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.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
A 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.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
Highly differentiated epithelial cells of the visceral layer of BOWMAN CAPSULE of the KIDNEY. They are composed of a cell body with major CELL SURFACE EXTENSIONS and secondary fingerlike extensions called pedicels. They enwrap the KIDNEY GLOMERULUS capillaries with their cell surface extensions forming a filtration structure. The pedicels of neighboring podocytes interdigitate with each other leaving between them filtration slits that are bridged by an extracellular structure impermeable to large macromolecules called the slit diaphragm, and provide the last barrier to protein loss in the KIDNEY.
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.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
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.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
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.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A cyclin 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.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A 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.
The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis.
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.
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.
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.
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.
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.
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.
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 kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
A 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.
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.
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.
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.
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.
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.
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
A 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.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
A cell line derived from cultured tumor cells.
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.
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.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
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.
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)
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.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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.
A family of proteins that share the F-BOX MOTIF and are involved in protein-protein interactions. They play an important role in process of protein ubiquition by associating with a variety of substrates and then associating into SCF UBIQUITIN LIGASE complexes. They are held in the ubiquitin-ligase complex via binding to SKP DOMAIN PROTEINS.
An aspect of protein kinase (EC in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
A quiescent state of cells during G1 PHASE.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
Protein kinase that drives both the mitotic and meiotic cycles in all eukaryotic organisms. In meiosis it induces immature oocytes to undergo meiotic maturation. In mitosis it has a role in the G2/M phase transition. Once activated by CYCLINS; MPF directly phosphorylates some of the proteins involved in nuclear envelope breakdown, chromosome condensation, spindle assembly, and the degradation of cyclins. The catalytic subunit of MPF is PROTEIN P34CDC2.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
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.
A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.
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.
A multifunctional CDC2 kinase-related kinase that plays roles in transcriptional elongation, CELL DIFFERENTIATION, and APOPTOSIS. It is found associated with CYCLIN T and is a component of POSITIVE TRANSCRIPTIONAL ELONGATION FACTOR B.
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.
Echinoderms having bodies of usually five radially disposed arms coalescing at the center.
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.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
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.
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. It contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
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.
A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.
A family of structurally-related proteins that were originally identified by their ability to complex with cyclin proteins (CYCLINS). They share a common domain that binds specifically to F-BOX MOTIFS. They take part in SKP CULLIN F-BOX PROTEIN LIGASES, where they can bind to a variety of F-BOX PROTEINS.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.
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.
Tumors or cancer of the human BREAST.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).
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.
A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.
Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.
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.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
A CYCLIN C dependent kinase that is an important component of the mediator complex. The enzyme is activated by its interaction with CYCLIN C and plays a role in transcriptional regulation by phosphorylating RNA POLYMERASE II.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
The process by which a DNA molecule is duplicated.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Cdh1 is an activator of the anaphase-promoting complex-cyclosome, and is involved in substrate recognition. It associates with the complex in late MITOSIS from anaphase through G1 to regulate activity of CYCLIN-DEPENDENT KINASES and to prevent premature DNA replication.
A cyclin-dependent kinase that forms a complex with CYCLIN C and is active during the G1 PHASE of the CELL CYCLE. It plays a role in the transition from G1 to S PHASE and in transcriptional regulation.
Elements of limited time intervals, contributing to particular results or situations.
Transport proteins that carry specific substances in the blood or across cell membranes.
Cellular proteins encoded by the c-mos genes (GENES, MOS). They function in the cell cycle to maintain MATURATION PROMOTING FACTOR in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time.
A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.
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.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.
A 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.
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.
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.

Cyclin I protects podocytes from apoptosis. (1/7)

The limited regenerative capacity of the glomerular podocyte following injury underlies the development of glomerulosclerosis and progressive renal failure in a diverse range of kidney diseases. We discovered that, in the kidney, cyclin I is uniquely expressed in the glomerular podocyte, and have constructed cyclin I knock-out mice to explore the biological function of cyclin I in these cells. Cyclin I knock-out (-/-) podocytes showed an increased susceptibility to apoptosis both in vitro and in vivo. Following induction of experimental glomerulonephritis, podocyte apoptosis was increased 4-fold in the cyclin I -/- mice, which was associated with dramatically decreased renal function. Our previous data showed that the Cdk inhibitor p21(Cip1/Waf1) protects podocytes from certain apoptotic stimuli. In cultured cyclin I -/- podocytes, the level of p21(Cip1/Waf1) was lower at base line, had a shorter half-life, and declined more rapidly in response to apoptotic stimuli than in wild-type cells. Enforced expression of p21(Cip1/Waf1) reversed the susceptibility of cyclin I -/- podocytes to apoptosis. Cyclin I protects podocytes from apoptosis, and we provide preliminary data to suggest that this is mediated by stabilization of p21(Cip1/Waf1).  (+info)

