNA) and ...
"A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. ... PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein ... "A proteomics approach to identify proliferating cell nuclear antigen ( ... Cyclin-O is a protein that in humans is encoded by the CCNO gene. Cyclin O has been shown to interact with RPA2 and PCNA. ...
... inhibitors is its ability to associate with the proliferating cell nuclear antigen (PCNA), an auxiliary fa... ... A unique feature of p21 that distinguishes it from the other cyclin-dependent kinase (CDK) ... While it is now well established that inhibition of cyclin/CDK complexes by p21 can result in G1 cell cycle arrest, the ... inhibitors is its ability to associate with the proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA ...
Structural and Biochemical Studies of Human Proliferating Cell Nuclear Antigen Complexes Provide a Rationale for Cyclin ... complexes and with proliferating cell nuclear antigen (PCNA) regulate and coordinate the processes of cell-cycle progression ... complexes and with proliferating cell nuclear antigen (PCNA) regulate and coordinate the processes of cell-cycle progression ... The quaternary complex shows little direct interaction between PCNA and cyclin, giving p21 the role of an adaptor molecule. ...
PCNA, proliferating cell nuclear antigen; pRb, retinoblastoma protein. ... Keywords: ABC, avidin-biotin complex; cdk, cyclin-dependent kinase; DES; diethylstilbestrol; E2, 17β-estradiol; ER, estrogen ... suggesting that this cell cycle suppressor protein is functional. In addition, cyclin D1-, cdk2-, cdk4- and cyclin E-associated ... Levels of cyclin D1, cyclin E and retinoblastoma (pRb).... There is strong evidence that estrogens are involved in the etiology ...
... and anti-proliferating cell nuclear antigen (anti-PCNA). Construction of Akt 1 siRNA and Preparation of Poly(ester amine)/ ... including cyclin D, which, when complexed with CDK4, moves into the next cell cycle (63). Cyclin A and cyclin E, which paired ... cyclin D3, cyclin A, cyclin E, CDK4, CDK2, CDC2, and PCNA (Figures 5A-5D). The expression of PCNA, a marker of cell ... cell division cycle (CDC) 2, anti-cyclin-dependent kinase 2 (anti- CDK2), anti-CDK4, anti-cyclin A, anti-cyclin B1, anti-cyclin ...
"Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin". EMBO J. 6 (3): 637-42. PMC 553445 ... "p21Cip1/Waf1 disrupts the recruitment of human Fen1 by proliferating-cell nuclear antigen into the DNA replication complex". ... "Association of proliferating cell nuclear antigen with cyclin-dependent kinases and cyclins in normal and transformed human T ... "Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication through a conserved p21(Cip1)-like PCNA- ...
1993) Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol. Biol. Cell. 4:897 ... Both p21 and cyclin D interact with proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerases δ and ɛ ... Early senescent cells accumulate p21-PCNA-cyclin D1-Cdk complexes.In contrast to an earlier report that senescent HDF lack PCNA ... cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes (44, 50, 55). In quiescent young HDF, cyclin D1 and cyclin E are present in low ...
Gadd45 was found to bind to PCNA, a normal component of Cdk complexes and a protein involved in DNA replication and repair. ... Like another p53-regulated gene, p21WAF1/CIP1, whose product binds to cyclin-dependent kinases (Cdks) and proliferating cell ... Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen ... Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen ...
... proliferating cell nuclear antigen (PCNA), 1-phosphatidylinositol 3-kinase (PI3K), peptidylprolyl cis/trans isomerase, NIMA- ... complex 1″ (Raptor), p21 Ras (Ras), retinoblastoma 1 (RB1), Ras homolog enriched in brain (Rheb), (Src homology 2 domain ... cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (p14ARF), tumor protein p53 (p53, TP53), microtubule ... nuclear envelope 1 (SYNE1), spectrin repeat containing, nuclear envelope 2 (SYNE2), TGF beta (Tgfβ), thyroid hormone (T3), ...
ELP was modified by p21, a cell cycle inhibitory peptide, and the addition of Bac, a cell-penetrating peptide with nuclear ... In this study, p21-ELP-Bac and its control, ELP-p21, were used in cell proliferation studies using the pancreatic cancer cell ... The majority of chemotherapeutic agents used in clinics are highly toxic to both tumor cells and normal tissues due to the lack ... and tumor reduction capabilities of the polypeptide with and without a cell-penetrating peptide.Keywords: elastin-like ...
... proliferating cell nuclear antigen (PCNA; antibody: Abcam, ab2426), phospho-Akt-Ser473 (Cell Signaling, 9271), cyclin D1 (EMD ... Upon receiving appropriate growth signals, pRb is hyperphosphorylated by cyclin-dependent kinase (cdk) complexes such as cyclin ... promoter region contributes to serum-dependent up-regulation of the human proliferating cell nuclear antigen gene. FEBS Lett ... Cells positive for iNOS (cytokine-stimulated ANA-1 mouse macrophages), pRb/E2F1/p53/p19ARF/PCNA/cyclin D1 (HCT 116), and ...
... cyclin-dependent kinase (cdk) and proliferating cell nuclear antigen (PCNA). It functions as a potent inhibitor of cyclin- ... The p21/WAF1 protein exists within the nucleus as a complex with cyclin, ... WA1 is a mouse IgG1 monoclonal antibody derived from the fusion of SP2 mouse myeloma cells with splenocytes from a BALB/c mouse ... p21/WAF1, also known as cip1 and cyclin-dependent kinase interacting protein 1, is a 21kD protein that belongs to the CDI ...
... cyclin dependent kinases (CDKs), and proliferating cell nuclear antigen (PCNA) in normal cells but not transformed cells and ... The 21 kDa product of the WAF1 gene is found in a complex involving cyclins, ... Controls contained A2780 cells and DMSO without compound and blanks contained DMSO but no cells. MTT was dissolved at 5 mg/ml ... Cells were routinely kept as monolayer cultures at 37.degree. C. in a humidified 5% CO.sub.2 atmosphere. Cells were passaged ...
... proliferating cell nuclear antigen (PCNA), cyclin B1 . However, intracerebral injection of AAV-Tau in cyclinD2 deficient ... Microtubules ensure cell shape and constitute roads of transport, a feature prominent in neurons with the most complex ... The activated inflammatory cells secrete then factors that affect not only neurons but also other cells that constitute the ... while attempts to reenter the cell cycle is considered pathological and eventually result in cell death. In AD and other ...
