Cyclin-Dependent Kinases
Cyclin-Dependent Kinase 2
Cyclin D1
Cyclin A
Cyclin E
Cyclins
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p27
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
CDC2-CDC28 Kinases
Cell Cycle
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase 5
Cell Cycle Proteins
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
Cyclin B
Cyclin C
Protein-Serine-Threonine Kinases
CDC2 Protein Kinase
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Cyclin D
G1 Phase
Cyclin-Dependent Kinase Inhibitor p16
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.
Cyclin-Dependent Kinase Inhibitor Proteins
Cyclin D3
Cyclin B1
Retinoblastoma Protein
Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.
Phosphorylation
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase Inhibitor p57
Tumor Suppressor Proteins
S Phase
Cyclin D2
Cyclin A1
Microtubule-Associated Proteins
Protein Kinases
Purines
Cell Division
Apoptosis
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Proto-Oncogene Proteins
E2F1 Transcription Factor
Cyclin A2
Phosphatidylinositol 3-Kinases
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.
Cyclin G
Tumor Cells, Cultured
Tumor Suppressor Protein p53
Mitosis
Cyclin G1
MAP Kinase Signaling System
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.
Transcription Factor DP1
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cells, Cultured
Blotting, Western
Enzyme Inhibitors
G2 Phase
E2F Transcription Factors
A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.
Transfection
Calcium-Calmodulin-Dependent Protein Kinases
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)
Mutation
Proliferating Cell Nuclear Antigen
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Molecular Sequence Data
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.
DNA-Binding Proteins
Carrier Proteins
Nuclear Proteins
Base Sequence
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Protein Kinase C
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.
Transcription Factors
src-Family Kinases
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.
Immunohistochemistry
Reverse Transcriptase Polymerase Chain Reaction
DNA Damage
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
Amino Acid Sequence
p38 Mitogen-Activated Protein Kinases
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.
Cyclic AMP-Dependent Protein Kinases
Cyclin B2
Mitogen-Activated Protein Kinase 1
Protein Binding
Enzyme Activation
Gene Expression Regulation
Transcription, Genetic
Cyclin T
Mitogen-Activated Protein Kinase Kinases
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.
p21-Activated Kinases
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Cyclin H
Cyclin G2
Calcium-Calmodulin-Dependent Protein Kinase Type 2
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.
MAP Kinase Kinase Kinases
Recombinant Fusion Proteins
3T3 Cells
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Creatine Kinase
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.
Models, Biological
Calcium
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.
Casein Kinase II
eIF-2 Kinase
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.
Intracellular Signaling Peptides and Proteins
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.
Binding Sites
Cell Nucleus
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Ribosomal Protein S6 Kinases
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.
Mitogen-Activated Protein 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).
MAP Kinase Kinase 1
Down-Regulation
Extracellular Signal-Regulated MAP Kinases
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.
Casein Kinases
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.
Serine
Pyruvate Kinase
Glycogen Synthase Kinase 3
RNA, Small Interfering
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Promoter Regions, Genetic
Receptor Protein-Tyrosine Kinases
Mice, Knockout
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.
Thymidine Kinase
MAP Kinase Kinase 4
Saccharomyces cerevisiae Proteins
Isoenzymes
Phosphotransferases (Alcohol Group Acceptor)
I-kappa B Kinase
Proto-Oncogene Proteins c-akt
E2F4 Transcription Factor
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
DNA Primers
1-Phosphatidylinositol 4-Kinase
Aurora Kinases
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.
rho-Associated Kinases
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.
Protein Kinase C-alpha
HeLa Cells
S Phase Cell Cycle Checkpoints
Protein Kinase C-delta
Saccharomyces cerevisiae
Rats, Sprague-Dawley
Substrate Specificity
Gene Expression Regulation, Neoplastic
Proteins
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Oncogene Proteins
Transcriptional Activation
AMP-Activated Protein Kinases
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.
Immunoblotting
Cyclin I
Flow Cytometry
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Tyrosine
Dose-Response Relationship, Drug
Sequence Homology, Amino Acid
Diacylglycerol Kinase
Precipitin Tests
Retinoblastoma-Binding Protein 1
Focal Adhesion Kinase 1
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.
Neoplasm Proteins
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Fibroblasts
Janus Kinase 2
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.
Tetradecanoylphorbol Acetate
Myosin-Light-Chain Kinase
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.
Focal Adhesion Protein-Tyrosine Kinases
Ribosomal Protein S6 Kinases, 90-kDa
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.
TOR Serine-Threonine Kinases
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.
Neurons
Threonine
Gene Expression
Cloning, Molecular
Protein Kinase C-epsilon
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.
Cyclic AMP
MAP Kinase Kinase 2
Androstadienes
MAP Kinase Kinase Kinase 1
Cell Survival
Up-Regulation
Genes, bcl-1
Protein Kinase C beta
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.
Gene Expression Regulation, Enzymologic
Cell Differentiation
Cyclic GMP-Dependent Protein Kinases
RNA Interference
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.
Protein Transport
Membrane Proteins
DNA
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Adenosine Triphosphate
Adaptor Proteins, Signal Transducing
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
Phosphoprotein Phosphatases
Trans-Activators
Cell Membrane
Genes, p16
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.
Mitogen-Activated Protein Kinase 8
Mutagenesis, Site-Directed
Phosphoglycerate Kinase
Casein Kinase I
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.
