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 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.
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 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
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.
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 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.
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.
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.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
A 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.
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 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 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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
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.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
A 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.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.
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.
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.
Agents that inhibit PROTEIN KINASES.
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 cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
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.
An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.
A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.
A cell line derived from cultured tumor cells.
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.
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.
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.
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.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
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.
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.
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.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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.
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
The 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.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
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.
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.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
Transport proteins that carry specific substances in the blood or across cell membranes.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
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 proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
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.
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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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 serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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.
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.
The rate dynamics in chemical or physical systems.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
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.
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 transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
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.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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)
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Elements of limited time intervals, contributing to particular results or situations.
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.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.
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.
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.
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 class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
A group of phenyl benzopyrans named for having structures like FLAVONES.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.
Proteins prepared by recombinant DNA technology.
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.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
The process by which a DNA molecule is duplicated.
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.
Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
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.
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.
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 non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.
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 ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
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.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
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.
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.
Tumors or cancer of the human BREAST.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
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).
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.
A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.
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.

Cyclin C/CDK8 and cyclin H/CDK7/p36 are biochemically distinct CTD kinases. (1/122)

Phosphorylation of the carboxyl-terminal domain (CTD) of RNA polymerase II is important for basal transcriptional processes in vivo and for cell viability. Several kinases, including certain cyclin-dependent kinases, can phosphorylate this substrate in vitro. It has been proposed that differential CTD phosphorylation by different kinases may regulate distinct transcriptional processes. We have found that two of these kinases, cyclin C/CDK8 and cyclin H/CDK7/p36, can specifically phosphorylate distinct residues in recombinant CTD substrates. This difference in specificity may be largely due to their varying ability to phosphorylate lysine-substituted heptapeptide repeats within the CTD, since they phosphorylate the same residue in CTD consensus heptapeptide repeats. Furthermore, this substrate specificity is reflected in vivo where cyclin C/ CDK8 and cyclin H/CDK7/p36 can differentially phosphorylate an endogenous RNA polymerase II substrate. Several small-molecule kinase inhibitors have different specificities for these related kinases, indicating that these enzymes have diverse active-site conformations. These results suggest that cyclin C/CDK8 and cyclin H/CDK7/p36 are physically distinct enzymes that may have unique roles in transcriptional regulation mediated by their phosphorylation of specific sites on RNA polymerase II.  (+info)

GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8. (2/122)

Phosphorylation of the yeast transcription factor GAL4 at S699 is required for efficient galactose-inducible transcription. We demonstrate that this site is a substrate for the RNA polymerase holoenzyme-associated CDK SRB10. S699 phosphorylation requires SRB10 in vivo, and this site is phosphorylated by purified SRB10/ SRB11 CDK/cyclin in vitro. RNA Pol II holoenzymes purified from WT yeast phosphorylate GAL4 at sites observed in vivo whereas holoenzymes from srb10 yeast are incapable of phosphorylating GAL4 at S699. Mutations at GAL4 S699 and srb10 are epistatic for GAL induction, demonstrating that SRB10 regulates GAL4 activity through this phosphorylation in vivo. These results demonstrate a function for the SRB10/ CDK8 holoenzyme-associated CDK that involves regulation of transactivators by phosphorylation during transcriptional activation.  (+info)

Transcription: Common cofactors and cooperative recruitment. (3/122)

Mammalian counterparts of the yeast SRB/MED transcriptional 'mediator' complex have recently been identified. These complexes define a common cofactor requirement for diverse transcriptional activators and underscore the conserved nature of the transcriptional machinery among eukaryotic organisms.  (+info)

Multiple signals regulate GAL transcription in yeast. (4/122)

Gal4p activates transcription of the Saccharomyces GAL genes in response to galactose and is phosphorylated during interaction with the RNA polymerase II (Pol II) holoenzyme. One phosphorylation at S699 is necessary for full GAL induction and is mediated by Srb10p/CDK8 of the RNA Pol II holoenzyme mediator subcomplex. Gal4p S699 phosphorylation is necessary for sensitive response to inducer, and its requirement for GAL induction can be abrogated by high concentrations of galactose in strains expressing wild-type GAL2 and GAL3. Gal4p S699 phosphorylation occurs independently of Gal3p and is responsible for the long-term adaptation response observed in gal3 yeast. SRB10 and GAL3 are shown to represent parallel mechanisms for GAL gene induction. These results demonstrate that Gal4p activity is controlled by two independent signals: one that acts through Gal3p-galactose and a second that is mediated by the holoenzyme-associated cyclin-dependent kinase Srb10p. Since Srb10p is regulated independently of galactose, our results suggest a function for CDK8 in coordinating responses to specific inducers with the environment through the phosphorylation of gene-specific activators.  (+info)

A regulatory shortcut between the Snf1 protein kinase and RNA polymerase II holoenzyme. (5/122)

RNA polymerase II holoenzymes respond to activators and repressors that are regulated by signaling pathways. Here we present evidence for a "shortcut" mechanism in which the Snf1 protein kinase of the glucose signaling pathway directly regulates transcription by the yeast holoenzyme. In response to glucose limitation, the Snf1 kinase stimulates transcription by holoenzyme that has been artificially recruited to a reporter by a LexA fusion to a holoenzyme component. We show that Snf1 interacts physically with the Srb/mediator proteins of the holoenzyme in both two-hybrid and coimmunoprecipitation assays. We also show that a catalytically hyperactive Snf1, when bound to a promoter as a LexA fusion protein, activates transcription in a glucose-regulated manner; moreover, this activation depends on the integrity of the Srb/mediator complex. These results suggest that direct regulatory interactions between signal transduction pathways and RNA polymerase II holoenzyme provide a mechanism for transcriptional control in response to important signals.  (+info)

Genetic analysis of the role of Pol II holoenzyme components in repression by the Cyc8-Tup1 corepressor in yeast. (6/122)

The Cyc8-Tup1 corepressor complex is targeted to promoters by pathway-specific DNA-binding repressors, thereby inhibiting the transcription of specific classes of genes. Genetic screens have identified mutations in a variety of Pol II holoenzyme components (Srb8, Srb9, Srb10, Srb11, Sin4, Rgr1, Rox3, and Hrs1) and in the N-terminal tails of histones H3 and H4 that weaken repression by Cyc8-Tup1. Here, we analyze the effect of individual and multiple mutations in many of these components on transcriptional repression of natural promoters that are regulated by Cyc8-Tup1. In all cases tested, individual mutations have a very modest effect on SUC2 RNA levels and no detectable effect on levels of ANB1, MFA2, and RNR2. Furthermore, multiple mutations within the Srb components, between Srbs and Sin4, and between Srbs and histone tails affect Cyc8-Tup1 repression to the same modest extent as the individual mutations. These results argue that the weak effects of the various mutations on repression by Cyc8-Tup1 are not due to redundancy among components of the Pol II machinery, and they argue against a simple redundancy between the holoenzyme and chromatin pathways. In addition, phenotypic analysis indicates that, although Srbs8-11 are indistinguishable with respect to Cyc8-Tup1 repression, the individual Srbs are functionally distinct in other respects. Genetic interactions among srb mutations imply that a balance between the activities of Srb8 + Srb10 and Srb11 is important for normal cell growth.  (+info)

Roles of transcription factor Mot3 and chromatin in repression of the hypoxic gene ANB1 in yeast. (7/122)

The hypoxic genes of Saccharomyces cerevisiae are repressed by a complex consisting of the aerobically expressed, sequence-specific DNA-binding protein Rox1 and the Tup1-Ssn6 general repressors. The regulatory region of one well-studied hypoxic gene, ANB1, is comprised of two operators, OpA and OpB, each of which has two strong Rox1 binding sites, yet OpA represses transcription almost 10 times more effectively than OpB. We show here that this difference is due to the presence of a Mot3 binding site in OpA. Mutations in this site reduced OpA repression to OpB levels, and the addition of a Mot3 binding site to OpB enhanced repression. Deletion of the mot3 gene also resulted in reduced repression of ANB1. Repression of two other hypoxic genes in which Mot3 sites were associated with Rox1 sites was reduced in the deletion strain, but other hypoxic genes were unaffected. In addition, the mot3Delta mutation caused a partial derepression of the Mig1-Tup1-Ssn6-repressed SUC2 gene, but not the alpha2-Mcm1-Tup1-Ssn6-repressed STE2 gene. The Mot3 protein was demonstrated to bind to the ANB1 OpA in vitro. Competition experiments indicated that there was no interaction between Rox1 and Mot3, indicating that Mot3 functions either in Tup1-Ssn6 recruitment or directly in repression. A great deal of evidence has accumulated suggesting that the Tup1-Ssn6 complex represses transcription through both nucleosome positioning and a direct interaction with the basal transcriptional machinery. We demonstrate here that under repressed conditions a nucleosome is positioned over the TATA box in the wild-type ANB1 promoter. This nucleosome was absent in cells carrying a rox1, tup1, or mot3 deletion, all of which cause some degree of derepression. Interestingly, however, this positioned nucleosome was also lost in a cell carrying a deletion of the N-terminal coding region of histone H4, yet ANB1 expression remained fully repressed. A similar deletion in the gene for histone H3, which had no effect on repression, had only a minor effect on the positioned nucleosome. These results indicate that the nucleosome phasing on the ANB1 promoter caused by the Rox1-Mot3-Tup1-Ssn6 complex is either completely redundant with a chromatin-independent repression mechanism or, less likely, plays no role in repression at all.  (+info)