... inhibits viability by decreasing levels of proliferating cell nuclear antigen (PCNA) and cyclin D with parallel increase in p21 ... Dissociation of the Sp1-CDK4 complex promotes caspase activation and cell death. In addition one work has identified artesunate ... In normal cells, cyclin-dependent kinases (CDK) are the proteins translating signals in order to push cell through the cell ... Nuclear factor of kappa light polypeptide gene enhancer in B cells. NOXA:. Proapoptotic protein, a member of the BH3-only Bcl-2 ...
... proliferating cell nuclear antigen (PCNA) complex production and increasing the P21CIPI. Rg5 inhibited the migration of MNK-45 ... Rg5 could generate cell cycle S phase arresting by decreasing the CyclinA1/cyclin-dependent kinase 2 (CDK2)/ ... RESULTS: The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was ... A cell viability test, cell cycle analysis, transwell assay, ELISA and immunoblotting were performed. RESULTS: The viabilities ...
... independently of cyclins and CDKs, thanks to the strong affinity binding to proliferating cell nuclear antigen (PCNA) [14-17], ... Cyclin B-CDK1 complex has a relatively low affinity for p21 when compared with the other cyclin-CDK complexes , and a low ... 18 - Prosperi E. The fellowship of the rings: distinct pools of proliferating cell nuclear antigen (PCNA) trimer at work. FASEB ... Mechanism of inhibition of proliferating cell nuclear antigen-dependent DNA synthesis by the cyclin-dependent kinase inhibitor ...
The Proliferating Cell Nuclear Antigen (PCNA) was initially found as a nuclear protein that was recognized by auto antibodies ... PCNA has been found forming a quaternary complex with cyclin D, Cdk and p21. The physiological meaning of this complex has not ... we have detected the formation of complexes between the homotrimer protein ring Proliferating Cell Nuclear Antigen, PCNA, and ... PCNA also associates to proteins functioning in cell cycle control, as D cyclins, cyclin dependent kinases (Cdks) and p21 [7, ...
Molecular Cell Research" on DeepDyve, the largest online rental service for scholarly research with thousands of academic ... "E3 ubiquitin ligase HECW2 targets PCNA and lamin B1, Biochimica et Biophysica Acta (BBA) - ... Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA ... Proliferating cell nuclear antigen is protected from degradation by forming a complex with MutT Homolog2 ...
PCNA codes proliferating cell nuclear antigen expressed exclusively in actively proliferating cells . E2F1-3 induces ... Cyclin A/Cdk2 complexes regulate activation of Cdk1 and Cdc25 phosphatases in human cells. Oncogene. 2004; 23:3361-3367. ... Popov B and Petrov N. pRb-E2F signaling in life of mesenchymal stem cells: Cell cycle, cell fate, and cell differentiation. ... Cell number and proliferation kinetics. Cell number was determined using a CASY cell counter and analyzer (Roche, Germany) at ...
... and it consists of the proliferating cell nuclear antigen (PCNA; MIM 176740), the multisubunit replication factor C (see MIM ... The DNA polymerase delta complex is involved in DNA replication and repair, ... Western Blot: DNA Polymerase delta, catalytic subunit Antibody [NBP2-16184] - Sample (30 ug of whole cell lysate) A: Hela 7. 5 ... 102579), and the 4 subunit polymerase complex: POLD1, POLD2 (MIM 600815), POLD3 (MIM 611415), and POLD4 (MIM 611525) (Liu and ...
Buy our Recombinant Human PCNA protein. Ab172197 is a full length protein produced in Escherichia coli and has been validated ... Pcna/cyclin. *PCNA_HUMAN. *PCNAR. *Polymerase delta accessory protein. *Proliferating cell nuclear antigen ... Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, ... Recombinant Human PCNA protein (ab172197) at 0.000300000014249235 µg. Lane 4 : HeLa cell lysate at 10 µg. Lane 5 : HeLa cell ...
We previously showed that the Proliferating Cell Nuclear Antigen (PCNA) is expressed in the rodent ovarian follicles at the ... PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent ... Granulosa CellProliferate Cell Nuclear AntigenCyclin Dependent Kinase InhibitorPrimordial FolliclePrimary Follicle ... Cyclin E forms complexes during this interval with CDK2. Cyclins and CDKs assemble into complexes with one another as cells ...
KinasesCdk2InhibitorsCIP1CDKsPhosphorylationBindsSubunitTumorInteractionRegulatorsDegradationMammalianInhibitProliferativeQuaternary complexExpressionFibroblastsEukaryoticApoptoticWAF1GenomicVitro and in vivoPathwaysPhosphorylateKnockdownGrowthRegulatoryTargetsProcessivityHistoneHighly conservedClampHomotrimerTranscription
- In addition, amounts of the phosphorylated forms of cyclin-dependent kinases (cdk) 2 and 4 were decreased, and both RNA and protein levels of p27 kip1 (p27), a cyclin-dependent kinase inhibitor, were markedly higher in early and frank renal tumors than in adjacent uninvolved renal tissue and kidneys of untreated, age-matched animals. (oup.com)
- Like another p53-regulated gene, p21WAF1/CIP1, whose product binds to cyclin-dependent kinases (Cdk's) and proliferating cell nuclear antigen (PCNA), GADD45 has been associated with growth suppression. (sciencemag.org)
- It functions as a potent inhibitor of cyclin-dependent kinases and plays a critical role in regulating cell growth and the cellular response to DNA damage. (lsbio.com)
- Cdks are a family of protein kinases whose function is to regulate the cell cycle and p21 is a regulator of cyclin Cdk kinases. (scielo.org.mx)
- Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
- The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
- The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. (wikipathways.org)
- Kinases represent one group of genes that regulate many important cell functions and can be modulated by small molecules, thus represent a promising group of enzymes to screen for potential therapeutic targets. (pubmedcentralcanada.ca)
- Protein kinases thus act as key biochemical switches that affect the physiology of cells. (pubmedcentralcanada.ca)
- The most prominent TP53 target involved in G1 arrest is the inhibitor of cyclin-dependent kinases CDKN1A (p21). (wikipathways.org)
- Methods: A sequential fractionation procedure was used to isolate murine intestinal epithelial cells relative to their position along the crypt-villus axis, and the levels of cyclins, cyclin-dependent kinases (cdks), and cdk inhibitors and of the complexes formed among them was determined by immunoprecipitation-immunoblotting and kinase assays. (elsevier.com)
- The master regulators, cyclin dependant kinases (CDKs), are the actual driving forces behind the progression of cell cycle in eukaryotic cells. (omicsonline.org)