NF-kappa B
MAP Kinase Kinase 6
Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (1/363)
The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules. (+info)Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (2/363)
The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +info)Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (3/363)
The response of the uterine epithelium to female sex steroid hormones provides an excellent model to study cell proliferation in vivo since both stimulation and inhibition of cell proliferation can be studied. Thus, when administered to ovariectomized adult mice 17beta-estradiol (E2) stimulates a synchronized wave of DNA synthesis and cell division in the epithelial cells, while pretreatment with progesterone (P4) completely inhibits this E2-induced cell proliferation. Using a simple method to isolate the uterine epithelium with high purity, we have shown that E2 treatment induces a relocalization of cyclin D1 and, to a lesser extent, cdk4 from the cytoplasm into the nucleus and results in the orderly activation of cyclin E- and cyclin A-cdk2 kinases and hyperphosphorylation of pRb and p107. P4 pretreatment did not alter overall levels of cyclin D1, cdk4, or cdk6 nor their associated kinase activities but instead inhibited the E2-induced nuclear localization of cyclin D1 to below the control level and, to a lesser extent, nuclear cdk4 levels, with a consequent inhibition of pRb and p107 phosphorylation. In addition, it abrogated E2-induced cyclin E-cdk2 activation by dephosphorylation of cdk2, followed by inhibition of cyclin A expression and consequently of cyclin A-cdk2 kinase activity and further inhibition of phosphorylation of pRb and p107. P4 is used therapeutically to oppose the effect of E2 during hormone replacement therapy and in the treatment of uterine adenocarcinoma. This study showing a novel mechanism of cell cycle inhibition by P4 may provide the basis for the development of new antiestrogens. (+info)Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state. (4/363)
We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16ink4a in response to treatment with a demethylating agent. (+info)NF-kappaB function in growth control: regulation of cyclin D1 expression and G0/G1-to-S-phase transition. (5/363)
Nuclear factor kappa B (NF-kappaB) has been implicated in the regulation of cell proliferation, transformation, and tumor development. We provide evidence for a direct link between NF-kappaB activity and cell cycle regulation. NF-kappaB was found to stimulate transcription of cyclin D1, a key regulator of G1 checkpoint control. Two NF-kappaB binding sites in the human cyclin D1 promoter conferred activation by NF-kappaB as well as by growth factors. Both levels and kinetics of cyclin D1 expression during G1 phase were controlled by NF-kappaB. Moreover, inhibition of NF-kappaB caused a pronounced reduction of serum-induced cyclin D1-associated kinase activity and resulted in delayed phosphorylation of the retinoblastoma protein. Furthermore, NF-kappaB promotes G1-to-S-phase transition in mouse embryonal fibroblasts and in T47D mammary carcinoma cells. Impaired cell cycle progression of T47D cells expressing an NF-kappaB superrepressor (IkappaBalphaDeltaN) could be rescued by ectopic expression of cyclin D1. Thus, NF-kappaB contributes to cell cycle progression, and one of its targets might be cyclin D1. (+info)Activation of cyclin A gene expression by the cyclin encoded by human herpesvirus-8. (6/363)
Human herpesvirus-8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, encodes a protein, referred to as HHV8-Vcyc, with sequence similarity to human G1 cyclins, in particular of the D type. HHV8-Vcyc is expressed in Kaposi's sarcoma and functional analysis suggests that it can activate cyclin-dependent kinases (cdk) and thereby trigger inactivation of the retinoblastoma protein (pRb), indicating that HHV8-Vcyc may contribute to the oncogenic potential of HHV-8. We show here that HHV8-Vcyc can activate transcription of the human cyclin A gene in quiescent cells, a property shared with known transforming oncogenes. Transcriptional activation by HHV8-Vcyc depends on an E2F-binding site in the cyclin A promoter, and cdk6 kinase activity is required. The ability of HHV8-Vcyc to activate cyclin A gene expression is shared by D-type cyclins and cyclin E. Unlike D-type cyclins, HHV8-Vcyc is unable to trigger phosphorylation of the pRb-related protein p107 and fails to induce dissociation of p107 from E2F. Unlike cyclin E, HHV8-Vcyc fails to interact physically with E2F complexes on the cyclin A promoter. These results provide additional evidence for the notion that the HHV-8-encoded cyclin differs in several properties from cellular G1 cyclins. (+info)Anchorage dependence of mitogen-induced G1 to S transition in primary T lymphocytes. (7/363)
Anchorage dependence defines the cellular requirement for integrin-mediated adhesion to substrate to initiate DNA replication in response to growth factors. In this study we investigated whether normal T cells, which spend extended periods in a nonadherent state, show similar requirements for cell cycle progression in response to TCR stimulation. Resting primary T lymphocytes were induced to enter the cell cycle by TCR triggering, and leukocyte integrins were either engaged using purified ICAM-1 or inhibited with function-blocking mAbs. Our data indicate that leukocyte integrins complement TCR-driven mitogenic signals not as a result of their direct clustering but, rather, via integrin-dependent organization of the actin cytoskeleton. Leukocyte integrin-dependent reorganization of the actin cytoskeleton cooperates with the TCR to effect mitogen-activated protein kinase activation, but also represents a required late (4-8 h poststimulation) component in the mitogenic response of normal T cells. Prolonged leukocyte integrin-dependent spreading, in the context of intercellular contact, is a requisite for the production of the mitogenic cytokine IL-2, which, in turn, is involved in the induction of D3 cyclin and is primarily responsible for the decrease in the cyclin-dependent kinase inhibitor p27kip, resulting in retinoblastoma protein inactivation and S phase entry. Thus, T lymphocytes represent a peculiar case of anchorage dependence, in which signals conveyed by integrins act sequentially with the activating stimulus to effect a sustained production of the essential mitogenic cytokine. (+info)CTLA-4-Mediated inhibition of early events of T cell proliferation. (8/363)
CTLA-4 engagement by mAbs inhibits, while CD28 enhances, IL-2 production and proliferation upon T cell activation. Here, we have analyzed the mechanisms involved in CTLA-4-mediated inhibition of T cell activation of naive CD4+ T cells using Ab cross-linking. CTLA-4 ligation inhibited CD3/CD28-induced IL-2 mRNA accumulation by inhibiting IL-2 transcription, which appears to be mediated in part through decreasing NF-AT accumulation in the nuclei. However, CTLA-4 ligation did not appear to affect the CD28-mediated stabilization of IL-2 mRNA. Further, CTLA-4 engagement inhibited progression through the cell cycle by inhibiting the production of cyclin D3, cyclin-dependent kinase (cdk)4, and cdk6 when the T cells were stimulated with anti-CD3/CD28 and with anti-CD3 alone. These results indicate that CTLA-4 signaling inhibits events early in T cell activation both at IL-2 transcription and at the level of IL-2-independent events of the cell cycle, and does not simply oppose CD28-mediated costimulation. (+info)
RCSB PDB - 1JOW: Crystal structure of a complex of human CDK6 and a viral cyclin
P 276 - AdisInsight
Alsterpaullone (CAS 237430-03-4) 96% purity (ab141070) |Abcam
Trial in progress: A phase 3, randomized, double-blind trial of trilaciclib versus placebo in patients receiving first- or...