Characterization of CAF4 and CAF16 reveals a functional connection between the CCR4-NOT complex and a subset of SRB proteins of the RNA polymerase II holoenzyme. (8/122)

The CCR4-NOT transcriptional regulatory complex affects transcription both positively and negatively and consists of the following two complexes: a core 1 x 10(6) dalton (1 MDa) complex consisting of CCR4, CAF1, and the five NOT proteins and a larger, less defined 1.9-MDa complex. We report here the identification of two new factors that associate with the CCR4-NOT proteins as follows: CAF4, a WD40-containing protein, and CAF16, a putative ABC ATPase. Whereas neither CAF4 nor CAF16 was part of the core CCR4-NOT complex, both CAF16 and CAF4 appeared to be present in the 1.9-MDa complex. CAF4 also displayed physical interactions with multiple CCR4-NOT components and with DBF2, a likely component of the 1.9-MDa complex. In addition, both CAF4 and CAF16 were found to interact in a CCR4-dependent manner with SRB9, a component of the SRB complex that is part of the yeast RNA polymerase II holoenzyme. The three related SRB proteins, SRB9, SRB10, and SRB11, were found to interact with and to coimmunoprecipitate DBF2, CAF4, CCR4, NOT2, and NOT1. Defects in SRB9 and SRB10 also affected processes at the ADH2 locus known to be controlled by components of the CCR4-NOT complex; an srb9 mutation was shown to reduce ADH2 derepression and either an srb9 or srb10 allele suppressed spt10-enhanced expression of ADH2. In addition, srb9 and srb10 alleles increased ADR1(c)-dependent ADH2 expression; not4 and not5 deletions are the only other known defects that elicit this phenotype. These results suggest a close physical and functional association between components of the CCR4-NOT complexes and the SRB9, -10, and -11 components of the holoenzyme.  (+info)

There are different types of Breast Neoplasms such as:

1. Fibroadenomas: These are benign tumors that are made up of glandular and fibrous tissues. They are usually small and round, with a smooth surface, and can be moved easily under the skin.

2. Cysts: These are fluid-filled sacs that can develop in both breast tissue and milk ducts. They are usually benign and can disappear on their own or be drained surgically.

3. Ductal Carcinoma In Situ (DCIS): This is a precancerous condition where abnormal cells grow inside the milk ducts. If left untreated, it can progress to invasive breast cancer.

4. Invasive Ductal Carcinoma (IDC): This is the most common type of breast cancer and starts in the milk ducts but grows out of them and invades surrounding tissue.

5. Invasive Lobular Carcinoma (ILC): It originates in the milk-producing glands (lobules) and grows out of them, invading nearby tissue.

Breast Neoplasms can cause various symptoms such as a lump or thickening in the breast or underarm area, skin changes like redness or dimpling, change in size or shape of one or both breasts, discharge from the nipple, and changes in the texture or color of the skin.

Treatment options for Breast Neoplasms may include surgery such as lumpectomy, mastectomy, or breast-conserving surgery, radiation therapy which uses high-energy beams to kill cancer cells, chemotherapy using drugs to kill cancer cells, targeted therapy which uses drugs or other substances to identify and attack cancer cells while minimizing harm to normal cells, hormone therapy, immunotherapy, and clinical trials.

It is important to note that not all Breast Neoplasms are cancerous; some are benign (non-cancerous) tumors that do not spread or grow.

Explanation: Neoplastic cell transformation is a complex process that involves multiple steps and can occur as a result of genetic mutations, environmental factors, or a combination of both. The process typically begins with a series of subtle changes in the DNA of individual cells, which can lead to the loss of normal cellular functions and the acquisition of abnormal growth and reproduction patterns.

Over time, these transformed cells can accumulate further mutations that allow them to survive and proliferate despite adverse conditions. As the transformed cells continue to divide and grow, they can eventually form a tumor, which is a mass of abnormal cells that can invade and damage surrounding tissues.

In some cases, cancer cells can also break away from the primary tumor and travel through the bloodstream or lymphatic system to other parts of the body, where they can establish new tumors. This process, known as metastasis, is a major cause of death in many types of cancer.

It's worth noting that not all transformed cells will become cancerous. Some forms of cellular transformation, such as those that occur during embryonic development or tissue regeneration, are normal and necessary for the proper functioning of the body. However, when these transformations occur in adult tissues, they can be a sign of cancer.

See also: Cancer, Tumor

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1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.

2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.

3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.

4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.

5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.

6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.

7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.

8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.

9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.

10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.

Neoplasm refers to an abnormal growth of cells that can be benign (non-cancerous) or malignant (cancerous). Neoplasms can occur in any part of the body and can affect various organs and tissues. The term "neoplasm" is often used interchangeably with "tumor," but while all tumors are neoplasms, not all neoplasms are tumors.

Types of Neoplasms

There are many different types of neoplasms, including:

1. Carcinomas: These are malignant tumors that arise in the epithelial cells lining organs and glands. Examples include breast cancer, lung cancer, and colon cancer.
2. Sarcomas: These are malignant tumors that arise in connective tissue, such as bone, cartilage, and fat. Examples include osteosarcoma (bone cancer) and soft tissue sarcoma.
3. Lymphomas: These are cancers of the immune system, specifically affecting the lymph nodes and other lymphoid tissues. Examples include Hodgkin lymphoma and non-Hodgkin lymphoma.
4. Leukemias: These are cancers of the blood and bone marrow that affect the white blood cells. Examples include acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL).
5. Melanomas: These are malignant tumors that arise in the pigment-producing cells called melanocytes. Examples include skin melanoma and eye melanoma.

Causes and Risk Factors of Neoplasms

The exact causes of neoplasms are not fully understood, but there are several known risk factors that can increase the likelihood of developing a neoplasm. These include:

1. Genetic predisposition: Some people may be born with genetic mutations that increase their risk of developing certain types of neoplasms.
2. Environmental factors: Exposure to certain environmental toxins, such as radiation and certain chemicals, can increase the risk of developing a neoplasm.
3. Infection: Some neoplasms are caused by viruses or bacteria. For example, human papillomavirus (HPV) is a common cause of cervical cancer.
4. Lifestyle factors: Factors such as smoking, excessive alcohol consumption, and a poor diet can increase the risk of developing certain types of neoplasms.
5. Family history: A person's risk of developing a neoplasm may be higher if they have a family history of the condition.

Signs and Symptoms of Neoplasms

The signs and symptoms of neoplasms can vary depending on the type of cancer and where it is located in the body. Some common signs and symptoms include:

1. Unusual lumps or swelling
2. Pain
3. Fatigue
4. Weight loss
5. Change in bowel or bladder habits
6. Unexplained bleeding
7. Coughing up blood
8. Hoarseness or a persistent cough
9. Changes in appetite or digestion
10. Skin changes, such as a new mole or a change in the size or color of an existing mole.

Diagnosis and Treatment of Neoplasms

The diagnosis of a neoplasm usually involves a combination of physical examination, imaging tests (such as X-rays, CT scans, or MRI scans), and biopsy. A biopsy involves removing a small sample of tissue from the suspected tumor and examining it under a microscope for cancer cells.

The treatment of neoplasms depends on the type, size, location, and stage of the cancer, as well as the patient's overall health. Some common treatments include:

1. Surgery: Removing the tumor and surrounding tissue can be an effective way to treat many types of cancer.
2. Chemotherapy: Using drugs to kill cancer cells can be effective for some types of cancer, especially if the cancer has spread to other parts of the body.
3. Radiation therapy: Using high-energy radiation to kill cancer cells can be effective for some types of cancer, especially if the cancer is located in a specific area of the body.
4. Immunotherapy: Boosting the body's immune system to fight cancer can be an effective treatment for some types of cancer.
5. Targeted therapy: Using drugs or other substances to target specific molecules on cancer cells can be an effective treatment for some types of cancer.

Prevention of Neoplasms

While it is not always possible to prevent neoplasms, there are several steps that can reduce the risk of developing cancer. These include:

1. Avoiding exposure to known carcinogens (such as tobacco smoke and radiation)
2. Maintaining a healthy diet and lifestyle
3. Getting regular exercise
4. Not smoking or using tobacco products
5. Limiting alcohol consumption
6. Getting vaccinated against certain viruses that are associated with cancer (such as human papillomavirus, or HPV)
7. Participating in screening programs for early detection of cancer (such as mammograms for breast cancer and colonoscopies for colon cancer)
8. Avoiding excessive exposure to sunlight and using protective measures such as sunscreen and hats to prevent skin cancer.