- The activity level of these kinases is maintained and controlled by the periodic synthesis and degradation of positive regulators, cyclins, negative regulators, cyclin kinase inhibitors (CKIs) and other reversible phosphorylation events. (omicsonline.org)
- Basically, CDKs are serine/threonine kinases consisting of a catalytic subunit (CDK) and a regulatory subunit (Cyclin). (omicsonline.org)
- The cyclins and their catalytic partners, the cyclin-dependent kinases (Cdks), are instrumental in driving the cell cycle forward. (asm.org)
- Results showed the redox activation of MAP kinases down regulated the mRNA levels of AP-1 subunits in aqueous areca nut extract treated cells. (springer.com)
- The eukaryotic cell cycle is driven by the periodic activation and inactivation of cyclin-dependent kinases (Cdks) and assembly of pre-RCs can only occur during the low Cdk activity period from late mitosis through G1 phase, with inappropriate re-assembly suppressed during S, G2, and M phases. (biomedcentral.com)
- The eukaryotic cell cycle is driven by the periodic activation and inactivation of cyclin-dependent kinases (Cdks), pre-RC assembly only occurring in a window of time during the low Cdk period from late mitosis through G1 phase. (biomedcentral.com)
- Cyclin-dependent kinases (cdks) 1 and their specific regulators cyclins are the best described regulators monitoring the cell cycle progression. (mcponline.org)
- In primary cultures of neonatal ventricular fibroblasts (NVFs) transduced with a tafazzin short hairpin RNA adenovirus, tafazzin knockdown increased production of reactive oxygen species and activation of mitogen-activated protein kinases and induced protein and DNA synthesis via cell cycle regulators. (physiology.org)
- Woo and Poon, 2003 ), and it is likely that cyclin E-Cdk2 has a role in this context, consistent with deregulated expression of cyclin E accelerating the G1/S transition. (rupress.org)
- Binding of the elevated p27 protein to cyclin E, cdk2 and cdk4, however, was not impaired, suggesting that this cell cycle suppressor protein is functional. (oup.com)
- In addition, cyclin D1-, cdk2-, cdk4- and cyclin E-associated kinase activities were also lower in these estrogen-induced renal neoplasms than in untreated, age-matched kidneys. (oup.com)
- We show that the Cdk inhibitor p21 Sdi1,Cip1,Waf1 , which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. (asm.org)
- Phosphorylation of pRb during G 1 phase is carried out by cyclin D-Cdk4 and cyclin D-Cdk6 (cyclin D-Cdk4/6) and cyclin E-Cdk2 complexes ( 44 , 50 , 55 ). (asm.org)
- In contrast, we have shown previously that although serum-stimulated senescent HDF (IMR90) have abundant cyclin E-Cdk2 complexes, they lack cyclin E-associated kinase activity, a finding consistent with their failure to phosphorylate pRb ( 14 ). (asm.org)
- Regulation of Cdk2 activity by activating (Thr-160) and inhibiting phosphorylations (Thr-14, Tyr-15) did not account for the lack of cyclin E-Cdk2 kinase activity in senescent cells, i.e., even though approximately one-half of the cyclin E-associated Cdk2 was phosphorylated on Thr-160, treatment with Cdc25 phosphatase to dephosphorylate Thr-14 and Tyr-15 did not increase activity. (asm.org)
- The finding that senescent HDF contain elevated amounts of the ubiquitously acting cyclin-dependent kinase inhibitor (CKI) p21 Sdi1,Cip1,Waf1 (p21) ( 40 ) suggested instead that cyclin E-Cdk2 complexes in senescent cells might be inactivated by increased binding of p21. (asm.org)
- Upon receiving appropriate growth signals, pRb is hyperphosphorylated by cyclin-dependent kinase (cdk) complexes such as cyclin D/cdk4/6 and cyclin E/cdk2 ( 6 ). (aacrjournals.org)
- In contrast with the negative cell-cycle regulation, p21 may also serve as an assembly factor for cyclin D-CDK4/6 complexes, thus promoting cyclin D-dependent events, and downstream activation of cyclin E-CDK2 [ 7 , 8 ]. (intechopen.com)
- Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
- Reference: Phosphorylation of human DNA polymerase lambda by the cyclin-dependent kinase Cdk2/cyclin A complex is modulated by its association with proliferating cell nuclear antigen. (neb.com)
- In this work, we searched by affinity chromatography for novel partners and we identified the cyclin-dependent kinase Cdk2 as novel partner of Pol lambda. (neb.com)
- Pol lambda is phosphorylated in vitro by several Cdk/cyclin complexes, including Cdk2/cyclin A, in its proline-serine-rich domain. (neb.com)
- While the polymerase activity of Pol lambda was not affected by Cdk2/cyclin A phosphorylation, phosphorylation of Pol lambda was decreased by its interaction with PCNA. (neb.com)
- p21 Cip1 (alternatively p21 Waf1 ), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 , is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated with inhibition of CDK2 . (wikipedia.org)
- The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin - CDK2 , - CDK1 , and - CDK4 /6 complexes, and thus functions as a regulator of cell cycle progression at G 1 and S phase . (wikipedia.org)
- Experiments looking at CDK2 activity within single cells have also shown p21 to be responsible for a bifurcation in CDK2 activity following mitosis, cells with high p21 enter a G 0 /quiescent state, whilst those with low p21 continue to proliferate. (wikipedia.org)
- also found that γ-irradiation of fibroblasts induced a p53 and p21 dependent cell cycle arrest, here p21 was found bound to inactive cyclin E / CDK2 complexes. (wikipedia.org)
- 1993). CDKN1A binds and inactivates CDK2 in complex with cyclin A (CCNA) or E (CCNE), thus preventing G1/S transition (Harper et al. (wikipathways.org)
- Finally, we show that multiprotein complex formation involving p45 SKP2 -CUL‐1 and p19 SKP1 is governed, in part, by periodic, S phase‐specific accumulation of the p45 SKP2 subunit and by the p45 SKP2 ‐bound cyclin A-CDK2. (embopress.org)
- The dependency of p45 SKP2 -p19 SKP1 complex formation on cyclin A-CDK2 may ensure tight coordination of the activities of the cell cycle clock with those of a potential ubiquitin conjugation pathway. (embopress.org)
- In mammalian cells, cyclin A, in complex with its catalytic partner CDK2, has been established as a key promoter for progression through the S phase of the cell cycle (for review, see Heichmann and Roberts, 1994 ). (embopress.org)
- Unexpectedly, p27 protein expression was highest in cells of the proliferative crypt compartment where it bound both cdk2 and cdk4. (elsevier.com)
- Cdk2 activity was increased in crypt cells from p27 Δ51/Δ51 mice, although cyclin D-associated kinase activity was unchanged (indeed, cyclin D1/2-cdk4 complex levels were reduced). (elsevier.com)
- Importantly, cdk2 activity was unchanged in crypt cells from p21 -/- mice, which do not develop intestinal tumors. (elsevier.com)