Gentaur Molecular :GenWay \ Cyclin-Dependent Kinase 4 - EC 2.7.11.22; Cyclin-dependent kinase 4; PSK-J3 \ 10-288-22309F
Cyclin-Dependent Kinase 2 | Colorado PROFILES
Cyclin-Dependent Kinase 10 (CDK10) (AA 1-361) protein (His tag)</span...
Cyclin-Dependent Kinase 10 (CDK10) (AA 1-360) protein (His tag)</span...
Cdk11b MGI Mouse Gene Detail - MGI:88353 - cyclin-dependent kinase 11B
CDK5ELISA试剂盒产品概述
CDK5R1ELISA试剂盒产品概述
Phosphorylation of Sic1, a Cyclin-dependent Kinase (Cdk) Inhib...
An analysis of available biomarker data for targeting cyclin-dependent kinases 4 and 6 (CDK4/6) in breast cancer - Fingerprint
...
OriGene - Cdk14 (NM 011074) Human ORF cDNA Clone
RCSB PDB - Launch Viewer
for 1GIH
Sequence Detail
AZD5438 | ≥99%(HPLC) | Selleck | CDK inhibitor
Cyclin-dependent kinase 15 | definition of cyclin-dependent kinase 15 by Medical dictionary
Cdk5r1 - Cyclin-dependent kinase 5 activator - Mus musculus (Mouse) - Cdk5r1 gene & protein
WikiGenes - CDK1 - cyclin-dependent kinase 1
OriGene - Cdk5r1 (NM 053891) Human ORF cDNA Clone
FBXO27抗体|Abcam中国|Anti-FBXO27抗体
Coordinate Control of Proliferation and Migration by the p27Kip1/Cyclin-Dependent Kinase/Retinoblastoma Pathway in Vascular...
Cyclin-Dependent Kinase 6
Summary Report | CureHunter
Cyclin-Dependent Kinase 4
Summary Report | CureHunter
Mouse monoclonal antibody to Cyclin-dependent kinase 4 inhibitor D [IMD-19]: IgG
Large-scale RNAi screens identify novel genes that interact with the C. elegans retinoblastoma pathway as well as splicing...
Cyclin-dependent kinases | Genome Biology | Full Text
Loss of cyclin-dependent kinase 5 from parvalbumin interneurons leads to hyperinhibition, decreased anxiety, and memory...
Selective Inhibition of CDK4 and CDK6 Primes Chemoresistant Myeloma Cell for Cytotoxic Killing through Induction of Cell Cycle...
cialis dose recomendada
cattattoo #crazycatlady #catofinstagram #ink #inked #inkart #tattooart #tattoolife #tattoolove #tattoopassion ...
MicroRNA 495
"MicroRNA-495 inhibits proliferation of glioblastoma multiforme cells by downregulating cyclin-dependent kinase 6". World J Surg ...
Splenic marginal zone lymphoma
November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ... Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ... 40 (6): 642-51. doi:10.1136/jcp.40.6.642. PMC 1141055. PMID 3497180. Berger F, Felman P, Thieblemont C, et al. (March 2000). " ...
CDKN2C
... has been shown to interact with Cyclin-dependent kinase 4 and Cyclin-dependent kinase 6. GRCh38: Ensembl release 89: ... Cyclin-dependent kinase 4 inhibitor C is an enzyme that in humans is encoded by the CDKN2C gene. The protein encoded by this ... "Entrez Gene: CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)". Ewing RM, Chu P, Elisma F, Li H, Taylor P, ... Fåhraeus R, Laín S, Ball KL, Lane DP (1998). "Characterization of the cyclin-dependent kinase inhibitory domain of the INK4 ...
Mariano Barbacid
Malumbres M, Ortega S, Barbacid M. «Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors.» Biol Chem ... Toll-like Receptor-4 (TLR4) Down-regulates MicroRNA-107, Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6.» J Biol ... Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6." (2011) His scientific career has been awarded with prizes such ... "Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors." (2000). "Toll-like Receptor-4 (TLR4) Down- ...
Mir-129 microRNA precursor family
There is evidence to suggest that miR-129 directly targets Cdk6, cyclin dependant kinase 6- a cell proliferation regulator. ... 2004). "Cell cycle-dependent transcriptional regulation of calmodulin-binding transcription activator 1 in neuroblastoma cells ... 24 (6): 1407-12. doi:10.3892/ijo.24.6.1407 (inactive 2021-01-16). PMID 15138581.CS1 maint: DOI inactive as of January 2021 ( ... doi:10.1016/S0960-9822(02)00809-6. hdl:11858/00-001M-0000-0010-94EF-7. PMID 12007417. S2CID 7901788. Lagos-Quintana M, Rauhut R ...
Chemotherapy
Trilaciclib is an inhibitor of cyclin-dependent kinase 4/6 approved for the prevention of myelosuppression caused by ... For this reason the effect on the cell is dose dependent; the fraction of cells that die is directly proportional to the dose ... Unlike alkylating agents, anti-metabolites are cell cycle dependent. This means that they only work during a specific part of ... By contrast, other inhibitions of growth-signals like those associated with receptor tyrosine kinases are referred to as ...