Serum proteomic-based analysis of pancreatic carcinoma for the identification of potential cancer biomarkers. (2/7)

To identify new biomarkers that improve the early diagnosis and lead to possible therapeutic targets in pancreatic carcinoma, we performed a proteomic approach to compare serum protein expression patterns of pancreatic carcinoma patients with that of gastric cancer patients, other pancreatic disease patients, and healthy volunteers. By two-dimensional gel electrophoresis (2-DE) analyses and mass spectroscopic identification, 10 protein spots were found significantly changed in pancreatic carcinoma and 5 proteins including cyclin I, Rab GDP dissociation inhibitor beta (GDI2), alpha-1 antitrypsin precursor, Haptoglobin precursor, and Serotransferrin precursor were successfully identified. The increased levels of cyclin I and GDI2 found to be associated with pancreatic carcinoma were further confirmed by Western blot analyses in an independent series of serum samples and/or pancreatic juice samples. Applying immunohistochemistry, we further validated expression of cyclin I and GDI2 in additional pancreatic carcinomas. These results indicate that cyclin I and GDI2 may be potential molecular targets for pancreatic cancer diagnostics and therapeutics.  (+info)

Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. (3/7)

The cellular pathways of motor neuronal injury have been investigated in the SOD1 G93A murine model of familial amyotrophic lateral sclerosis (ALS) using laser-capture microdissection and microarray analysis. The advantages of this study include the following: analysis of changes specifically in motor neurons (MNs), while still detecting effects of interactions with neighboring cells; the ability to profile changes during disease progression, an approach not possible in human ALS; and the use of transgenic mice bred on a homogeneous genetic background, eliminating the confounding effects arising from a mixed genetic background. By using this rigorous approach, novel changes in key cellular pathways have been detected at both the presymptomatic and late stages, which have been validated by quantitative reverse transcription-PCR. At the presymptomatic stage (60 d), MNs extracted from SOD1 G93A mice show a significant increase in expression of genes subserving both transcriptional and translational functions, as well as lipid and carbohydrate metabolism, mitochondrial preprotein translocation, and respiratory chain function, suggesting activation of a strong cellular adaptive response. Mice 90 d old still show upregulation of genes involved in carbohydrate metabolism, whereas transcription and mRNA processing genes begin to show downregulation. Late in the disease course (120 d), important findings include the following: marked transcriptional repression, with downregulation of multiple transcripts involved in transcriptional and metabolic functions; upregulation of complement system components; and increased expression of key cyclins involved in cell-cycle regulation. The changes described in the motor neuron transcriptome evolving during the disease course highlight potential novel targets for neuroprotective therapeutic intervention.  (+info)

Cyclin I activates Cdk5 and regulates expression of Bcl-2 and Bcl-XL in postmitotic mouse cells. (4/7)


Cyclin I-Cdk5 governs survival in post-mitotic cells. (5/7)

Cdk5 has long been recognized to play an important role in development, maturation and apoptosis of postmitotic and terminally differentiated cells. Activation of Cdk5 is tightly regulated by specific activators. Cyclin I was recently characterized as the first cyclin protein that binds to and activates Cdk5. Cyclin I-Cdk5 activates the MEK-ERK pathway and results in increased Bcl-2 and Bcl-X(L) mRNA and protein levels. Lack of Cyclin I renders podocytes more susceptible to apoptosis. Interestingly, activation of Cdk5 by p35 is also involved in the podocytes' response to injury. In the absence of p35, podocytes are more prone to undergo apoptosis. Here, we propose a new model where Cdk5 plays a central role in the cellular response machinery against injury-induced apoptosis of post-mitotic cells. While Cyclin I-Cdk5 regulates Bcl-2 family proteins through activation of the MEK-ERK pathway, p35-Cdk5 directly phosphorylates and stabilizes Bcl-2.  (+info)

Both cyclin I and p35 are required for maximal survival benefit of cyclin-dependent kinase 5 in kidney podocytes. (6/7)


Cyclin I is involved in the regulation of cell cycle progression. (7/7)