- Conclusions: We propose that p27 contributes to intestinal epithelial homeostasis by regulating cdk2 activity in proliferating cells, thus gating cell cycle progression and suppressing intestinal neoplasia. (elsevier.com)
- 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)
- p27 Kip1 has classically been regarded as a cell cycle inhibitor based on its potent inhibitory activity of cyclin E/Cdk2 ( 42 ) and the observation that its forced expression results in G 1 arrest (reviewed in reference 49 ). (asm.org)
- However, p27 is also required for assembly and function of cyclin D1/Cdk4 complexes during early G 1 ( 7 , 8 , 48 , 55 ), suggesting that p27 may play a dual role, permitting early G 1 progression (via assembly of cyclin D/Cdk4) and restraining late G 1 progression (via repression of cyclin E/Cdk2). (asm.org)
- The encoded protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. (abnova.com)
- This protein is an essential element of the cyclin A-CDK2 S-phase kinase. (abnova.com)
- Taken together, the biochemical and structural results delineate a druggable inhibitor site on the surface of PCNA that may be exploited in the design of peptidomimetics, which will act independently of cyclin-groove inhibitors. (rcsb.org)
- A unique feature of p21 that distinguishes it from the other cyclin-dependent kinase (CDK) inhibitors is its ability to associate with the proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerases delta and epsilon. (mendeley.com)
- p21/WAF1, also known as cip1 and cyclin-dependent kinase interacting protein 1, is a 21kD protein that belongs to the CDI family of cyclin-dependent kinase inhibitors. (lsbio.com)
- CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
- HTLV-1 Tax can induce senescence by up-regulating the levels of cyclin-dependent kinase inhibitors p21 CIP1/WAF1 and p27 KIP1 . (biomedcentral.com)
- The binding of p21 to CDK complexes occurs through p21's N-terminal domain, which is homologous to the other CIP/KIP CDK inhibitors p27 and p57 . (wikipedia.org)
- Activation of CDKs is regulated by the availability of their cognate cyclin subunit, positive and negative regulatory phosphorylation and association with CDK inhibitors (CKIs) ( Morgan, 1995 ). (embopress.org)
- As expected, expression of the cdk inhibitors p21, p57, and p16 was highest in differentiated villus cells. (elsevier.com)
- Inhibitors of mammalian target of rapamycin (mTOR), including temsirolimus have efficacy in the treatment of renal cell cancer (RCC) and are currently under investigation in other malignancies. (aacrjournals.org)
- The differentiation was accompanied by a growth arrest and the upregulation of cyclin-dependent kinase inhibitors, p27 and p57, as well as cyclin D 1 , whereas cyclin A was downregulated. (asnjournals.org)
- 4,5 ERK1/2 signaling is also necessary for the degradation or downregulation of cyclin- dependent kinase (CDK) inhibitors, such as p21 waf1 (p21) and particularly p27 kip1 (p27), thereby eliminating their growth-suppressive activities. (ahajournals.org)
- Western blot showed increased levels of p53 and p21 WAF-1/Cip1 in rAd.p53 infected cells, but not in rAd.GFP and uninfected cells. (bmj.com)
- The Brn-3a transcription factor inhibits the pro-apoptotic effect of p53 and enhances cell cycle arrest by differentially regulating the activity of the p53 target genes encoding Bax and p21(CIP1/Waf1). (wikipathways.org)
- We have found recently that Tax can commit eukaryotic cells into a senescence-like state with dramatically up-regulated expression of p21 CIP1/WAF1 (p21) and p27 KIP1 (p27) [ 23 ]. (biomedcentral.com)
- Similar effects are observed in cells expressing p21CDK-, a mutant impaired in the interaction with CDKs, but not in cells expressing p21PCNA-, a mutant deficient for the interaction with PCNA. (mendeley.com)
- Independently of its S phase function, and similarly to what it has been found in mammal cells, during maize germination, PCNA also associates to D type cyclins and to A type Cdks . (scielo.org.mx)
- Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
- Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
- Each phase of cell cycle is regulated by a unique set of CDKs which are in turn positively regulated by onset of particular cyclin partners. (omicsonline.org)
- Besides cyclins, the activation of CDKs requires the presence of CDK-activating kinase (CAK). (omicsonline.org)
- A dysregulation of these cdks leads to an uncontrolled cell division ending up in tissue cancerization (for a review, see Ref. 1 ). (mcponline.org)
- The irreversible G 1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G 1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). (asm.org)
- Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. (asm.org)
- Based on pRb's direct ability to regulate the cell cycle through phosphorylation status, and that pRb phosphorylation is altered following exposure to free radicals and other inflammatory species ( 7 - 10 ), we hypothesized that pRb phosphorylation status and its pathway are dysregulated in ulcerative colitis in vivo . (aacrjournals.org)
- Finally, Pol lambda is also phosphorylated in vivo in human cells and this phosphorylation is modulated during the cell cycle. (neb.com)
- Phosphorylation of a substrate protein can redirect its overall function, causing it to alter key biological functions, including cell cycle control and signal transduction. (pubmedcentralcanada.ca)
- Under a variety of stress conditions, TP53 (p53), stabilized by stress-induced phosphorylation at least on S15 and S20 serine residues, can induce the transcription of genes involved in cell cycle arrest. (wikipathways.org)
- Literature reveals that there there exists a stringent balance between the de novo synthesis and targeted degradation of cyclins by the phosphorylation of specific residues, which prompt their recruitment and incorporation into multiprotein destruction complexes (Skp 1-Cullin-F-box protein (SCF) or anaphasepromoting complex/cyclosome (APC/C) and subsequent degradation within the proteasome [ 3 ]. (omicsonline.org)
- Phosphorylation at Tyr-211 by EGFR stabilizes chromatin-associated PCNA. (stjohnslabs.com)
- Following cytokine withdrawal or PI3K inhibition, there was a loss of FOXO3A phosphorylation, resulting in increased expression of FasL and Fas at the cell surface. (ubc.ca)
- Following cytokine withdrawal or PI3K inhibition, there was a loss of FOX03A phosphorylation, resulting in increased expression of FasL and Fas at the cell surface. (ubc.ca)
- Together, these data demonstrate that RPA and the MRN complex co-localize and interact after HU- or UV-induced replication stress and suggest that protein phosphorylation may play a role in this interaction. (labome.org)