It's important to note that not all cancers can be prevented, and some may be caused by factors that are not yet understood or cannot be controlled. However, by taking these steps, individuals can reduce their risk of developing cancer and improve their overall health and well-being.

There are several types of lung neoplasms, including:

1. Adenocarcinoma: This is the most common type of lung cancer, accounting for approximately 40% of all lung cancers. It is a malignant tumor that originates in the glands of the respiratory tract and can be found in any part of the lung.
2. Squamous cell carcinoma: This type of lung cancer accounts for approximately 25% of all lung cancers and is more common in men than women. It is a malignant tumor that originates in the squamous cells lining the airways of the lungs.
3. Small cell lung cancer (SCLC): This is a highly aggressive form of lung cancer that accounts for approximately 15% of all lung cancers. It is often found in the central parts of the lungs and can spread quickly to other parts of the body.
4. Large cell carcinoma: This is a rare type of lung cancer that accounts for only about 5% of all lung cancers. It is a malignant tumor that originates in the large cells of the respiratory tract and can be found in any part of the lung.
5. Bronchioalveolar carcinoma (BAC): This is a rare type of lung cancer that originates in the cells lining the airways and alveoli of the lungs. It is more common in women than men and tends to affect older individuals.
6. Lymphangioleiomyomatosis (LAM): This is a rare, progressive, and often fatal lung disease that primarily affects women of childbearing age. It is characterized by the growth of smooth muscle-like cells in the lungs and can lead to cysts, lung collapse, and respiratory failure.
7. Hamartoma: This is a benign tumor that originates in the tissue of the lungs and is usually found in children. It is characterized by an overgrowth of normal lung tissue and can be treated with surgery.
8. Secondary lung cancer: This type of cancer occurs when cancer cells from another part of the body spread to the lungs through the bloodstream or lymphatic system. It is more common in people who have a history of smoking or exposure to other carcinogens.
9. Metastatic cancer: This type of cancer occurs when cancer cells from another part of the body spread to the lungs through the bloodstream or lymphatic system. It is more common in people who have a history of smoking or exposure to other carcinogens.
10. Mesothelioma: This is a rare and aggressive form of cancer that originates in the lining of the lungs or abdomen. It is caused by asbestos exposure and can be treated with surgery, chemotherapy, and radiation therapy.

Lung diseases can also be classified based on their cause, such as:

1. Infectious diseases: These are caused by bacteria, viruses, or other microorganisms and can include pneumonia, tuberculosis, and bronchitis.
2. Autoimmune diseases: These are caused by an overactive immune system and can include conditions such as sarcoidosis and idiopathic pulmonary fibrosis.
3. Genetic diseases: These are caused by inherited mutations in genes that affect the lungs and can include cystic fibrosis and primary ciliary dyskinesia.
4. Environmental diseases: These are caused by exposure to harmful substances such as tobacco smoke, air pollution, and asbestos.
5. Radiological diseases: These are caused by exposure to ionizing radiation and can include conditions such as radiographic breast cancer and lung cancer.
6. Vascular diseases: These are caused by problems with the blood vessels in the lungs and can include conditions such as pulmonary embolism and pulmonary hypertension.
7. Tumors: These can be benign or malignant and can include conditions such as lung metastases and lung cancer.
8. Trauma: This can include injuries to the chest or lungs caused by accidents or other forms of trauma.
9. Congenital diseases: These are present at birth and can include conditions such as bronchopulmonary foregut malformations and congenital cystic adenomatoid malformation.

Each type of lung disease has its own set of symptoms, diagnosis, and treatment options. It is important to seek medical attention if you experience any persistent or severe respiratory symptoms, as early diagnosis and treatment can improve outcomes and quality of life.

The prognosis for mantle-cell lymphoma is generally poor, with a five-year survival rate of approximately 40%. Treatment options include chemotherapy, immunotherapy, and autologous stem-cell transplantation. The disease often recurs after initial therapy, and subsequent treatments may be less effective.

Mantle-cell lymphoma can be difficult to distinguish from other types of non-Hodgkin lymphoma, such as follicular lymphoma or diffuse large B-cell lymphoma, and a correct diagnosis is important for determining appropriate treatment.

Slide: Mantle Cell Lymphoma (Image courtesy of Nephron/Wikimedia Commons)

1. Tumor size and location: Larger tumors that have spread to nearby tissues or organs are generally considered more invasive than smaller tumors that are confined to the original site.
2. Cellular growth patterns: The way in which cancer cells grow and divide can also contribute to the overall invasiveness of a neoplasm. For example, cells that grow in a disorganized or chaotic manner may be more likely to invade surrounding tissues.
3. Mitotic index: The mitotic index is a measure of how quickly the cancer cells are dividing. A higher mitotic index is generally associated with more aggressive and invasive cancers.
4. Necrosis: Necrosis, or the death of cells, can be an indication of the level of invasiveness of a neoplasm. The presence of significant necrosis in a tumor is often a sign that the cancer has invaded surrounding tissues and organs.
5. Lymphovascular invasion: Cancer cells that have invaded lymphatic vessels or blood vessels are considered more invasive than those that have not.
6. Perineural invasion: Cancer cells that have invaded nerve fibers are also considered more invasive.
7. Histological grade: The histological grade of a neoplasm is a measure of how abnormal the cancer cells look under a microscope. Higher-grade cancers are generally considered more aggressive and invasive than lower-grade cancers.
8. Immunohistochemical markers: Certain immunohistochemical markers, such as Ki-67, can be used to evaluate the proliferative activity of cancer cells. Higher levels of these markers are generally associated with more aggressive and invasive cancers.

Overall, the degree of neoplasm invasiveness is an important factor in determining the likelihood of the cancer spreading to other parts of the body (metastasizing) and in determining the appropriate treatment strategy for the patient.

There are several types of colonic neoplasms, including:

1. Adenomas: These are benign growths that are usually precursors to colorectal cancer.
2. Carcinomas: These are malignant tumors that arise from the epithelial lining of the colon.
3. Sarcomas: These are rare malignant tumors that arise from the connective tissue of the colon.
4. Lymphomas: These are cancers of the immune system that can affect the colon.

Colonic neoplasms can cause a variety of symptoms, including bleeding, abdominal pain, and changes in bowel habits. They are often diagnosed through a combination of medical imaging tests (such as colonoscopy or CT scan) and biopsy. Treatment for colonic neoplasms depends on the type and stage of the tumor, and may include surgery, chemotherapy, and/or radiation therapy.

Overall, colonic neoplasms are a common condition that can have serious consequences if left untreated. It is important for individuals to be aware of their risk factors and to undergo regular screening for colon cancer to help detect and treat any abnormal growths or tumors in the colon.

Malignant prostatic neoplasms are cancerous tumors that can be aggressive and spread to other parts of the body (metastasize). The most common type of malignant prostatic neoplasm is adenocarcinoma of the prostate, which accounts for approximately 95% of all prostate cancers. Other types of malignant prostatic neoplasms include sarcomas and small cell carcinomas.

Prostatic neoplasms can be diagnosed through a variety of tests such as digital rectal examination (DRE), prostate-specific antigen (PSA) test, imaging studies (ultrasound, CT scan or MRI), and biopsy. Treatment options for prostatic neoplasms depend on the type, stage, and grade of the tumor, as well as the patient's age and overall health. Treatment options can include active surveillance, surgery (robotic-assisted laparoscopic prostatectomy or open prostatectomy), radiation therapy (external beam radiation therapy or brachytherapy), and hormone therapy.

In summary, Prostatic Neoplasms are tumors that occur in the prostate gland, which can be benign or malignant. The most common types of malignant prostatic neoplasms are adenocarcinoma of the prostate, and other types include sarcomas and small cell carcinomas. Diagnosis is done through a variety of tests, and treatment options depend on the type, stage, and grade of the tumor, as well as the patient's age and overall health.

SCC typically appears as a firm, flat, or raised bump on the skin, and may be pink, red, or scaly. The cancer cells are usually well-differentiated, meaning they resemble normal squamous cells, but they can grow rapidly and invade surrounding tissues if left untreated.

SCC is more common in fair-skinned individuals and those who spend a lot of time in the sun, as UV radiation can damage the skin cells and increase the risk of cancer. The cancer can also spread to other parts of the body, such as lymph nodes or organs, and can be life-threatening if not treated promptly and effectively.

Treatment for SCC usually involves surgery to remove the cancerous tissue, and may also include radiation therapy or chemotherapy to kill any remaining cancer cells. Early detection and treatment are important to improve outcomes for patients with SCC.