MCM4
Ishimi Y, Komamura-Kohno Y (2001). "Phosphorylation of Mcm4 at specific sites by cyclin-dependent kinase leads to loss of Mcm4, ... This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase ... The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. ... A role for cdc2 kinase". J. Biol. Chem. 273 (27): 17095-101. doi:10.1074/jbc.273.27.17095. PMID 9642275. You Z, Komamura Y, ...
p21
cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase inhibitor 1A. External IDs. OMIM: 116899 MGI: 104556 HomoloGene: ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... 1994). "p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest ...
Cellular senescence
p16Ink4a also activates pRB, but through inactivation of cyclin-dependent kinase 4 (Cdk 4) and cyclin-dependent kinase 6 (Cdk 6 ... The p16 protein is a cyclin dependent kinase inhibitor (CDK) inhibitor and it activates Rb tumor suppressor. p16 binds to CDK 4 ... p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in ... The prolonged DDR activates both ATM and ATR DNA damage kinases. The phosphorylation cascade initiated by these two kinases ...
Protein crystallization
Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors". ...
Abemaciclib
... abemaciclib inhibits the enzymes cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6). These enzymes are ... This result suggest that there may be a mechanism of action other than inhibition of a cyclin-dependent kinase. After oral ... 111 (6): 2132-2145. doi:10.1111/cas.14419. PMC 7293084. PMID 32304130. LY2835219 Shows Strong Single-Agent Activity in ... a CDK4/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast ...
SAAL1
... along with mRNA Decay of Cyclin-dependent Kinase 6 Gene". International Journal of Molecular Sciences. 19 (12). doi:10.3390/ ... 8 (6): R173. doi:10.1186/ar2082. PMC 1794517. PMID 17109745. Saranya Revathy K, Umasuthan N, Whang I, Lee Y, Lee S, Oh MJ, Jung ... 122 (6): 957-68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923. "BoxShade ... 4 (6): 1633-49. doi:10.1002/pmic.200300771. PMID 15174133. S2CID 18810164. Gupta, R (2001). "Prediction of glycosylation sites ...
Trilaciclib
... may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin-dependent kinase 4/6, a ... a CDK 4/6 Inhibitor, in Extensive Stage Small Cell Lung Cancer (SCLC)" at ClinicalTrials.gov Clinical trial number NCT02499770 ... a CDK 4/6 Inhibitor, in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy" at ... for "Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung ...
Clb 5,6 (Cdk1)
Clb5 and Clb6 bind and activate Cdk1, and high levels of these cyclins are required for entering S-phase. S-phase cyclin ... G1/S cyclin-Cdk complexes promote the destruction of Sic1 and allow activation of Clb5- and Clb6-Cdk1 complexes. As the yeast ... In this hypothesis, cyclin concentrations must rise and accumulate to proceed to the next stage of the cell cycle. In mitotic ... Clb5 and Clb6 levels rise during G1 (earlier than other B-type cyclins) and stay high throughout S and M phases. During S-phase ...
ViroStatics
To this end, ViroStatics has focused on selectively targeting the Cyclin Dependent Kinases (CDKs) involved in these ... ViroStatics has discovered and is developing novel, highly potent inhibitors, which selectively target CDK4/6/9 in a single ... perturbations (CDK9 and CDK4/6). ViroStatics was formed In 2007 as a for-profit spin-off from the Research Institute for Human ...
Cell growth
These transitions are controlled by the cyclin-dependent kinase Cdk1.[6] Though the proteins that control Cdk1 are well ... a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. ... The protein kinase Cdr2 (which negatively regulates Wee1) and the Cdr2-related kinase Cdr1 (which directly phosphorylates and ... Wu L, Russell P (June 1993). "Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase". Nature. 363 (6431): 738-41. ...
Ribociclib
Cyclin-dependent kinases (CDKs) 4 and 6 are enzymes that have been shown to promote cell division and multiplication in both ... Ribociclib, sold under the brand name Kisqali,[1] is an inhibitor of cyclin D1/CDK4 and CDK6, and is used for the treatment of ... Conversely, drugs that induce CYP3A4, such as rifampicin and St John's Wort, can decrease ribociclib concentrations.[2][6] ... 16%). The drug also increases the QT interval and liver enzymes (alanine transaminase, aspartate transaminase).[2][6] ...
CDKN1A - Вікіпедія
cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase inhibitor 1A. Зовнішні ІД. OMIM: 116899 MGI: 104556 HomoloGene: ... cyclin-dependent protein kinase holoenzyme complex. • PCNA-p21 complex. • perinuclear region of cytoplasm. • клітинне ядро. • ... negative regulation of cyclin-dependent protein kinase activity. • transcription initiation from RNA polymerase II promoter. • ...
Mir-137
... 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 ...
CDKN2A
p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ... "CDKN2A cyclin dependent kinase inhibitor 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ... CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. ... "CDKN2A - Cyclin-dependent kinase inhibitor 2A - Homo sapiens (Human) - CDKN2A gene & protein". www.uniprot.org. Retrieved 2016- ...
Cyclin-dependent kinase 4
CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
CDK5R2
... , NCK5AI, P39, p39nck5ai, cyclin-dependent kinase 5, regulatory subunit 2 (p39), cyclin dependent kinase 5 regulatory ... cyclin-dependent protein kinase 5 activator activity. • lipid binding. Cellular component. • cytoplasm. • cyclin-dependent ... 2002). "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent ... positive regulation of protein kinase activity. • regulation of cyclin-dependent protein serine/threonine kinase activity. • ...
Dental pulp stem cells
... one being cyclin-dependent kinase 6 (CDK6), present in the dental pulp tissue. Additionally, DPSCs have displayed lower ... 29 (6): 532-9. doi:10.1016/S8756-3282(01)00612-3. PMID 11728923. Ching, H. S.; Luddin, N.; Rahman, I. A.; Ponnuraj, K. T. (2017 ... 4 (1): 21-6. doi:10.1007/s12015-008-9013-5. PMID 18300003. Onyekwelu, O; Seppala, M; Zoupa, M; Cobourne, MT (2007). "Tooth ... 6: 35. doi:10.1186/1479-5876-6-35. PMC 2529267. PMID 18598348. Nosrat, I; Widenfalk, J; Olson, L; Nosrat, CA (2001). "Dental ...