- Lo Y, Ho P, Chen M, Hugo E, Ben Jonathan N, Wang S. Phosphorylation at tyrosine 114 of Proliferating Cell Nuclear Antigen (PCNA) is required for adipogenesis in response to high fat diet. (labome.org)
- 7 mTOR, which can be blocked by the immunosuppressant rapamycin after the latter has formed a complex with the immunophilin FK-binding protein (FKBP), 8 possesses kinase activity that is required for p70 S6 kinase activation 9 and may also be directly involved in 4E-BP1 phosphorylation. (ahajournals.org)
- 12 mTOR may sense nutrient availability within the cell and provide basal phosphorylation of p70 S6 kinase, whereas PI 3-kinase may mediate subsequent mitogen-induced phosphorylation of p70 S6 kinase. (ahajournals.org)
- In the present study, we tested the hypothesis that phosphorylation of 4E-BP1 and p70 S6 kinase by PI 3-kinase and mTOR are critical events during the mitogenic stimulation of coronary artery smooth muscle cells (CASMCs) in vitro and in response to vascular injury in vivo. (ahajournals.org)
- We present the x-ray crystal structure of PCNA complexed with a 16-mer peptide related to p21 that binds with a Kd of 100 nM. (rcsb.org)
- Cyclin D is a protein that binds and activates a Cdk . (scielo.org.mx)
- 2002). BTG2 binds to the CCR4-NOT complex and promotes mRNA deadenylation activity of this complex. (wikipathways.org)
- PCNA binds to flap endonuclease 1 (FEN-1), a structure-specific endonuclease involved in DNA replication. (sdbonline.org)
- The conserved FEN-1 C terminus binds proliferating cell nuclear antigen (PCNA) and positions FEN-1 to act primarily as an exonuclease in DNA replication, in contrast to its endonuclease activity in DNA repair. (sdbonline.org)
- Moreover, they strongly suggest that ERK8's PIP box binds to PCNA only when the kinase is associated with chromatin. (rupress.org)
- Analysis of DNA replication in cells constitutively expressing cyclin E at levels similar to those observed in a subset of tumor-derived cell lines indicates that initiation of replication and possibly fork movement are severely impaired. (rupress.org)
- Moreover, K-ras gene mutation enhances motility of lung adenocarcinoma cells via Akt activation (18), and radioresistance of K-ras-mutated human tumor is mediated through the epidermal growth factor receptor-dependent PI3K-Akt pathway (19). (redorbit.com)
- The majority of chemotherapeutic agents used in clinics are highly toxic to both tumor cells and normal tissues due to the lack of specificity. (dovepress.com)
- As translocation across the plasma membrane is a limiting step for delivery of macromolecules, these polypeptides were utilized in a pancreatic xenograft model to study the plasma clearance, biodistribution, tumor accumulation, and tumor reduction capabilities of the polypeptide with and without a cell-penetrating peptide. (dovepress.com)
- Macromolecules are gaining interest in drug delivery because they preferentially accumulate due to their ability to extravasate into the tumor much more readily compared to a normal cell well. (dovepress.com)
- The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. (hindawi.com)
- Kanglaite(KLT) injection is an anti-tumor new drug which extracts from Chinese medicine-coix seed with modern advanced pharmaceutical technology, it is also a new biphase extended-spectrum anticancer medicine, the food and drug administration(FDA) of United States also approved a phase II trial of KLT to test its efficacy in treating non-small-cell lung cancer. (studyres.com)
- Kanglaite(KLT) injectionis a diphasic broad-spectrum anti-tumor new drug which has depressant effect on many kinds of tumor cells, it is extracted from the chinese crude drug-coixenolide [5,and made use of the latest and most complex modern high technologies in process of preparation . (studyres.com)
- The histopathological diagnosis had been revised and all cases were stained by immunohistochemical technique with Ki-67, PCNA, and CD34 tumor markers. (omjournal.org)
- A significant correlation was found between Ki-67, PCNA labeling indices, and MVD (microvessel density) detected by CD34, and between the clinicopathological variables of astrocytomas (age and grade of tumor). (omjournal.org)
- CDK/cyclin complexes regulate each phase of the cell cycle and the breakdown of this regulation in any phase results in uncontrolled growth and thus tumor formation. (omicsonline.org)
- The explanation is multifactorial, determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immune response. (mdpi.com)
- Promising laboratory results have not been translated to improved clinical outcomes, and this appears to be determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immunity. (mdpi.com)
- Metastatic spread of tumor cells through the organism depends on proteolytic activity and is the death determinant for cancer patients. (aacrjournals.org)
- Paradoxically, increased expression of tissue inhibitor of metalloproteinases-1 (TIMP-1), a natural inhibitor of several endometalloproteinases, including matrix metalloproteinases and a disintegrin and metalloproteinase-10 (ADAM-10), in cancer patients is negatively correlated with their survival, although TIMP-1 itself inhibits invasion of some tumor cells. (aacrjournals.org)
- Metastasis and progressive scattering of tumor cells throughout tissues is the main cause of organ failure and subsequent death of cancer patients. (aacrjournals.org)
- ref. 5 ) can reduce tumor cell invasion ( 6 , 7 ). (aacrjournals.org)
- Tumor cell invasion and metastasis are the primary determinants of the survival of cancer patients ( 13 ). (aacrjournals.org)
- HGF stimulates metastasis of diverse tumor cells ( 15 ) and elevated levels of circulating HGF ( 18 ) or aberrant activity of cMet ( 14 ) has been detected in patients with many cancer types, including non-Hodgkin's lymphoma ( 19 ) and colorectal cancer ( 14 ). (aacrjournals.org)
- Recent studies show that down regulation of PTTG in tumor cell lines and tumors in vivo results in suppression of tumor growth, suggesting its important role in tumorigenesis. (biomedcentral.com)
- To eliminate these remaining cells, various adjuvant chemotherapy strategies are employed based on cancer stage, tumor grade, and other health concerns. (biomedcentral.com)
- Pituitary tumor transforming gene (PTTG) is an oncogene involved in cell cycle regulation and sister chromatid separation. (biomedcentral.com)
- A TAMR/MCF-7 cells xenograft model was established to investigate the inhibitory effect of SAHA on tumor growth in vivo. (medsci.org)