Adenocarcinoma is a term used to describe a variety of different types of cancer that arise in glandular tissue, including:

1. Colorectal adenocarcinoma (cancer of the colon or rectum)
2. Breast adenocarcinoma (cancer of the breast)
3. Prostate adenocarcinoma (cancer of the prostate gland)
4. Pancreatic adenocarcinoma (cancer of the pancreas)
5. Lung adenocarcinoma (cancer of the lung)
6. Thyroid adenocarcinoma (cancer of the thyroid gland)
7. Skin adenocarcinoma (cancer of the skin)

The symptoms of adenocarcinoma depend on the location of the cancer and can include:

1. Blood in the stool or urine
2. Abdominal pain or discomfort
3. Changes in bowel habits
4. Unusual vaginal bleeding (in the case of endometrial adenocarcinoma)
5. A lump or thickening in the breast or elsewhere
6. Weight loss
7. Fatigue
8. Coughing up blood (in the case of lung adenocarcinoma)

The diagnosis of adenocarcinoma is typically made through a combination of imaging tests, such as CT scans, MRI scans, and PET scans, and a biopsy, which involves removing a sample of tissue from the affected area and examining it under a microscope for cancer cells.

Treatment options for adenocarcinoma depend on the location of the cancer and can include:

1. Surgery to remove the tumor
2. Chemotherapy, which involves using drugs to kill cancer cells
3. Radiation therapy, which involves using high-energy X-rays or other particles to kill cancer cells
4. Targeted therapy, which involves using drugs that target specific molecules on cancer cells to kill them
5. Immunotherapy, which involves using drugs that stimulate the immune system to fight cancer cells.

The prognosis for adenocarcinoma is generally good if the cancer is detected and treated early, but it can be more challenging to treat if the cancer has spread to other parts of the body.