387453381 - EP 0863204 A4 20000119 - HUMAN CYCLIN I AND GENE ENCODING THE SAME - [origin: US6218115B1] This invention relates to a novel protein having a high degree of homology to the amino acid sequence of the so-called cyclin box which is characteristic of cyclins: they are herein referred to as human cyclin I or human cyclin I protein. Further, the invention relates to a gene encoding their amino acid sequences and the protein: the gene is referred to as gene encoding human cyclin I or human cyclin I gene. Also, the invention relates to expression vector into which the human cyclin I gene is incorporated as well as to a transformant into which the vector is introduced. Still further, the invention relates to a recombinant protein obtained by growing the transformant. In addition, the invention relates to a novel neuron-marking method using an anitisense nucleotide of the gene as probe. Furthermore, the invention relates to method for screening cancer cell using the human cyclin I gene.
The i-CDK9-induced increase in CDK9s binding to the MYC locus is mostly BRD4-dependent.DOI:http://dx.doi.org/10.7554/eLife.06535.017
Lou Pagnucco wrote: , the Milan group (I cannot remember the authors) that published , in Nature some months ago, seemed to show that mice genetically , modified to exhibit lower rates of apoptosis lived about 35% longer. Miglaccio et al, Nature 402(6759):309-313. True, but it is crucial to remember that the reduction of apoptosis was not indiscriminate: it was specifically a reduction in oxidative stress-induced apoptosis due to knockout of one isoform of a protein. However, I still agree strongly with you that more experiments are needed. , Could failed, transient, apoptotic episodes result in extensive , cell/tissue damage instead of cell death? ... Is it also possible , that these failed cellular suicide attempts are due to mitochodrial , oxidative bursts that manage to leave behind the biomarkers of cellular , ageing? i.e., Is it possible that normal mitochondrial respiration has , gotten a bum rap and unfairly indicted for the cellular damage seen , in senescent cells? (whereas these ...
2494 Cyclin I (CCNI) is a member of the recently described inhibitory class of cyclin proteins. The other members of this class, cyclins G1 and G2, have been implicated in the induction of cell cycle arrest. Cyclin I is widely expressed in terminally differentiated tissues, but its function remains to be determined. We previously identified cyclin I as antigenic in a mouse model of ovarian cancer. Here, we examined expression of the human cyclin I gene in normal tissues, in tumor cell lines, and in primary human ovarian tumors. By Northern blot analysis, cyclin I was expressed at moderate to high levels in all normal tissues examined, including normal ovary. In contrast, cyclin I mRNA was dramatically reduced in nine of twenty-five ovarian tumor samples examined. These studies were confirmed and extended using quantitative real-time PCR analysis. More than half of the tumors evaluated had very low levels of cyclin I mRNA compared to the expression levels in normal ovarian tissue and other normal ...
They developed an angiogenic microfiber patch that releases angiogenic growth factors along aligned fibers and subsequently directs the spacing and orientation of mature and functional neovessels. The angiogenic microfiber patch was prepared by electrostatically binding electrosprayed angiogenic growth factor-encapsulating polymeric microparticles with electrospun polymeric microfibers. The microparticles released the angiogenic growth factors in a sustained manner, while the straightly aligned polymeric fibers guided cells to adhere along their orientation.. The patch will be highly useful in treating cardiovascular disease, which is the leading cause of death and disability of people all over the world, Kong said.. Their work was reported in Advanced Materials in late July.. ...
TY - JOUR. T1 - Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes. AU - Hishikawa, Akihito. AU - Hayashi, Kaori. AU - Abe, Takaya. AU - Kaneko, Mari. AU - Yokoi, Hideki. AU - Azegami, Tatsuhiko. AU - Nakamura, Mari. AU - Yoshimoto, Norifumi. AU - Kanda, Takeshi. AU - Sakamaki, Yusuke. AU - Itoh, Hiroshi. PY - 2019/1/29. Y1 - 2019/1/29. N2 - Hishikawa et al. reveal that KAT5-mediated DNA repair is essential for podocyte maintenance and is related to changes in DNA methylation status. Decreased podocyte KAT5 expression may contribute to the pathophysiology of diabetic nephropathy, suggesting a therapeutic target.. AB - Hishikawa et al. reveal that KAT5-mediated DNA repair is essential for podocyte maintenance and is related to changes in DNA methylation status. Decreased podocyte KAT5 expression may contribute to the pathophysiology of diabetic nephropathy, suggesting a therapeutic target.. KW - diabetic nephropathy. KW - DNA damage repair. KW - ...