- In mice bearing the TAMR/MCF-7 cell xenografts, SAHA significantly reduced the tumor growth and weight, without apparent side effects. (medsci.org)
- The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. (abnova.com)
- However, a tumor of this size already contains several hundred million cells. (mcponline.org)
- From the cellular point of view, given the fact that a single cell can lead to the development of a whole tumor (clonal origin of cancer), it is already late when a breast tumor is detected by mammography. (mcponline.org)
- Depending on the cellular and histological origin of the cancer cells and on the evolution of the disease, a broad range of breast tumor types have been described. (mcponline.org)
- We hypothesized that the covalent linkage of a known tumor antigen peptide to beta-2-microglobulin ( b 2 m) would increase peptide immunogenicity and, therefore, in vivo effectiveness as an antitumor vaccine in BALB/c mice. (cognizantcommunication.com)
- The iL3 peptide fusion protein (iL3-L12-h b 2 m) was developed based on the mutant iL3 peptide, derived from the L3 ribosomal protein, and expressed in the mutagenized murine fibroblastic tumor cell line, BCA34. (cognizantcommunication.com)
- The quaternary complex shows little direct interaction between PCNA and cyclin, giving p21 the role of an adaptor molecule. (rcsb.org)
- The main role of p21 is cell-cycle regulation, performed by inhibiting the activity of cyclin-CDK complexes thanks to direct interaction through specific sequences (termed CDK and Cy motifs) in the N-terminal domain of the protein [ 10 - 13 ]. (intechopen.com)
- One such protein is p21Cip1, which inhibits DNA replication through its interaction with PCNA, while allowing repair to continue. (sdbonline.org)
- An interaction has been identified between PCNA and the structure specific nuclease, Fen1, which is involved in DNA replication. (sdbonline.org)
- There is a direct physical interaction of PCNA with xeroderma pigmentosum (XP) G, a structure-specific repair endonuclease that is homologous to FEN-1. (sdbonline.org)
- SET8 degradation requires a conserved degron responsible for its interaction with PCNA and recruitment to chromatin where ubiquitylation occurs. (rupress.org)
- The truncated analyses indicated that the C-terminal of Arabidopsis RFC2/3/4/5 and rice RFC1/2 is essential for binding PCNA while the region of rice RFC3/4/5 mediating interaction with PCNA distributed both at the N- and C-terminal. (springer.com)
- On the other hand, we found that the C- and N-terminal of Arabidopsis and rice PCNA contribute equally to PCNA-PCNA interaction, and the interdomain connecting loop (IDCL) domain and C-terminal of PCNAs are indispensable for interacting RFC subunits. (springer.com)
- We explored a role of Mcl-1 in cell cycle regulation, DNA damage checkpoint response, and cellular differentiation and found an interaction between Mcl-1 and the cell cycle regulatory protein Cdk-1 in nuclear compartment. (ubc.ca)
- We identified a PCNA-interaction protein motif (PIP box) in the SMCX protein. (biomedcentral.com)
- Using site-directed mutagenesis, we found that the amino acids of the SMCX PIP box are involved in the association of SMCX with PCNA and its interaction with chromatin. (biomedcentral.com)
- Further, we identified a aconserved sequence motif, [NQ]xx(L/I/M/V)xx (F/Y/W), called the PCNA-interaction protein motif (PIP box) in the SMCX protein. (biomedcentral.com)
- Each red dot represents the detection of protein-protein interaction complex. (abnova.com)
- Relatively close by, in the middle of ERK8, resides a PCNA-interacting peptide (PIP) box required for the interaction with PCNA ( Warbrick, 1998 ). (rupress.org)
- Using the technique of Chromatin Immunoprecipitation, we have detected the formation of complexes between the homotrimer protein ring Proliferating Cell Nuclear Antigen, PCNA, and two fundamental regulators of the cell cycle, CdkA and Cyclin D4;2 along germination of maize seeds. (scielo.org.mx)
- In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. (cnrs.fr)
- Here, we collate what is known about the various cell cycle events and their regulators throughout the Plasmodium life-cycle, highlighting the differences between Plasmodium , model organisms and other apicomplexan parasites and identifying areas where further study is required. (springer.com)
- Such a complex life-cycle presumably requires sophisticated global and local regulators, involving refined checkpoint and DNA repair mechanisms [ 3 ], yet these are currently only poorly understood. (springer.com)
- The effect on PCNA stability seemed to be highly specific, as depletion of ERK8 caused codepletion of PCNA but did not lead to a decrease in steady-state levels of a variety of other cell cycle regulators. (rupress.org)
- Cells expressing lamin A mutants G232E and Q294P, in which HECW2 is upregulated, show increased proteasomal degradation of PCNA and lamin B1 most likely mediated by HECW2. (deepdyve.com)
- Tax increases p27 KIP1 protein stability by activating the anaphase promoting complex/cyclosome (APC/C) precociously, causing degradation of Skp2 and inactivation of SCF Skp2 , the E3 ligase that targets p27 KIP1 . (biomedcentral.com)
- However, although the fundamental mechanisms for cell-cycle control appear to be well conserved among species, the G 1 marker based on the SCF Skp2 -mediated degradation of human Cdt1 did not work in fish cells, probably because the marker was not ubiquitinated properly by a fish E3 ligase complex. (pnas.org)
- One major challenge to relieve cancer burden is to develop highly effective drugs with specificity on cancers but little or no side effects on normal mammalian cells. (hindawi.com)
- PCNA is highly conserved between mammalian species and other vertebrates. (bio-rad-antibodies.com)
- The tight regulation implies that Cdt1 control is especially critical for the regulation of DNA replication in mammalian cells. (biomedcentral.com)
- In this review, recent insights into Cdt1 function and regulation in mammalian cells are discussed. (biomedcentral.com)
- In this review, recent insights into Cdt1 function and regulation in mammalian cells are summarized and questions that remain to be solved in the future are also discussed. (biomedcentral.com)
- The mammalian target of rapamycin (mTOR) inhibitor temsirolimus has exhibited promising anticancer activity for the treatment of renal cell cancers (RCC). (aacrjournals.org)
- p70 S6 kinase, a target of PI 3-kinase and the mammalian target of rapamycin, was rapidly activated on growth factor stimulation of quiescent coronary artery smooth muscle cells and after balloon injury of rat carotid arteries. (ahajournals.org)
- The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