The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8". Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ... Cyclin-dependent kinase 8 has been shown to interact with: CCNC CREB binding protein CRSP3 MED1 MED12 MED14 MED16 MED17 MED21 ... Tassan JP, Jaquenoud M, Léopold P, Schultz SJ, Nigg EA (Sep 1995). "Identification of human cyclin-dependent kinase 8, a ...
"Entrez Gene: CDK4 cyclin-dependent kinase 4". "CDK4 - Cyclin-dependent kinase 4 - Homo sapiens (Human) - CDK4 gene & protein". ... "The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ... Kato JY; Matsuoka M; Strom DK; Sherr CJ (1994). "Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase". ...
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It was determined that he RV-cyclin bound to cyclin-dependent kinase 8 (CDK8) and increased its activity. The genes IEGs are ... Birkenheuer, C; Brewster, C; Quackenbush, S; Rovnak, J (2015). "Retroviral Cyclin Controls Cyclin-Dependent Kinase 8-Mediated ... "The retroviral cyclin of walleye dermal sarcoma virus binds cyclin-dependent kinases 3 and 8". Virology. 409 (2): 299-307. doi: ... The retroviral cyclin of walleye dermal sarcoma virus binds cylin-dependent kinases 3 and 8. Transgenic expression of walleye ...
... has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ... CDK2 cyclin-dependent kinase 2". Echalier A, Endicott JA, Noble ME (March 2010). "Recent developments in cyclin-dependent ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ... The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein ...
CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... cyclin A, cyclin B CDK2; cyclin A, cyclin E CDK3; cyclin C CDK4; cyclin D1, cyclin D2, cyclin D3 CDK5; CDK5R1, CDK5R2. See also ... A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell ...
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... like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate ... Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that ... De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (June 1993). "Crystal structure of cyclin-dependent kinase 2 ... Overview of all the structural information available in the PDB for UniProt: P06493 (Cyclin-dependent kinase 1) at the PDBe-KB ...
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Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... 2003). "Expression of Cyclin-Dependent Kinase 6, but Not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse ... "Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. The ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Patel H, Abduljabbar R, Lai ...
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... or CDK9 is a cyclin-dependent kinase associated with P-TEFb. The protein encoded by this gene is a ... Cyclin-Dependent+Kinase+9 at the US National Library of Medicine Medical Subject Headings (MeSH) Drosophila Cyclin dependent ... "Entrez Gene: CDK9 cyclin-dependent kinase 9 (CDC2-related kinase)". MacLachlan TK, Sang N, De Luca A, Puri PL, Levrero M, ... Singh R, Bhardwaj VK, Das P, Purohit R (November 2019). "Natural analogues inhibiting selective cyclin-dependent kinase protein ...
... is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator ... Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C ... "Entrez Gene: CDKN1C cyclin-dependent kinase inhibitor 1C (p57, Kip2)". Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, ... Cyclin-dependent kinase inhibitor 1C has been shown to interact with: LIMK1, MYBL2, MyoD, and PCNA. ENSG00000129757 GRCh38: ...
... cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin. Once cyclin-dependent kinases bind to cyclin, the formed ... Cyclin Cyclin-dependent kinase Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci. 2005 Nov;30(11 ... Yu DS, Zhao R, Hsu EL, Cayer J, Ye F, Guo Y, Shyr Y, Cortez D. Cyclin-dependent kinase 9-cyclin K functions in the replication ... A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic ...
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... is a protein that in humans is encoded by the CDKL1 gene. This gene product is a member of a ... "Entrez Gene: Cyclin dependent kinase like 1". Retrieved 2016-06-07. Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). " ... 16 (7-8): 247-53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614. v t e This article incorporates text from the ... large family of CDC2-related serine/threonine protein kinases. It accumulates primarily in the nucleus. Two transcript variants ...
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... has been shown to interact with Thyroid hormone receptor alpha, Estrogen receptor alpha and Cyclin-dependent kinase 8. ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. Bibcode: ... 277 (45): 42852-8. doi:10.1074/jbc.M206061200. PMID 12218053. Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation ...
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Activation loop Autophosphorylation Ca2+/calmodulin-dependent protein kinase Cell signaling Cyclin-dependent kinase G protein- ... the JAK kinases (a family of protein tyrosine kinases), and the PIP3-dependent kinase cascade were discovered. Kinases are ... Cyclin dependent kinases (CDKs) are a group of several different kinases involved in regulation of the cell cycle. They ... Canavese M, Santo L, Raje N (May 2012). "Cyclin dependent kinases in cancer: potential for therapeutic intervention". Cancer ...
... has been shown to interact with PPARGC1A, Estrogen receptor alpha, STAT2, Cyclin-dependent kinase 8, Glucocorticoid ... 1999). "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. ... Malik, Sohail; Wallberg Annika E; Kang Yun Kyoung; Roeder Robert G (Aug 2002). "TRAP/SMCC/mediator-dependent transcriptional ... Malik S, Wallberg AE, Kang YK, Roeder RG (2002). "TRAP/SMCC/mediator-dependent transcriptional activation from DNA and ...
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Cyclin-dependent kinase 8 Estrogen receptor alpha, Gli3, G9a, PPARGC1A, MED26, SOX9, and Thyroid hormone receptor alpha. GRCh38 ... Zhou H, Kim S, Ishii S, Boyer TG (Dec 2006). "Mediator modulates Gli3-dependent Sonic hedgehog signaling". Molecular and ... "Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex". Nature. 398 (6730): 824-8. Bibcode: ... "MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling". Proceedings ...
... has been shown to interact with: Androgen receptor, BRCA1, Calcitriol receptor, Cyclin-dependent kinase 8, Estrogen ... Lee JW, Choi HS, Gyuris J, Brent R, Moore DD (1995). "Two classes of proteins dependent on either the presence or absence of ... Malik S, Wallberg AE, Kang YK, Roeder RG (August 2002). "TRAP/SMCC/mediator-dependent transcriptional activation from DNA and ... Frade R, Balbo M, Barel M (2002). "RB18A regulates p53-dependent apoptosis". Oncogene. 21 (6): 861-6. doi:10.1038/sj.onc. ...
... has been shown to interact with: ARID1A, BAZ1B, BRCA1, CREB-binding protein, Cyclin-dependent kinase 8, Myc, P53, ... SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a protein that in humans is ... Zhao K, Wang W, Rando OJ, Xue Y, Swiderek K, Kuo A, Crabtree GR (November 1998). "Rapid and phosphoinositol-dependent binding ... Craig E, Zhang ZK, Davies KP, Kalpana GV (January 2002). "A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: ...
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The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the ... ISBN 978-1-58829-500-2.[page needed] Gartel AL, Tyner AL (June 2002). "The role of the cyclin-dependent kinase inhibitor p21 in ... cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes. The SOS response is the ... In one of the earliest steps, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on ...
Biochemical triggers known as cyclin-dependent kinases (Cdks) switch on cell cycles events at the corrected time and in the ... During G1 phase, the G1/S cyclin activity rises significantly near the end of the G1 phase. Complexes of cyclin that are active ... which targets and degrades S and M cyclins (but not G1/S cyclins); and a high concentration of Cdk inhibitors is found during ... At the G1/S checkpoint, formation of the G1/S cyclin with Cdk to form a complex commits the cell to a new division cycle. These ...
Zhu D, Dix DJ, Eddy EM (August 1997). "HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes". ... as CDC2 in unable to form the required heterodimer with cyclin B1 for the meiotic cell cycle to progress beyond S phase. ... and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599 ... where it is necessary for the formation of the complex between CDC2 and cyclin B1. It later becomes incorporated into the ...
... has also been shown to directly inhibits CDK6 (Cyclin-dependent kinase 6) expression and decreases the level of ... Voltage-dependent L-type calcium channel subunit beta-2), TSSK6 (Testis-Specific Serine Kinase 6), NT5DC2 (Cytosolic 5'- ... It was observed that miR-137 expression is lost in Ras-dependent pancreatic cancer, and that restoration of its expression ... Serine/threonine-protein kinase D3). Neault et al. recently identified miR-137 as a senescence effector miRNA induced by ...
Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the ... cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which ... Nigg EA (June 1995). "Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle". BioEssays. 17 (6): 471-80 ... October 2003). "Targets of the cyclin-dependent kinase Cdk1". Nature. 425 (6960): 859-64. Bibcode:2003Natur.425..859U. doi: ...
... but their genetic information cannot be organized and separated into chromosomes due to inhibition of cyclin-dependent kinase ... 139 (8): 1381-90. doi:10.1242/dev.070052. PMC 3308176. PMID 22378638. Edgar BA, Zielke N, Gutierrez C (March 2014). "Endocycles ...
15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby ... DP2 and DP1 are G protein-coupled receptors, with the DP2 receptor coupled to Gi alpha subunit-dependent depression of cellular ... Cyclin D1, Cdk4, and Insulin-like growth factor 1; and e) regulating agents such as HSP70, GPR78, Gadd153, Ubiquitin B, and ... It (they) regulates signaling by: a) inhibiting the STAT3-Janus kinase pathway to block cellular pro-inflammatory responses; b ...
"The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... p21 p53 Cyclin-dependent kinase Cyclin D GRCh38: Ensembl release 89: ENSG00000147889 - Ensembl, May 2017 GRCm38: Ensembl ... "Entrez Gene: CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". Nobori T, Miura K, Wu DJ, Lois A, ... p16 is an inhibitor of cyclin-dependent kinases (CDK). It slows down the cell cycle by prohibiting progression from G1 phase to ...
7SK associates with and inhibits the cyclin dependent kinase activity of P-TEFb through the action of the RNA binding proteins ... Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (October 2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA ... Yang Z, Zhu Q, Luo K, Zhou Q (November 2001). "The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control ... July 2003). "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Molecular and ...
"Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase". Molecular and Cellular Biology. 23 (5): 1764 ... For example, Hsc70 regulates the nuclear accumulation of cyclin D1, which is a key player in G1 to S phase cell cycle ... Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- ... Heat shock 70 kDa protein 8 also known as heat shock cognate 71 kDa protein or Hsc70 or Hsp73 is a heat shock protein that in ...
Hennigan RF, Stambrook PJ (August 2001). "Dominant negative c-jun inhibits activation of the cyclin D1 and cyclin E kinase ... AP-1 functions are heavily dependent on the specific Fos and Jun subunits contributing to AP-1 dimers. The outcome of AP-1 ... Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". The ... Manicassamy S, Gupta S, Huang Z, Sun Z (June 2006). "Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up ...
... phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other ... Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2)". J. Biol. Chem. 276 (49): 45780-90. doi: ... attachment region upstream of the T cell receptor beta gene enhancer binds Cux/CDP and SATB1 and modulates enhancer-dependent ... phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting enzyme, ...
Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature. ... the pre-replication complex only occurs during late M phase and early G1 phase of the cell cycle when cyclin-dependent kinase ( ... The singular archaeal ORC protein recognizes the AT-rich tracts and binds DNA in an ATP-dependent fashion. Eukaryotes typically ... "DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1". EMBO Reports. 7 (11): 1134- ...
It, combined with the Ras pathway, downregulate cyclin D1, a cyclin-dependent kinase, if they are not stimulated by the ... The overexpression of kinase activity in these cells aids in their proliferation. These are known as hormone-dependent breast ... In the presence of mitogens, sufficient cyclin D1 can be produced. This process cascades onwards, producing other cyclins which ... The protein kinase domain found on mitogenic receptors is often hyperactivated in cancer cells, remaining turned on even in the ...
"Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". ... 5 (1): 8. doi:10.1186/1471-2164-5-8. PMC 343271. PMID 14728724. Namciu SJ, Friedman RD, Marsden MD, Sarausad LM, Jasoni CL, ... 34 (Database issue): D415-8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901. Fjaerli HO, Bukholm G, Krog A, Skjaeret C, ...
Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... Simone C, Giordano A (2007). "Abrogation of signal-dependent activation of the cdk9/cyclin T2a complex in human RD ... This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb ... "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 23 (14): 4859-69 ...
... using cyclins and other proteins. As TFIIB has a similar structure to cyclin A it has been suggested that depleted levels of ... It has been suggested that the general transcription factor TFIIH could act as the kinase for this phosphorylation although ... "New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor ... This is thought to be due to similarity TFIIB has to cyclin A. In order to undergo replication, viruses often stop host cells ...
... in which 3 paralogues of subunits of the cyclin-dependent kinase module have evolved by 3 independent gene duplication events ... Xu W, Ji JY (2011). "Dysregulation of CDK8 and Cyclin C in tumorigenesis". J Genet Genomics. 38 (10): 439-52. doi:10.1016/j.jgg ... Mediator can be divided into 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module. Mediator ... Clark AD, Oldenbroek M, Boyer TG (2015). "Mediator kinase module and human tumorigenesis". Crit Rev Biochem Mol Biol. 50 (5): ...
... a well-studied cyclin-dependent protein kinase. Cdc14 antagonizes Cdk1 by stimulating proteolysis of its cyclin partner (cyclin ... It is possible that Cdc14 acts as a phosphatase on all Clb-Cdk1 targets, acting to reverse the effects of the mitotic cyclins. ... April 1999). "Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT ... Furthermore, Cdc14 dephosphorylates the stoichiometric inhibitor of the mitotic cyclins, Sic1, stabilizing Sic1 protein. Cdc14 ...
... cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II ... cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II ... Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene. The protein encoded by this ... "Entrez Gene: CDK5R2 cyclin-dependent kinase 5, regulatory subunit 2 (p39)". Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai ...
TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a ... c-Jun N-terminal kinase (JNK) is a MAP kinase activated by extracellular stress signals such as gamma-radiation, ultraviolet ... EVI1 does not bind other MAP kinases such as p38 or ERK. Among the many other observed defects, EVI1−/− mouse embryos have been ... Together, these two systems disrupt tyrosine kinase signaling and hematopoietic gene transcription. Despite the extensively ...
... it travels to the nucleus via phosphorylation at the Thr-108 position via the mitogenic cyclin dependent kinase (CDK2).[ ... interacts with kinases including serine/threonine protein kinase (PKR). Further studies will need to be performed to better ... E4orf4 partners mainly with protein phosphatase 2A (PP2A) and Src kinases to induce cell death. Modeling of this protein ... This includes presence of cytoplasmic vacuoles, double-membrane vesicles, and a dose-dependent decrease in ATP levels. Melanoma ...
SKP2 targets p27Kip-1, an inhibitor of cyclin-dependent kinases (CDKs). CDKs2/4 partner with the cyclins E/D, respectively, ... This is achieved by continuous control of cyclins or CDKs levels through ubiquitination and degradation. When cyclin E is ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. ... Moreover, ubiquitination can also act to turn on/off the kinase activity of a protein. The critical role of phosphorylation is ...
"Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis". Nature. 560 (7717): 192-197. Bibcode:2018Natur.560.. ... 12 (8): 1228-31. doi:10.1006/cyto.2000.0694. PMID 10930301. Kemp K, Kemp M, Kharazmi A, et al. (1999). "Leishmania-specific T ... 91 (4): 1664-8. doi:10.1172/JCI116372. PMC 288142. PMID 8097208. Ghalib H, Piuvezam M, Skeiky Y, et al. (1993). "Interleukin-10 ... 178 (8): 5383-89. doi:10.4049/jimmunol.178.8.5383. PMID 17404324. Jean, Francois (1995). "Sudan: Speak no Evil, Do no Good". ...
"Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-dependent kinase inhibitors". J. ... Alvocidib (INN; also known as flavopiridol) is a flavonoid alkaloid CDK9 kinase inhibitor under clinical development by Tolero ... Protein kinase inhibitors, Orphan drugs, All stub articles, Antineoplastic and immunomodulating drug stubs). ... 275 (37): 28345-8. doi:10.1074/jbc.C000446200. PMID 10906320. Chao SH, Price DH (2001). "Flavopiridol inactivates P-TEFb and ...
This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent ... kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs ... Serine/threonine-protein kinase PRP4 homolog is an enzyme that in humans is encoded by the PRPF4B gene. Pre-mRNA splicing ... 2002). "Mammalian PRP4 Kinase Copurifies and Interacts with Components of Both the U5 snRNP and the N-CoR Deacetylase Complexes ...
Cyclin D, Cyclin E transcriptional regulators: Myc, E2f1, p130 cyclin-dependent kinase inhibitors (CKIs): p27Kip1, p21, Wee1 ... βTRCP recognizes these substrates after they are phosphorylated by Polo-like kinase 1 or Cyclin B-CDK1. Fbw7, which is the ... Schwob, E (1994-10-21). "The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae". Cell. 79 ... SCF-fbxo4 plays a role in cell cycle control by targeting cyclin D1 for degradation. Cyclin F is an FBP that is associated with ...
Accumulation of cyclin B increases the activity of the cyclin dependent kinase Cdk1 human homolog Cdc2 as cells prepare to ... The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at ... Chk1 is an effector protein kinase that maintains mitotic cyclin in an inactive state and is phosphorylated by rad3 between S ... pathways which activate the Chk2 and Chk1 kinases, respectively. These kinases act upstream of Cdc25 and Wee1, the direct ...
Tyrosine kinases are enzymes that add phosphates to tyrosine residues, and are the opposing enzymes to PTPs. PTPs are known to ... cyclin D1 and c-myc. Expression of ful-length PTPkappa in melanoma cells that normally lack its expression results in reduced ... soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent ... "Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases". Genome Biol. 7 (1): R5. doi: ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase ... "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 ... A dose-dependent response was not observed, raising questions about the robustness of the findings. Genes,+tat at the US ... of cellular CDK9 and cyclin T1, and hence increases the production of full-length viral RNA. Tat protein also associates with ...
Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc. Natl. Acad. Sci. USA 2012, ... The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the ... PLoS One 2013, 8, e56707. [Google Scholar] [CrossRef][Green Version]. *Paik, S.; Tang, G.; Shak, S.; Kim, C.; Baker, J.; Kim, W ... BMC Cancer 2008, 8, 339. [Google Scholar] [CrossRef]. *Chia, S.K.; Bramwell, V.H.; Tu, D.; Shepherd, L.E.; Jiang, S.; Vickery, ...
Cyclin-Dependent Kinases [D08.811.913.696.620.682.700.646.500]. *Cyclin-Dependent Kinase 2 [D08.811.913.696.620.682.700.646. ... Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21. ... "Cyclin-Dependent Kinase 2" by people in Harvard Catalyst Profiles by year, and whether "Cyclin-Dependent Kinase 2" was a major ... Cyclin-Dependent Kinase 2 [D08.811.913.696.620.682.700.200.323]. *Proline-Directed Protein Kinases [D08.811.913.696.620.682. ...
The encoded protein interacts with cyclin-dependent kinase 8 and induces the phophorylation of the carboxy-terminal domain of ... The protein encoded by this gene is a member of the cyclin family of proteins. ...
Cyclin C D12.644.360.24.304.249 D12.644.360.24.309.249 D12.776.157.57.62.249 D12.776.157.57.72.249 Cyclin-Dependent Kinase 8 ... Receptor Protein-Tyrosine Kinases D12.776.543.750.60 D12.776.543.750.630 Receptor Tyrosine Kinase-like Orphan Receptors D12.776 ... Voltage-Dependent Anion Channel 1 D12.776.543.550.425.730.520.500 D12.776.543.550.450.730.520.500 Voltage-Dependent Anion ... Antibody-Dependent Cell Cytotoxicity G12.425.270.70 G12.287.70 Antibody-Dependent Enhancement G6.590.875.40 G6.920.95 G6.920. ...
... cycle arrest in human breast cancer cells is caused by p15 Ink4B and p27 Kip1-dependent inhibition of cyclin-dependent kinases ... Acute, dose-dependent cognitive effects of Ginkgo biloba, Panax ginseng and their combination in healthy young volunteers: ... Differential, dose dependent changes in cognitive performance following acute administration of a Ginkgo biloba/Panax ginseng ... Bai CX, Takahashi K, Masumiya H, Sawanobori T, Furukawa T. Nitric oxide-dependent modulation of the delayed rectifier K+ ...