Androgen receptor
Cyclin D1, Cyclin-dependent kinase 7, DACH1, Death associated protein 6, L-DOPA, EFCAB6, Epidermal growth factor receptor, ... The AR acetylation site is a key target of NAD-dependent and TSA-dependent histone deacetylases and long non-coding RNA. More ... "Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)- ... Kim J, Jia L, Stallcup MR, Coetzee GA (February 2005). "The role of protein kinase A pathway and cAMP responsive element- ...
PPP2CA
Cyclin-dependent kinase 2, Cyclin-dependent kinase 6, FAM40A, IGBP1, MOBKL3, PPP2R1A, PPP2R1B, PPP2R2A, PPP2R3B, PPP2R5A, ... Cheng A, Kaldis P, Solomon MJ (Nov 2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C ... "Phosphorylation and activation of hamster carbamyl phosphate synthetase II by cAMP-dependent protein kinase. A novel mechanism ... Bennin DA, Don AS, Brake T, McKenzie JL, Rosenbaum H, Ortiz L, DePaoli-Roach AA, Horne MC (Jul 2002). "Cyclin G2 associates ...
Palbociclib
It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. In the G1 phase of the cell cycle, mammalian cells ... It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be ... 2009). "PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen ... breast tumor-related kinase). Brk is an intracellular kinase that is overexpressed in 60% of breast cancers and whose ...
PFKFB3
... increases proliferation via cyclin-dependent kinases". The Journal of Biological Chemistry. 284 (36): 24223-32. doi:10.1074/jbc ... and suppresses apoptosis by regulating cyclin-dependent kinase 1 (Cdk-1). PFKFB3's synthesis of F2,6BP in the nucleus was found ... Expression of the promoter is shown to be induce by phorbol esters and cyclic-AMP-dependent protein kinase signaling. The four ... due to phosphorylation of Ser-460 by PKA or AMP-dependent protein kinase. The high '2-Kase' activity of PFKFB3 is also due to ...
CDKL5
... is a gene that provides instructions for making a protein called cyclin-dependent kinase-like 5 also known as serine/ ... "Preclinical Program for Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency". Amicus Therapeutics Press Release. 6 July 2016. ... G40.42 Cyclin-dependent kinase Rett syndrome West syndrome GRCh38: Ensembl release 89: ENSG00000008086 - Ensembl, May 2017 ... The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of ...
Flavonoid alkaloid
Jain SK, Bharate SB, Vishwakarma RA (2012). "Cyclin-dependent kinase inhibition by flavoalkaloids". Mini Rev Med Chem. 12 (7): ... Bose P, Simmons GL, Grant S (2013). "Cyclin-dependent kinase inhibitor therapy for hematologic malignancies". Expert Opin ... One example is alvocidib, a potent CDK9 kinase inhibitor that is being developed for the treatment of chronic lymphocytic ... 26 (6): 1844-1845. doi:10.1016/S0031-9422(00)82304-3. Zhen, J., Dai, Y., Villani, T., Giurleo, D., Simon, J. and Wu, Q., 2017. ...
Histone
SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... "NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription". Genes & Development. 14 (18): ... The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... NPAT activates histone gene expression only after it has been phosphorylated by the G1/S-Cdk cyclin E-Cdk2 in early S phase.[ ...
Cell biology
The cell cycle is regulated by a series of signalling factors and complexes such as cyclin-dependent kinases and p53, to name a ... 6] Viruses range from 0.005 to .03 microns in size whereas Bacteria range from 1-5 microns.[7] Modern day cell biology research ...
p21, wolna encyklopedia
Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ... a b Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1). ... Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ...
Proteasome
Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that ... is one of the 19S subcomponents that also tightly binds the cyclin-dependent kinase CDK4 and plays a key role in recognizing ... In particular, exit from mitosis requires the proteasome-dependent dissociation of the regulatory component cyclin B from the ... the ATP-dependent proteolytic complex that was responsible for ubiquitin-dependent protein degradation was discovered and was ...
Aminoacyl tRNA synthetase
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ... 347 (6289): 203-6. doi:10.1038/347203a0. PMID 2203971.. *^ Cusack S (December 1997). "Aminoacyl-tRNA synthetases". Current ...
GTP-binding protein regulators
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ...
Linalol, wolna encyklopedia
... preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase ... Produkowany jest przez różne rodziny, m.in.: jasnotowate (bazylia[4], mięta[5]), wawrzynowate[6] (wawrzyn, cynamon) i rutowate ... Linalol (3,7-dimetylooktadi-1,6-en-3-ol) - organiczny związek chemiczny, nienasycony alkohol alifatyczny, należący do grupy ... InChI=1S/C10H18O/c1-5-10(4,11)8-6-7-9(2)3/h5,7,11H,1,6,8H2,2-4H3 ...
Mitosis
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ... Ramanathan SP, Helenius J, Stewart MP, Cattin CJ, Hyman AA, Muller DJ (February 2015). "Cdk1-dependent mitotic enrichment of ...
NMDA receptor
"Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation". Nature Neuroscience. 10 ( ... Src kinase enhances NMDA receptor currents.[98]. *Na+, K+ and Ca2+ not only pass through the NMDA receptor channel but also ... "MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term ... Depolarization of the cell dislodges and repels the Mg2+ and Zn2+ ions from the pore, thus allowing a voltage-dependent flow of ...
Intracranial aneurysm
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ... The inflammatory mediators are: Interleukin 1 beta, Interleukin 6, Tumor necrosis factor alpha (TNF alpha), MMP1, MMP2, MMP9, ... A ruptured microaneurysm may cause an intracerebral hemorrhage, presenting as a focal neurological deficit.[6] ... 6] Symptoms of a subarachnoid hemorrhage differ depending on the site and size of the aneurysm.[6] Symptoms of a ruptured ...