- Association of TP53 (p53) with various transcriptional co-factors can promote, inhibit or provide specificity towards either transcription of cell cycle arrest genes or transcription of cell death genes. (wikipathways.org)
- We hypothesized that estrogen metabolite, 16α-hydroxyestrone (16αOHE1), stimulates nicotinamide adenine dinucleotide phosphate oxidase (Nox)-induced reactive oxygen species (ROS) generation and proliferative responses in human pulmonary artery smooth muscle cells (hPASMCs) and that in PAH aberrant growth signaling promotes vascular remodeling. (ahajournals.org)
- In the mature state, podocytes lose their proliferative capacity and develop specialized junctions between the cell body and the glomerular basement membrane, known as the focal adhesion complex, and junctions between interdigitating foot processes, known as the slit diaphragm or membrane. (asnjournals.org)
- The entry of vascular cells into the cell cycle plays an important role in the pathogenesis of proliferative vascular diseases, such as postangioplasty restenosis, transplant vasculopathy, vein graft disease, and primary atherosclerosis. (ahajournals.org)
- Deregulation of cyclin E expression has been associated with a broad spectrum of human malignancies. (rupress.org)
- Expression of PCNA is under the control of E2F transcription factor-containing complexes. (wikipedia.org)
- In quiescent young HDF, cyclin D1 and cyclin E are present in low amounts, but upon serum stimulation both their expression and their associated kinase activities increase during the mid and late G 1 phases, respectively ( 14 , 50 ). (asm.org)
- Objective To analyze the expression of splicing factors in gastric cancer using bioinformatics methods and investigate the effect of aberrantly expressed serine/arginine-rich splicing factor(SRSF10)on the phenotype of gastric cancer cells. (bvsalud.org)
- Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. (biomedcentral.com)
- Firstly, we showed that CD44 expression was increased in several kinds of leukemia patients and K562 cells. (biomedcentral.com)
- The instability of Wnt/β-catenin pathway induced by increased expression of p-β-catenin resulted in a decreased nuclear accumulation in CD44 silenced K562 cells. (biomedcentral.com)
- High-level expression and purification of a recombinant human alpha-1, 3-fucosyltransferase in baculovirus-infected insect cells. (termsreign.gq)
- Recombinant human activated protein C upregulates cyclooxygenase-2 expression in endothelial cells via binding to endothelial cell protein C receptor and activation of protease-activated receptor-1. (termsreign.gq)
- Immunohistochemical Expression of Ki-67, PCNA and CD34 in Astrocytomas: A Clinicopathological Study. (omjournal.org)
- identified a protein p21 (WAF1) which was present in cells expressing wild type p53 but not those with mutant p53, moreover constitutive expression of p21 led to cell cycle arrest in a number of cell types. (wikipedia.org)
- E2F7 contributes to G1 cell cycle arrest by repressing transcription of E2F1, a transcription factor that promotes expression of many genes needed for G1/S transition (Aksoy et al. (wikipathways.org)
- Bedelbaeva K, Snyder A, Gourevitch D, Clark L, Zhang X-M, Leferovich J, Cheverud JM, Lieberman P, Heber-Katz E. Lack of p21 expression links cell cycle control and appendage regeneration in mice . (wikipedia.org)
- expression of cyclin D1, D2, and cyclin E showed little change. (elsevier.com)
- In the trypsin (TrypLE)-prepared BCECs, BrdU incorporation decreased whereas nuclear ZONAB expression increased and became stable from day 3 to 7. (molvis.org)
- In contrast, in the collagenase-A-prepared BCECs, we observed preserved ZO-1 integrity, invariant nuclear ZONAB expression, and dense cortical F-actin expression, and BrdU incorporation was invariant from days 1 to 7. (molvis.org)
- Y-27632 did not increase BrdU incorporation and nuclear ZONAB expression in the TrypLE-prepared and the collagenase-A-prepared BCECs. (molvis.org)
- western blot and real-time PCR were employed to observe the expression of p21 in HCC cells. (biomedcentral.com)
- and analyzing the sample for increased or decreased expression levels of at least three DNA repair genes as compared to a control cell that is not exposed to the potentially genotoxic or carcinogenic compound. (patentsencyclopedia.com)
- We also confirmed that miR-17 exerted this function by directly targeting RND3 in vitro , and that the expression of miR-17 was negatively correlated with that of RND3 in CRC tissues and CRC cells. (portlandpress.com)
- In these three renal cell lines, there was no significant difference in TCF-4 mRNA expression before and after 5-Aza-2′-deoxycytidine treatment, and there appeared to be no splicing isoforms in the region between exon 1 and exon 11. (aacrjournals.org)
- On day 3 and7 after grafting, the vein grafts were extracted, and analyzed morphologically by haematoxylin eosin (H&E), and assessed by immunohistochemistry for expression of Ki-67 and proliferating cell nuclear antigen (PCNA). (biomedcentral.com)
- However, over-expression of Mcl-1 in these cells did not appear to enhance cellular differentiation. (ubc.ca)
- The ability of β-cell mass to expand was correlated with higher levels of Bmi1, a polycomb group protein that is known to regulate the Ink4a locus, and decreased levels of p16 Ink4a expression in the β-cells. (diabetesjournals.org)
- These data are consistent with cell cycle protein expression during podocyte maturation in vivo . (asnjournals.org)
- Both cobblestone and arborized cells originated from podocytes, as evidenced by the expression of a podocyte-specific O-acetylated ganglioside ( 9 ) and the WT-1 protein, which is restricted to podocytes in the adult kidney ( 8 ). (asnjournals.org)
- The differentiation of arborized cells was reflected by the formation of processes and the expression of synaptopodin, which was never detected in cobblestones ( 8 ). (asnjournals.org)
- In another proof of principle, we coupled the NAPPA with the SNAP tag E. coli cell-free expression system. (jnanoworld.com)
- Interestingly, expression of the autophagic cell death markers, LC3-II and beclin-1, was significantly increased in TAMR/MCF-7 cells treated with SAHA. (medsci.org)
- Furthermore, we also investigated release of inflammatory cytokines and chemokines from human RA synovial cell cultures, and observed no effect of PPI-2458 on spontaneous expression of cytokines and chemokines, or indeed on the angiogenic molecule vascular endothelial growth factor (VEGF). (biomedcentral.com)
- Fibroblasts constitute over 90% of nonmyocyte cells in the heart ( 2 ), yet occupy only one third of cardiac tissue ( 9 ). (physiology.org)