9.Shapiro,G.I., Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006. 24(11):1770-83. 10.Platt ... and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. Mol Cell Biol. 1999. 19(3):1981-9. 75. ... Treatment of aHSCs with quercetin and gallic acid inhibited cell viability in a dose- and time-dependent manner. Results ... Additionally, quercetin limited aHSC proliferation by inducing a G1 arrest as evidenced by decreased expression of cyclin D1、D2 ...
Cyclin-dependent kinase 8 (CDK8) belongs to the transcription-related CDK family. Although CDK8 has been shown to be implicated ... Cyclin-dependent kinase 8 (CDK8) belongs to the transcription-related CDK family. Here, CDK8 in MSCs was identified as ... Extracellular signal-regulated kinase 5 (Erk5) belongs to the mitogen-activated protein kinase (MAPK) family. Previously, we ... We observed LAT1-dependent amino acid uptake in the hypothalamus, which was compromised in a mouse model of obesity and ...
Cdk8 Cyclin Dependent Kinase Cdk8 Cyclin-Dependent Kinase Cdk8 Protein Kinase Cell Division Protein Kinase 8 Cyclin Dependent ... Cyclin-Dependent Kinase, Cdk8 Kinase, Cdk8 Cyclin-Dependent Kinase, Cdk8 Protein Protein Kinase, Cdk8 ... Cdk8 Cyclin Dependent Kinase. Cdk8 Cyclin-Dependent Kinase. Cdk8 Protein Kinase. Cell Division Protein Kinase 8. Cyclin ... Cyclin-Dependent Kinase, Cdk8. Kinase, Cdk8 Cyclin-Dependent. Kinase, Cdk8 Protein. Protein Kinase, Cdk8. ...
Protein Kinase Activity. *Cyclin-dependent Protein Serine/threonine Kinase Activity. *Protein Binding ... TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain ...
Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma. Pathology, research and practice 2022 Jul ...
Loss of Cyclin-dependent Kinase 2 in the Pancreas Links Primary β-Cell Dysfunction to Progressive Depletion of β-Cell Mass and ... Cyclin-dependent kinase 4 expression is essential for neu-induced breast tumorigenesis.. Reddy HK, Mettus RV, Rane SG, Graña X ... 8:30 a.m.. to 5 p.m.. ET, Monday - Friday Email: [email protected] Phone: +1-800-860-8747 TTY: +711 Chat. Live Chat ... Janus kinases: components of multiple signaling pathways.. Rane SG, Reddy EP.. Oncogene (2000 Nov 20) 19:5662-79. Abstract/Full ...
Cyclin C D12.644.360.24.304.249 D12.644.360.24.309.249 D12.776.157.57.62.249 D12.776.157.57.72.249 Cyclin-Dependent Kinase 8 ... Receptor Protein-Tyrosine Kinases D12.776.543.750.60 D12.776.543.750.630 Receptor Tyrosine Kinase-like Orphan Receptors D12.776 ... Voltage-Dependent Anion Channel 1 D12.776.543.550.425.730.520.500 D12.776.543.550.450.730.520.500 Voltage-Dependent Anion ... Antibody-Dependent Cell Cytotoxicity G12.425.270.70 G12.287.70 Antibody-Dependent Enhancement G6.590.875.40 G6.920.95 G6.920. ...
When directed to the nucleus by TGF-β or BMP signals, Smad proteins undergo cyclin-dependent kinase 8/9 (CDK8/9) and glycogen ... Of the G(1) cell cycle factors examined, the expression of cyclin-dependent kinase 6 (Cdk6) was found to be strongly down- ... The stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) is also one of the downstream targets required for ... Bmp2-dependent stimulation of Myc transcription is dependent on contributions by each of Tcf4, ß-catenin and Smad1. These ...
... the LTag inactivation of p53 allows the re-phosphorylation of pRb through the cyclin-dependent kinase (cdk) pathway and ... the cDNA coding sequence of LTag of BKV is under control of a tetracycline-controlled transactivator-dependent promoter. The ... 8]. Within these modalities of virus-cell interaction, LTag is the most highly expressed BKV antigen in non permissive infected ... prevents the p53-mediated cell apoptosis of infected cell[8].. This mechanism is used by the virus to keep the infected cells ...
Each system includes kinase and substrate pairs in an easy-to-use 8-tube strip format optimized for fast and simple kinase ... Easy-to-use kits for performing kinase selectivity profiling that rely on the ADP-Glo Kinase Assay technology. ... The CMGC-1 and CMGC-2 Kinase Selectivity Profiling Systems contain cyclin-dependent kinases (CDKs), mitogen-activated protein ... Kinase Selectivity Profiling Systems-CAMK1 and CAMK2. Calcium/calmodulin-dependent kinases and substrates in an 8-tube strip ...
2013) Inhibition of NF-κB-mediated signaling by the cyclin-dependent kinase inhibitor CR8 overcomes pro-survival stimuli to ... 2013) Inhibition of NF-κB-mediated signaling by the cyclin-dependent kinase inhibitor CR8 overcomes pro-survival stimuli to ... Investigating the potential of novel cyclin dependent kinase inhibitors as a novel therapeutic agents in the treatment of ... Michie, A. M. , McCaig, A. M., Nakagawa, R. and Vukovic, M. (2010) Death-associated protein kinase (DAPK) and signal ...
Cyclin-Dependent Kinase 8. Quinasa 8 Dependiente de la Ciclina. Receptor Nuclear Órfão DAX-1. DAX-1 Orphan Nuclear Receptor. ... Cyclin-Dependent Kinase 8. Quinasa 8 Dependiente de la Ciclina. Subunidade 1 do Complexo Mediador. Mediator Complex Subunit 1. ... Cyclin-Dependent Kinase 3. Quinasa 3 Dependiente de la Ciclina. Quinase 8 Dependente de Ciclina. Cyclin-Dependent Kinase 8. ... Cyclin-Dependent Kinase 3. Quinasa 3 Dependiente de la Ciclina. Quinase 8 Dependente de Ciclina. ...
Cyclin-Dependent Kinase 8. Quinasa 8 Dependiente de la Ciclina. Receptor Nuclear Órfão DAX-1. DAX-1 Orphan Nuclear Receptor. ... Cyclin-Dependent Kinase 8. Quinasa 8 Dependiente de la Ciclina. Subunidade 1 do Complexo Mediador. Mediator Complex Subunit 1. ... Cyclin-Dependent Kinase 3. Quinasa 3 Dependiente de la Ciclina. Quinase 8 Dependente de Ciclina. Cyclin-Dependent Kinase 8. ... Cyclin-Dependent Kinase 3. Quinasa 3 Dependiente de la Ciclina. Quinase 8 Dependente de Ciclina. ...
Cyclin-Dependent Kinase 8. Quinasa 8 Dependiente de la Ciclina. Receptor Nuclear Órfão DAX-1. DAX-1 Orphan Nuclear Receptor. ... Cyclin-Dependent Kinase 8. Quinasa 8 Dependiente de la Ciclina. Subunidade 1 do Complexo Mediador. Mediator Complex Subunit 1. ... Cyclin-Dependent Kinase 3. Quinasa 3 Dependiente de la Ciclina. Quinase 8 Dependente de Ciclina. Cyclin-Dependent Kinase 8. ... Cyclin-Dependent Kinase 3. Quinasa 3 Dependiente de la Ciclina. Quinase 8 Dependente de Ciclina. ...
MAZ increases cyclin-dependent kinase inhibitor 1A (CDKN1A) expression [38] and is known to regulate MYC transcription [45] - ... and the cyclin-dependent kinase inhibitor, CDKN1A, appeared as hubs within this subnetwork, suggesting a novel connection ... of serum amyloid A-activating factor 1 inhibits cell proliferation by the induction of cyclin-dependent protein kinase ... MAZ is also activated by both IL1 and IL6 through MAP kinase-dependent phosphorylation in human cells [39] and is a member of ...
Human CDK6(Cyclin Dependent Kinase 6) ELISA Kit. *Human CDK8(Cyclin Dependent Kinase 8) ELISA Kit ... Human PPM1A(Protein Phosphatase, Mg2+/Mn2+ Dependent 1A) ELISA Kit. *Human PPP1R1B(Protein Phosphatase 1, Regulatory Subunit 1B ... Human DYRK1A(Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A) ELISA Kit. *Human E2F1(E2F Transcription Factor 1) ... Human IkBKb(Inhibitor Of Kappa-Light Polypeptide Gene Enhancer In B-Cells Kinase Beta) ELISA Kit ...
Mouse CDK8(Cyclin Dependent Kinase 8) ELISA Kit. *Mouse RXRa(Retinoid X Receptor Alpha) ELISA Kit ... Mouse PRKDC(Protein Kinase, DNA Activated, Catalytic Polypeptide) ELISA Kit. *Mouse DAPK1(Death Associated Protein Kinase 1) ... Rat GSK3b(Glycogen Synthase Kinase 3 Beta) ELISA Kit. *Human TOMM70A(Translocase Of Outer Mitochondrial Membrane 70A) ELISA Kit ... Human RPS6Kb1(Ribosomal Protein S6 Kinase Beta 1) ELISA Kit. *Cattle TIMP1(Tissue Inhibitors Of Metalloproteinase 1) ELISA Kit ...
Mouse CDK8(Cyclin Dependent Kinase 8) ELISA Kit. *Mouse CHRDL2(Chordin Like Protein 2) ELISA Kit ... Human CAMKK2(Calcium/Calmodulin Dependent Protein Kinase Kinase 2) ELISA Kit. *Human CCT2(Chaperonin Containing TCP1, Subunit 2 ... Rat MAPK14(Mitogen Activated Protein Kinase 14) ELISA Kit. *Rat MARCKS(Myristoylated Alanine Rich Protein Kinase C Substrate) ... Rat RIPK1(Receptor Interacting Serine Threonine Kinase 1) ELISA Kit. *Rat RIPK3(Receptor Interacting Serine Threonine Kinase 3 ...
Human CDK6(Cyclin Dependent Kinase 6) ELISA Kit. *Human CDK8(Cyclin Dependent Kinase 8) ELISA Kit ... Human PPM1A(Protein Phosphatase, Mg2+/Mn2+ Dependent 1A) ELISA Kit. *Human PPP1R1B(Protein Phosphatase 1, Regulatory Subunit 1B ... Human PPM1A(Protein Phosphatase, Mg2+/Mn2+ Dependent 1A) ELISA Kit. *Human PPP1R1B(Protein Phosphatase 1, Regulatory Subunit 1B ... Human DYRK1A(Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A) ELISA Kit. *Human E2F1(E2F Transcription Factor 1) ...
Human CDK6(Cyclin Dependent Kinase 6) ELISA Kit. *Human CDK8(Cyclin Dependent Kinase 8) ELISA Kit ... Human PPM1A(Protein Phosphatase, Mg2+/Mn2+ Dependent 1A) ELISA Kit. *Human PPP1R1B(Protein Phosphatase 1, Regulatory Subunit 1B ... Human PPM1A(Protein Phosphatase, Mg2+/Mn2+ Dependent 1A) ELISA Kit. *Human PPP1R1B(Protein Phosphatase 1, Regulatory Subunit 1B ... Human DYRK1A(Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A) ELISA Kit. *Human E2F1(E2F Transcription Factor 1) ...
7. Takatsuka H, Umeda-Hara C, Umeda M (2015) Cyclin-dependent kinase-activating kinases CDKD;1 and CDKD;3 are essential for ... 2008) Targeted degradation of the cyclin-dependent kinase inhibitor ICK4/KRP6 by RING-type E3 ligases is essential for mitotic ... 2012) Genetic framework of cyclin-dependent kinase function in Arabidopsis. Dev Cell 22: 1030-1040. doi: 10.1016/j.devcel. ... Článek Aurora kinase A is essential for meiosis in mouse oocytes Článek Pathways and signatures of mutagenesis at targeted DNA ...
... glycogen synthase kinase 3 (GSK-3), cyclin-dependent kinase 5 (CDK5) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) ... Serine/threonine kinases are protein kinases that take part in the regulation of cellular functions. At least protein kinase C ... The success of the neurotrophic factor treatment is dependent on a successful injection of protein or viral vector, and the ... PKC is an interesting kinase considering this project. It has been shown that PKC activation prevents the formation of amyloid ...
Cyclin-Dependent Kinases [D08.811.913.696.620.682.700.646.500]. *Cyclin-Dependent Kinase 3 [D08.811.913.696.620.682.700.646. ... "Cyclin-Dependent Kinase 3" by people in this website by year, and whether "Cyclin-Dependent Kinase 3" was a major or minor ... 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 ... "Cyclin-Dependent Kinase 3" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ...
  • In the course of our investigations to discover new CDK8 inhibitors, we designed and synthesized tricyclic pyrido[2,3-b][1,5]benzoxazepin-5(6H)-one derivatives, by introduction of chemical complexity in the multi-kinase inhibitor Sorafenib taking into account the flexibility of the P-loop motif of CDK8 protein observed after analysis of structural information of co-crystallized CDK8 inhibitors. (nih.gov)