ডিএনএ অনুলিপন - উইকিপিডিয়া
"Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms"। Nature (ইংরেজি ভাষায়)। 411 (6841): 1068-1073 ... G1 ফেজ এর শেষের দিকে পরিবেশগত অবস্থা ঠিক থাকলে যেমন G1 এবং G1/S cyclin - Cdk কমপ্লেক্স সক্রিয় হয়, যা জিনের অভিব্যক্তিকে ... "CLB5-Dependent Activation of Late Replication Origins in S. cerevisiae"। Molecular Cell। 2 (2): 173-182। আইএসএসএন 1097-2765 ... ডিওআই:10.1016/s1097-2765(00)80127-6।. *↑ Aravind, L.; Leipe, Detlef D.; Koonin, Eugene V. (১৯৯৮-০৯-০১)। "Toprim-a conserved ...
Template:PBB/1026
cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ... Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • G2/M ...
Tat (HIV)
... 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.[21] ... of cellular CDK9 and cyclin T1, and hence increases the production of full-length viral RNA.[8] ...
Hsp70
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi: ... "The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C". The Journal of Biological ... When Hsp70 proteins are ADP bound, the lid is closed, and peptides are tightly bound to the substrate binding domain.[6] ...
CDH1 (gene)
Jiang MC, Liao CF, Tai CC (June 2002). "CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent ... The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a ...
GNB1
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
Apoptosis
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... the protein is cleaved by a calcium-dependent calpain protease ... "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Research. 149 (1 ...
Transferase
A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases. As their name implies ... "Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel ... CDKs are heavily dependent on specific cyclin molecules for activation. Once combined, the CDK-cyclin complex is capable of ... Herbst EA, MacPherson RE, LeBlanc PJ, Roy BD, Jeoung NH, Harris RA, Peters SJ (Jan 2014). "Pyruvate dehydrogenase kinase-4 ...
CDC42
GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... protein kinase binding. • nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
Factor de crecimiento transformante beta 1, la enciclopedia libre
... and the cyclin dependent kinase inhibitors P27 and P21.». Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/ ... de 2000). «Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of ... Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation». J ... La mayoría de las células inmunes (o leucocitos) secretan TGFB1.[6] TGF-β1 y células TEditar. Algunos tipos de células T, como ...
BRCA1
... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350.. ... "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): ... "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... 31 (6): 961-7. doi:10.1093/carcin/bgq069. PMID 20400477.. *^ a b c d e f g Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J ...
Amphiphysin
Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW (May 2002). "Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A ... Micheva KD, Ramjaun AR, Kay BK, McPherson PS (September 1997). "SH3 domain-dependent interactions of endophilin with ...
HIV bahasa Indonesia, ensiklopedia bebas
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase ... Int Rev Immunol. 6,163-75 PMID 2152500. *Learmont JC, Geczy AF, Mills J, Ashton LJ, Raynes-Greenow CH, Garsia RJ, Dyer WB, ... 6] Pada awal tahun 1984, Robert Gallo dari Amerika Serikat juga meneliti tentang virus penyebab AIDS yang disebut HTLV-III.[5][ ... 6] Bersama dengan Luc Montagnier, mereka membuktikan bahwa virus tersebut merupakan penyebab AIDS.[ ...
G protein
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... The cAMP-dependent pathway is used as a signal transduction pathway for many hormones including:. *ADH - Promotes water ... cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ...
Cyclin-dependent kinase 6 - Wikipedia
Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... "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 ... Liu, Ji; Kipreos, Edward T. (2000). "Evolution of Cyclin-Dependent Kinases (CDKs) and CDK-Activating Kinases (CAKs): ...
Cdk6 - Cyclin-dependent kinase 6 - Mus musculus (Mouse) - Cdk6 gene & protein
Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle ... Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ...
CDK6 - cyclin-dependent kinase 6 - Ursus maritimus (Polar bear) - CDK6 gene & protein
cyclin-dependent kinase 6Imported. Automatic assertion inferred from database entriesi ... tr,A0A384BPK8,A0A384BPK8_URSMA cyclin-dependent kinase 6 OS=Ursus maritimus OX=29073 GN=CDK6 PE=4 SV=1 ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR008271, Ser/Thr_kinase_AS. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR008271, Ser/Thr_kinase_AS. ...
Cyclin-Dependent Kinase 6
Summary Report | CureHunter
It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. ... Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE ... Protein Kinases: 9706*Protein-Serine-Threonine Kinases: 1353*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 6: 44*human ... Proline-Directed Protein Kinases: 26*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 6: 44*human CDK6 protein ...
Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer...
Cyclin-dependent kinase 6 (CDK6) binds to and is activated by cyclin D1 and thereby enhances the transition of cells through ... Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer ... Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer ... Cyclin-dependent kinase 6 associates with the androgen receptor and enhances its transcriptional activity in prostate cancer ...
RCSB PDB - 1XO2: Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin
Crystal Structure of a Human Cyclin-Dependent Kinase 6 Complex with a Flavonol Inhibitor, Fisetin.. Lu, H.S., Chang, D.J., ... Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. ... Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. ... Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. *DOI: 10.2210/pdb1XO2/pdb ...
A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis | Cancer Research
A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis. Miaofen G. Hu, Amit Deshpande, Miriam ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis ...
A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis | Cancer Research
Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J ... A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis. Miaofen G. Hu, Amit Deshpande, Miriam ... Cyclin-dependent kinase 6 (CDK6), a cyclin D-responsive regulator of the retinoblastoma protein (pRB) pathway, seems to be of ... Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal-nasopharyngeal NK/T-cell lymphomas: ...
RCSB PDB - 1GZ8: HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 2-Amino-6-(3'-methyl-2'-oxo)butoxypurine
HUMAN CYCLIN DEPENDENT KINASE 2 COMPLEXED WITH THE INHIBITOR 2-Amino-6-(3-methyl-2-oxo)butoxypurine. *DOI: 10.2210/pdb1GZ8/ ... Probing the ATP Ribose-Binding Domain of Cyclin-Dependent Kinases 1 and 2 with O(6)-Substituted Guanine Derivatives. Gibson, A. ... CELL DIVISION PROTEIN KINASE 2. A. 299. Homo sapiens. Mutation(s): 0 Gene Names: CDK2, CDKN2. EC: 2.7.1.37 (PDB Primary Data), ... competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. ...
Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology...
Cyclin-Dependent Kinase Inhibitor p21. *Cyclin-Dependent Kinase Inhibitor p27. *Cyclin-Dependent Kinases/antagonists & ... a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate tumor cells.. Mori S1, Murakami-Mori K, ... Western blot analysis showed that the protein levels of cyclin-dependent kinase-2 (CDK2), CDK4, and CDK6 were decreased, while ... In vitro kinase assays revealed that the CDK-associated histone H1 and CDK4- and CDK6-associated pRb kinase activities were ...
Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma...
One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kina … ... One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kinase that plays a vital role in cell cycle ... Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma ... or by inhibiting kinase function with a small molecule inhibitor, PD0332991. Cell proliferation was assessed by colony focus ...
Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated...
The PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), which shares extensive sequence homology (approximately 70%) with cdk4 ... Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated ... Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated ... Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated ...
Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts |...
Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res ... reduction of cyclin D expression through antisense technology causes a concomitant decline in cyclin D-dependent kinase ... Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nat Genet 2003;35:25-31. ... Cyclin-dependent kinase modulators studied at the NCI: pre-clinical and clinical studies. Curr Med Chem Anti-Canc Agents 2003;3 ...
Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts |...
Mitogen-activated protein kinase-activated protein kinase 1a. 8.0. Mitogen-activated protein kinase-activated protein kinase 2 ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts ... Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts ...
Interleukin-6 dependent induction of the cyclin dependent kinase inhibitor p21WAF1/CIP1 is lost during progression of human...
IL-6). This response is lost in cell lines derived from advanced lesions, a phenomenon which may contribute to tumor ... cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 ( ... which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex ... In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the ...
Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh - HER2 Support Group Forums
Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh Articles of Interest ... Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh ... Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh ... Re: Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 ...
Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell...
Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ... Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ... Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ... Correction to "Fisetin, an Inhibitor of Cyclin-Dependent Kinase 6, Down-Regulates Nuclear Factor-κB-Regulated Cell ...
Elevated activity of cyclin-dependent kinase 6 in human squamous cell carcinoma lines -- Timmermann et al. 8 (4): 361 -- Cell...
Elevated activity of cyclin-dependent kinase 6 in human squamous cell carcinoma lines. S Timmermann, PW Hinds and K Munger ... Expression of Cyclin-Dependent Kinase 6, but not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse Astrocytes. Mol ... Elevated activity of cyclin-dependent kinase 6 (cdk6), a pRB kinase, was detected in all five squamous cell carcinoma lines. ... Cyclin-Dependent Kinase 6 Inhibits Proliferation of Human Mammary Epithelial Cells. Mol. Cancer Res., February 1, 2004; 2(2): ...
Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or Serine/Threonine Protein Kinase PLSTIRE or CDK6 or EC 2.7.11.22) -...
Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or... ... Cell Division Protein Kinase 6 or Serine/Threonine Protein ... Kinase PLSTIRE or CDK6 or EC 2.7.11.22) - Pipeline Review, H2 2017 report by Global Markets Direct. ... 103 Pages Report] Check for Discount on Cyclin Dependent Kinase 6 ( ... Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or Serine/Threonine Protein Kinase PLSTIRE or CDK6 or EC 2.7.11.22) ...
Toll-like receptor 4 (TLR4) down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6
We have found that the putative miR-107 target cyclin-dependent-kinase 6 (CDK6) expression is increased by TLR4 as a result of ... Toll-like receptor 4 (TLR4) down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6. ... Toll-like receptor-4 (TLR4) down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6.pdf ( ... down-regulates microRNA-107 increasing macrophage adhesion via cyclin-dependent kinase 6, Journal of Biological Chemistry, 286 ...
Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin
Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription and neuronal functions. ... We describe here the crystal structure of human CDK6 in complex with a viral cyclin and a flavonol inhibitor, fisetin. Fisetin ... This complex structure is the first description of an inhibitor complex with a kinase from the CDK4/6 subfamily and can provide ... However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetine and flavopiridol showed a different ...
cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung...
cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ... Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ... cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ... cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) (abemaciclib , palbociclib , ribociclib) and interstitial lung ...
Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early...
Because cyclin-dependent kinase 4/6 (CDK4/6) inhibitors prevent G1/S transition, we hypothesized that serum TK1 could be a ... Thymidine kinase 1 (TK1) is a cell cycle-regulated enzyme with peak expression in the S phase during DNA synthesis, and it is ... and its value in predicting response to CDK4/6 inhibitors warrants further investigation. ClinicalTrials.gov, NCT01723774. ... biomarker for CDK4/6 inhibitors. We examined the drug-induced change in serum TK1 as well as its correlation with change in ...
Cyclin-dependent kinase - definition of Cyclin-dependent kinase by The Free Dictionary
Cyclin-dependent kinase synonyms, Cyclin-dependent kinase pronunciation, Cyclin-dependent kinase translation, English ... dictionary definition of Cyclin-dependent kinase. n. Any of various enzymes that catalyze the transfer of a phosphate group ... Cyclin-dependent kinase - definition of Cyclin-dependent kinase by The Free Dictionary https://www.thefreedictionary.com/Cyclin ... kinase. (redirected from Cyclin-dependent kinase). Also found in: Thesaurus, Medical, Acronyms, Encyclopedia, Wikipedia. ki· ...
Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively lethal to MYC-dependent human breast cancer...
We therefore investigated the therapeutic potential of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast ... MYC-dependent and MYC-independent cell lines were classified based on their sensitivity to siRNA-mediated MYC knockdown. We ... An alternative approach is to identify genes that are synthetically lethal in MYC-dependent cancer. Recent studies have ... Overall, these results suggest that further investigation of CDK1 inhibition as a potential therapy for MYC-dependent breast ...