- In contrast with eccentric hypertrophy (elongation) of myocytes ( 60 ), fibroblasts proliferate and become myofibroblasts, a process that enhances ECM secretion and deposition ( 51 , 57 ). (physiology.org)
- In eukaryotic cells, replication of genomic DNA initiates from multiple replication origins distributed on multiple chromosomes. (biomedcentral.com)
- Therefore, the amount of DNA replicated from each origin is relatively short, allowing genome size to expand during the evolution of eukaryotic cells. (biomedcentral.com)
- Dominant negative alleles of Akt have been reported to block cell survival and to induce an apoptotic response (14). (redorbit.com)
- The studies described here were designed to elucidate the signaling pathway(s) that modulate the apoptotic potential of Troglitazone (TRG), an artificial PPARγ ligand in hepatocellular carcinoma (HCC) cells. (jmolecularsignaling.com)
- 2007). Binding of POU4F1 (BRN3A) to TP53 also stimulates transcription of cell cycle arrest genes while inhibiting transcription of pro-apoptotic genes (Budhram-Mahadeo et al. (wikipathways.org)
- Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. (wikipathways.org)
- 1993). Nevertheless, under prolonged stress, the cell destiny may be diverted towards an apoptotic outcome. (wikipathways.org)
- However, apoptotic cells were not obviously found in all grafts on day 3 and 7 post surgery. (biomedcentral.com)
- Although SAHA induced G2/M phase arrest of cell cycle, apoptotic cell death was very low, which is correlated with the slight change in the activation of caspases and PARP cleavage. (medsci.org)
- These results suggest that SAHA can induce caspase-independent autophagic cell death rather than apoptotic cell death in TAMR/MCF-7 cells. (medsci.org)
- When Ciz1 and p21(Cip/Waf1) were individually overexpressed in U2-OS cells, they mostly localized in the nucleus. (elsevier.com)
- These data indicate that Ciz1 is a unique nuclear protein that regulates the cellular localization of p21(Cip/Waf1). (elsevier.com)
- Białko p21 (WAF1) jest w stanie oddziaływać z jądrowym antygenem komórek proliferujących ( proliferating cell nuclear antigen − PCNA), czynnikiem dodatkowym polimerazy DNA , i tym samym odgrywać rolę regulatora zarówno przy replikacji materiału genetycznego w fazie S jak i przy naprawie łańcucha . (wikipedia.org)
- In addition, Pol lambda has been shown to interact with the replication clamp proliferating cell nuclear antigen (PCNA) in vitro and in vivo. (neb.com)
- PCNA is pivotal to the activation of these pathways and the choice as to which pathway is utilised by the cell. (wikipedia.org)
- After exposure to genotoxic agents, cells activate DNA damage response pathways consisting of a signaling cascade (cell cycle checkpoints), and of DNA repair processes able to recognize and remove a great number of DNA lesions [ 1 ]. (intechopen.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)
- 2 The Ras proto-oncogene is a central component of mitogenic signaling pathways and is essential for cells to exit into a quiescent state (G0) and to pass through the G1-S transition of the cell cycle. (ahajournals.org)
- Our identification of downstream targets of Sox17 thus defines signaling pathways and molecular mechanisms in OPCs that are regulated by Sox17 during cell cycle exit and the onset of differentiation in oligodendrocyte development. (jneurosci.org)
- Results A total of 48 splicing factors were identified in gastric cancer by a series of bioinformatics techniques,of which 35 were up-regulated and 13 were down-regulated.The splicing factor SRSF10,which was up-regulated,was selected for further study.It was found that the gastric cancer cells after SRSF10 knockdown proliferated more slowly and had lower migration ability than normal gastric cancer cells. (bvsalud.org)
- Sox17 knockdown also increases the levels of cyclin D1, Axin2, and activated β-catenin. (jneurosci.org)
- We concluded that tafazzin knockdown interrupts the NVF cell cycle and this in turn may contribute to fibrosis and dilated cardiomyopathy in Barth syndrome. (physiology.org)
- Neoplastic hepatic cells not only loose their ability to regulate growth, but they also become dedifferentiated and thereby loose their differentiated function. (jmolecularsignaling.com)
- The cell cycle is tightly regulated to control cell growth. (asm.org)
- Our findings demonstrate that in PAH-hPASMCs, 16αOHE1 stimulates redox-sensitive cell growth primarily through Nox1. (ahajournals.org)
- Because of its competitive antagonism, tamoxifen is binding to the ER and hence blocking breast cancer cell growth [ 4 ]. (medsci.org)
- On the therapeutic side, practical consequences for treatment, derived from a better understanding of the molecular basis of cancer cell growth, are now emerging. (mcponline.org)
- In contrast to findings in other cell types, growth factor- or balloon injury-induced downregulation of the cell cycle inhibitor p27 Kip1 was not affected by rapamycin treatment. (ahajournals.org)
- This review focusses on the unusual cell cycles of Plasmodium , which may present a rich source of novel drug targets as well as a topic of fundamental biological interest. (springer.com)
- Because the consensus motif for the TCF-4 binding site (A/TA/TCAAAG) is present in the promoter region (6 , 7 , 8 , 9 , 10) , c-myc, cyclin D1, c-jun, and MMP7 are considered targets for the Wnt signaling pathway. (aacrjournals.org)
- Flap EndoNuclease-1 (FEN-1) and the processivity factor proliferating cell nuclear antigen (PCNA) are central to DNA replication and repair. (sdbonline.org)
- PCNA is a highly conserved protein, with minimal differences in yeasts, mammals, humans or plants [2 and a conserved molecular mass of around 29 kDa. (scielo.org.mx)
- These results indicated that Arabidopsis and rice PCNAs are highly conserved in sequence, structure and pattern of interacting with other PCNA monomer. (springer.com)
- Under most cellular conditions, pRb controls cell cycle entry by sequestering the E2F family of transcription factors. (aacrjournals.org)
- While the general global genome repair (GGR) removes DNA damage from the entire genome, the cell has set up a more specialized transcription‐coupled repair (TCR) subpathway that corrects DNA lesions located on the actively transcribed strand ( Mullenders and Berneburg, 2001 ). (embopress.org)
- Damage of DNA, hence potentially deleterious mutations, caused by such factors as UV, free radicals, and active transcription, needs to be repaired before these mutations are passed to daughter cells. (sigmaaldrich.com)
- These enzymes are typically part of multi-component complexes that repress transcription. (sigmaaldrich.com)