  • 17. CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases. (nih.gov)
  • 2007) The cyclin-dependent kinase inhibitor Dacapo promotes replication licensing during Drosophila endocycles. (nih.gov)
  • 107 received EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy (T), 53 received EGFR-TKI + bevacizumab (T + A), and 36 received EGFR-TKI + bevacizumab + chemotherapy (T + A + C). The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events (AEs). (bvsalud.org)
  • Cyclin dependent kinase inhibitor proteins. (lookformedical.com)
  • It is an endogenous inhibitor of RAF KINASES and may play a role in regulating SIGNAL TRANSDUCTION. (lookformedical.com)
  • A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. (lookformedical.com)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (lookformedical.com)
  • Because a variety of cyclin-dependent kinases (CDKs) assist the effects of EZH2 and cyclin D1, the researchers wanted to see if targeting CDKs in ATRTs with the multi-CDK inhibitor TG02 could have therapeutic effects. (physiciansweekly.com)
  • E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. (nih.gov)
  • 10. Enzyme-linked immunosorbent assay for distinct cyclin-dependent kinase activities using phosphorylation-site-specific anti-pRB monoclonal antibodies. (nih.gov)
  • Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception. (nih.gov)
  • Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. (lookformedical.com)
  • Cyclin-dependent kinases (Cdks) coordinate hundreds of molecular events during the cell cycle via Ser/Thr phosphorylation. (eu.org)
  • Docking motifs control the timing of cell cycle events by enabling preferential interaction and phosphorylation of substrates by a specific cyclin/Cdk complex. (eu.org)
  • Inhibition of DNA binding by the phosphorylation of poly ADP-ribose polymerase protein catalysed by protein kinase C. Biochem Biophys Res Commun 187 , 730-736. (nih.gov)
  • Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. (nih.gov)
  • 14. Small molecules as inhibitors of cyclin-dependent kinases. (nih.gov)
  • 3. Biaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. (nih.gov)
  • 5. Heterobiaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. (nih.gov)
  • 8. Roscovitine-derived, dual-specificity inhibitors of cyclin-dependent kinases and casein kinases 1. (nih.gov)
  • 11. Synthesis and biological evaluation of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of cyclin-dependent kinases. (nih.gov)
  • 12. 8-Azapurines as new inhibitors of cyclin-dependent kinases. (nih.gov)
  • 4. Cyclin-dependent kinase and protein kinase C inhibitors: a novel class of antineoplastic agents in clinical development. (nih.gov)
  • It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. (harvard.edu)
  • The protein encoded by this gene is a member of the cyclin family of proteins. (prosci-inc.com)
  • The encoded protein interacts with cyclin-dependent kinase 8 and induces the phophorylation of the carboxy-terminal domain of the large subunit of RNA polymerase II. (prosci-inc.com)
  • This gene encodes a member of the cyclin-dependent protein kinase (CDK) family. (nih.gov)
  • The STB identified the CDK8 amplification and Ras mutation as providing a rationale for clinical trials with CDK inhibitors or MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase) and PI3K (phosphatidylinositol 3-kinase) inhibitors, respectively. (nih.gov)
  • Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (lookformedical.com)
  • 8 Active and inactive Cyclin-dependent protein kinase structures. (pipoforex.com)
  • Interaction between replication protein A and p53 is disrupted after UV damage in a DNA repair-dependent manner. (nih.gov)
  • Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation. (nih.gov)
  • Single-stranded-DNA binding alters human replication protein A structure and facilitates interaction with DNA-dependent protein kinase. (nih.gov)
  • 15. A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors. (nih.gov)
  • Growth arrest was attributed to inhibition of G1-phase cyclin-dependent kinase 2 (CDK2) activity. (nih.gov)
  • Human myt1 is a cell cycle-regulated kinase that inhibits cdc2 but not cdk2 activity. (nih.gov)
  • In the present study, we show that BRMS1 is a novel substrate of Cyclin-Dependent Kinase 2 (CDK2) that is phosphorylated on serine 237 (S237). (edu.au)
  • CDK2 limits the highly energetic secretory program of mature β cells by restricting PEP cycle-dependent K(ATP) channel closure. (nih.gov)
  • CDK8 is a cyclin-dependent kinase that forms part of the mediator complex, and modulates the transcriptional output from distinct transcription factors involved in oncogenic control. (nih.gov)
  • The first patient had metastatic colorectal cancer in which we identified somatic point mutations in NRAS, TP53, AURKA, FAS, and MYH11, plus amplification and overexpression of cyclin-dependent kinase 8 (CDK8). (nih.gov)
  • Robin Weinmann has worked on the regulation of cyclin-dependent kinase 8 and 19 (CDK8 / CDK19) activity in the mediator complex at the University of Bayreuth where he obtained his Master's degree. (uni-heidelberg.de)
  • A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. (lookformedical.com)
  • 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. (lookformedical.com)
  • A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. (lookformedical.com)
  • Cyclins use the conserved hydrophobic pocket (hp) to bind docking motifs on partner proteins. (eu.org)
  • Rotelli M, Policastro R, Bolling A, Killion A, Weinberg A, Dixon M, Zentner G, Walczak C, Lilly MA, Calvi B. (2019) A Cyclin A-Myb-Aurora B network regulates the choice between mitotic cycles and polyploid endoreplication cycles. (nih.gov)
  • Jan 3;8(1):1, 2019. (nih.gov)
  • Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. (umassmed.edu)
  • 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. (lookformedical.com)
  • 2006) Bruno inhibits the expression of mitotic cyclins during the prophase I meiotic arrest of Drosophila oocytes. (nih.gov)
  • Previous studies in hepatocyte-derived cell lines and the whole liver established that the aryl hydrocarbon receptor (AhR) can disrupt G1-phase cell cycle progression following exposure to persistent AhR agonists, such as TCDD (dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin). (nih.gov)
  • With cell cycle progression, different cyclins bind to Cdks to control their function by providing docking sites for substrates and also by modulating Cdk active site specificity. (eu.org)
  • The sequential attachment of different cyclins to Cdks represents the periodic driving force that ensures a controlled progression through the cell cycle. (eu.org)
  • Cyclins Cln1-3 are triggers for G1 and G1/S, while among B-type cyclins Clb5 and Clb6 drive S phase, Clb3 and Clb4 are specific for early mitotic events, and Clb1 and Clb2 complete the progression to mitosis. (eu.org)
  • 16. 3-Acyl-2,6-diaminopyridines as cyclin-dependent kinase inhibitors: synthesis and biological evaluation. (nih.gov)
  • 1. Synthesis and biological evaluation of selective and potent cyclin-dependent kinase inhibitors. (nih.gov)
  • 2. Synthesis and in vitro biological evaluation of 2,6,9-trisubstituted purines targeting multiple cyclin-dependent kinases. (nih.gov)
  • 6. Synthesis and biological evaluation of N9-cis-cyclobutylpurine derivatives for use as cyclin-dependent kinase (CDK) inhibitors. (nih.gov)
  • 10. Synthesis and biological activities of 4-substituted pyrrolo[2,3-a]carbazole Pim kinase inhibitors. (nih.gov)
  • Synthesis and Structure-Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold. (harvard.edu)
  • The enzyme is activated by its interaction with CYCLIN C and plays a role in transcriptional regulation by phosphorylating RNA POLYMERASE II. (ouhsc.edu)
  • Limited evidence suggests that these mechanisms have parallels in mammalian cyclin-Cdk regulation. (eu.org)
  • 2. ATP-noncompetitive inhibitors of CDK-cyclin complexes. (nih.gov)
  • Although there can be functional overlap, the various cyclin/Cdk complexes are specialized for optimum performance of discrete tasks. (eu.org)
  • Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms. (lookformedical.com)
  • Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1. (harvard.edu)
  • Cyclin-dependent kinases regulate the antiproliferative function of Smads. (nih.gov)
  • A CYCLIN C dependent kinase that is an important component of the mediator complex. (ouhsc.edu)
  • Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. (nih.gov)
  • The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2. (lookformedical.com)
  • Assessment of the regenerative process in wild-type, p21(Cip1) knockout, and p27(Kip1) knockout mice confirmed that TCDD-induced inhibition of liver regeneration is entirely dependent on p21(Cip1) expression. (nih.gov)
  • Analysis of the transcriptional response determined that increased p21(Cip1) expression during liver regeneration involved an AhR-dependent mechanism. (nih.gov)
  • Cyclin-Dependent Kinase 8" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (ouhsc.edu)
  • Sci Rep. Jan 19;8(1):1177, 2018. (nih.gov)
  • 19. Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine. (nih.gov)
  • Cyclin-dependent kinases (Cdks) are central regulatory enzymes of the eukaryotic cell cycle. (eu.org)
  • Previously, cyclin D1 and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase linked in numerous malignancies, were identified as major drivers of tumorigenicity in ATRTs in genetic studies. (physiciansweekly.com)
  • Additionally, quercetin limited aHSC proliferation by inducing a G1 arrest as evidenced by decreased expression of cyclin D1、D2、A、B1、E. Moreover quercetin and gallic acid induced aHSC apoptosis via Fas/Fas ligand-mediated extrinsic pathway. (ncl.edu.tw)
  • Cyclins may use additional surfaces to dock substrates, as with the mammalian Cyclin D-specific ( DOC_CYCLIN_D_Helix_1 ) and the budding yeast Cln2-specific leucine- and proline-rich LP ( DOC_CYCLIN_yCln2_LP_2 ) motifs. (eu.org)
  • The requirement for cyclin E in c-Myc overexpressing breast cancers. (harvard.edu)
  • Here a single Cdk, Cdk1, associates with different cyclins to mediate all major cell cycle transitions. (eu.org)
  • FKBP39 controls nutrient dependent Nprl3 expression and TORC1 activity in Drosophila. (nih.gov)
  • NSun2 Promotes Cell Growth via Elevating Cyclin-Dependent Kinase 1 Translation. (oajrc.org)
  • 15. [Chemical inhibitors of cyclic-dependent kinases: preclinical and clinical study]. (nih.gov)
  • 1. Recent advances and new directions in the discovery and development of cyclin-dependent kinase inhibitors. (nih.gov)
  • It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. (lookformedical.com)
  • 17. Coming full circle: cyclin-dependent kinases as anti-cancer drug targets. (nih.gov)
  • A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. (lookformedical.com)

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