message was truncated but as of note: senescent cells (Hayflick cells) are not necessarily apoptotic. Many post-mitotic cells undergo apoptosis. See all the work on insects by me et al, Truman, Schwartz, Locke, etc. The story of apoptosis as an aborted mitosis derives from lymphocytes and is not necessarily valid, though the signalling mechansisms are interesting. See upcoming meetings at Lake Placid 9/29; Keystone Feb 95, Gordon Conf July 95. Richard A. Lockshin/Dept. Biol. Sci. St. Johns University/8000 Utopia P Jamaica NY 11439 USA/Phone 718: 990-1854/ Fax 718: 380-8543 In article ,35se7t$nru at expert.cc.purdue.edu, ckwen at expert.cc.purdue.edu (Chi-kuang Wen) writes: ,Dear Netter: , Can anyone tell me that if the cells in a mature animal or plant tissue still keep cell-division and cell-death to keep homeostasi ,cell-division and let the cells become senescent? In addition to the inactivation of telemerase may contribute to senescence, is th ,inducing senescence? If most of the cells in ...
Unfortunately, because of the early embryonic lethality associated with Mdm2-null and Mdmx-null mutations, it has been difficult to assess the physiological contributions of Mdm2 and Mdmx to the regulation of p53 levels and activity. However, conditional alleles have recently been developed that yield further insight into how and in what cell types Mdm2 and Mdmx regulate p53 (Grier et al., 2002; Steinman and Jones, 2002; Mendrysa et al., 2003; Grier et al., 2006).. To test whether Mdm2 and Mdmx are required to restrain p53 activity in a single cell type, Xiong et al. conditionally inactivated both Mdm2 and Mdmx in neuronal progenitors (Xiong et al., 2006). Meanwhile, Francoz et al. conditionally expressed p53 in neuronal progenitor cells or in post-mitotic cells of mice lacking Mdm2 and/or Mdmx (Francoz et al., 2006). Loss of Mdmx or Mdm2 leads to distinct phenotypes (see below) but, importantly, all phenotypes disappear in the absence of p53. Both Mdm2 and Mdmx are thus required to inhibit p53 ...
Adult Literacy is co-funded by the Irish Government and the European Social Fund (ESF) as part of the ESF Programme for Employability, Inclusion and Learning 2014-2020. ...
A fourth approach has used gels of tuneable stiffness to alter the mechanical environment of cells (Figure 5). Polyacrylamide gels coated with collagen I have been used to assess podocyte morphology on a range of soft and stiff substrates [26]. The authors found that increased substrate stiffness resulted in more mouse podocyte spreading and an increased differentiation phenotype [26]. Similarly, Abdallah and colleagues cultured human podocytes on hydrolysed polyacrylamide (PAAm) hydrogel substrates and observed dense actin cytoskeleton formation and cell spreading with increased substrate stiffness [27]. These results were similar to a recent study that investigated whether changes in substrate stiffness affect podocyte morphology and whether optimal substrate stiffness drives podocyte differentiation and biochemical specialization. A tuneable substrate composed of gelatin microbial transglutaminase (gelatin-mTG) was used at a stiffness range (0.6-13 kPa) spanning that of healthy and diseased ...
Podoplanin is usually found in human tissues such as kidney podocytes, heart,lung, placenta, skeletal muscle, salivary glands, in myofibroblasts of the breast, mesothelial cell and osteoblasts. It is also upregulated on diverse human cancers like squamous cell carcinoma of the oral cavity,lungs, larynx, esophagus, cervix, skin and in some tumor related of central nervous system. A podoplanin physiological function is not fully determined yet it has been proposed as the marker of lung injury. As it is expressed in lymphatic cells shows a significant role as a specific marker forlymphatic endothelial cells and lymphangiogenesis wherein expression of endothelial cell upholds cell migration, adhesion and tube formation. Gene name: PDPN Protein name: Podoplanin Synonyms: • T1A • T1A2 • GP36 • OTS8 • AGGRUS • Nlrp4g NLR family See also: • Mucin • Transmembrane protein ...
Glomerular visceral epithelial cells, also known as podocytes, are vital to both regular kidney function as well as the development of kidney disease. localization to cell-cell junctions and driven which the SH3 domains of myo1e tail interacts with ZO-1, an element from the slit diaphragm complicated and restricted junctions. These results claim that myo1e represents an element from Docosapentaenoic acid 22n-3 the slit diaphragm complicated and may donate to regulating junctional integrity in kidney podocytes. and (from 2 representative fractionation tests) indicate that myo1e, podocin, and ZO-1 are enriched in the detergent-resistant (DR) slit diaphragm small percentage, whereas another podocyte marker, synaptopodin, exists in the cytoplasmic small percentage. The white series at indicates that 2 split elements of the blot have already been placed next to one another. indicate the locations stained for myo1e just), indicating that myo1e exists in podocyte cell systems not only is ...
Our data revealed that the mode of neurogenesis in onychophorans is more similar to that found in hexapods and crustaceans than that in chelicerates and myriapods as the onychophoran neuroectoderm shows neither post-mitotic cell clusters nor segmental invaginations. In Onychophora, instead, single precursors are recruited for neuronal fate and migrate internally as bottle-like cells, which is similar to the mode found in hexapods (figure 4). These immigrated cells are mitotically active, and in this respect resemble the neuronal stem cells (neuroblasts) of both crustaceans and hexapods (Harzsch 2001; Stollewerk & Simpson 2005; Ungerer & Scholtz 2008), even though they do not show asymmetric cell divisions. Our findings thus suggest that immigration of single cells, followed by their mitotic activity, is an ancestral feature of arthropod neurogenesis, while asymmetric cell divisions are a synapomorphy of crustaceans and hexapods (figure 8). The absence of the following three characters in ...
October 15, 2012 (Toronto, ON) - In a study published in the October issue of the prestigious journal Cell, researchers Drs. Susan Quaggin and Tony Pawson at Mount Sinai Hospitals Samuel Lunenfeld Research Institute, with their teams of post-doctoral researchers, have made an important discovery relating to the effects of a vital signalling protein in the kidney, potentially impacting drug therapies and treatment for the more than 30,000 Canadians who suffer from kidney failure.. The research team uncovered new information about a key binding protein of VEGF (vascular endothelial growth factor) - a protein produced by cells that triggers growth and other changes. Drs. Quaggin and Pawson discovered that FLT1, a protein that acts as one of the targets of VEGF, plays a significant role in the health and development of microscopic kidney filters called glomeruli and is particularly important in kidney podocytes which are specialized cells in the filters, needed for proper urine production. When ...
Purpose: : The Lethal Giant Larvae (Lgl) proteins are demonstrated substrates of atypical Protein Kinase C (aPKC). Previously, we have shown that aPKC lamda and zeta are essential for multiple aspects of retinal development. During zebrafish retinal development, loss of both aPKC isoforms results in retinal defects in mitotic cell behaviors (mitotic division orientation and M-phase localization), post-mitotic cell migration, photoreceptor morphogenesis, and overall retinal histology. The cell type positioning defects are non-cell autonomous, indicating that aPKC activity may function by regulating a secreted signal. Lgl proteins have been shown to regulate polarized exocytosis by interacting with exocytic machinery in both yeast and mammalian cells. To begin to test whether Lgl mediates aPKC functions during retinal development, we have isolated the zebrafish Lgl1 homologue and investigated the expression and loss-of-function consequences of Lgl1 and Lgl2 within the developing retina. Methods: : ...
The terminally differentiated podocyte functions as a critical barrier to prevent proteinuria, and proteinuria is the clinical signature for podocyte injury, with or without loss of renal functions. Emerging experimental and clinical studies have highlighted that loss of podocyte directly causes proteinuria and glomerulosclerosis, owing to podocyte apoptosis or detachment (24-27). The present study demonstrated, to the best of our knowledge for the first time, that kidney and brain associated protein WWC1, is a critical molecular in podocyte injury. Reduced WWC1 expression was identified in injured podocytes, and loss of WWC1 directly induced podocyte apoptosis. In addition further evidence was obtained that WWC1 protected podocytes from apoptosis by preventing SD protein dendrin from relocating into nuclei.. The expression of WWC1 (KIBRA), the mammalian ortholog of Kibra, has been observed to be enriched in kidney and brain (18). In Drosophila, Kibra predominantly acts in the Merlin branch ...
In this Chicken Nation, here are the best restaurant dishes, including a classic wood-oven-roasted chicken, Vietnamese-inspired wings and spicy fried thighs. Here are the best chicken dishes in America, from roasted chicken to spicy fried thighs.

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