1bi7.1 | SWISS-MODEL Template Library
MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX ... MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX. ... Russo, A.A. et al., Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. ... CYCLIN-DEPENDENT KINASE 6: AC. MULTIPLE TUMOR SUPPRESSOR: BD. SMTL:PDB. SMTL Chain Id:. PDB Chain Id:. A. A ...
CDK11B cyclin dependent kinase 11B [Homo sapiens (human)] - Gene - NCBI
CDK11B cyclin dependent kinase 11B [Homo sapiens] CDK11B cyclin dependent kinase 11B [Homo sapiens]. Gene ID:984 ... cyclin-dependent kinase 11B. Names. CDC-related protein kinase p58. PITSLRE serine/threonine-protein kinase CDC2L1. cell ... Title: Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets ... cyclin dependent kinase 11Bprovided by HGNC. Primary source. HGNC:HGNC:1729 See related. Ensembl:ENSG00000248333 MIM:176873 ...
What are Cyclin-Dependent Kinases?
Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... Cyclin Dependent Kinases in the Cell Cycle. Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene ... Control of Cyclin Dependent Kinases. Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, ...
Cyclin-Dependent Kinase 9 (CDK9) Inhibitor -Pipeline Insight, 2018
Table 2: Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Therapeutic Products in Clinical Stages. Table 3: Cyclin-Dependent Kinase 9 ... Figure 2: Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Therapeutic Products in Clinical Stages. Figure 3: Cyclin-Dependent Kinase ... 2. Cyclin-Dependent Kinase 9 (CDK9) Inhibitor - Overview. 3. Pipeline Therapeutics*An Overview of Pipeline Products for Cyclin- ... Dependent Kinase 9 (CDK9) Inhibitor 4. Comparative Analysis. 5. Cyclin-Dependent Kinase 9 (CDK9) Inhibitor Pipeline Products in ...
MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer
Cyclin-dependent kinase 6. CDKN:. Cyclin-dependent kinase inhibitor. c-Kit:. v-kit Hardy-Zuckerman 4 feline sarcoma viral ... phosphatidylinositol-3-kinase regulatory subunit beta, PI3K. ) mRNA and modulates its expression. PI3K. is a regulatory subunit ... H. Sakai, A. Sato, Y. Aihara et al., "MKK7 mediates miR-493-dependent suppression of liver metastasis of colon cancer cells," ... 16], both of them were able to directly modulate the expression of DAPK1 (death-associated protein kinase 1) and KLF4 (Krüppel- ...
CDK6InhibitorsCDKsInhibitionCDK2GenePhosphorylationProgressionRetinoblastomaRibociclibPalbociclibCDK1Proteins2018TumorGenesInducesDual inhibitorPhosphorylatesTargetsEpidermal growth fAbemaciclibVerzenioInteractsEarly G1 phaseRegulationInhibitsMutationsCancerMitogen-activaActivityProto-oncogeneLymphomaExpressionPhosphatidylinositol 3-kinaCancersCellsTumorsHumanEnzymeBindsTargetingIbrance
CDK645
- Cell division protein kinase 6 (CDK6) is an enzyme encoded by the CDK6 gene. (wikipedia.org)
- This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor Retinoblastoma protein making CDK6 an important protein in cancer development. (wikipedia.org)
- In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. (wikipedia.org)
- However, in recent years, new evidence proved that the presence of CDK6 is not essential for proliferation in every cell type, the cell cycle has a complex circuitry of regulation and the role of CDK6 might be more important in certain cell types than in others, where CDK4 or CDK2 can act as protein kinases compensating its role. (wikipedia.org)
- There are additional functions of CDK6 not associated with its kinase activity. (wikipedia.org)
- Cyclin-dependent kinase 6 (CDK6) binds to and is activated by cyclin D1 and thereby enhances the transition of cells through the G 1 phase of the cell cycle. (pnas.org)
- This effect of CDK6 does not require its kinase activity and is inhibited by cyclin D1 and p16 INK4a . (pnas.org)
- We also show that this effect is independent of cyclin D1 and CDK6 kinase activity. (pnas.org)
- We describe here the crystal structure of human CDK6 in complex with a viral cyclin and a flavonol inhibitor, fisetin. (rcsb.org)
- Fisetin binds to the active form of CDK6, forming hydrogen bonds with the side chains of residues in the binding pocket that undergo large conformational changes during CDK activation by cyclin binding. (rcsb.org)
- Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. (aacrjournals.org)
- Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. (aacrjournals.org)
- These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies. (aacrjournals.org)
- Cyclin-dependent kinase 6 (CDK6), a cyclin D-responsive regulator of the retinoblastoma protein (pRB) pathway, seems to be of central importance in T-cell development. (aacrjournals.org)
- The activity of CDK6 is very tightly controlled by association with D-cyclins ( 7 ) and two families of CDK inhibitors, including the CIP/KIP family and the inhibitors of CDK4 (INK4) family proteins ( 9 ). (aacrjournals.org)
- In contrast, cyclin D2 expression is high in the DN1-DN3 stages before pre-TCR assembly and barely detectable after pre-TCR assembly ( 10 ), suggesting that CDK6 may use different cyclin partners in the thymocyte developmental stages. (aacrjournals.org)
- Consistent with a key role for CDK6 as a D-cyclin partner in thymocytes, knockout (KO) of CDK4 or CDK2 was shown to have no significant effect on T-cell development ( 11 , 12 ), but significantly decreased thymic cellularity was observed in a CDK6 KO animal ( 13 ). (aacrjournals.org)
- Following IL-6 treatment of LNCaP, Western blot analysis showed that the protein levels of cyclin-dependent kinase-2 (CDK2), CDK4, and CDK6 were decreased, while accumulation of CDK inhibitor p27(Kip1) was rapidly and markedly induced. (nih.gov)
- In vitro kinase assays revealed that the CDK-associated histone H1 and CDK4- and CDK6-associated pRb kinase activities were significantly inhibited in IL-6-treated LNCaP. (nih.gov)
- One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kinase that plays a vital role in cell cycle progression and differentiation. (nih.gov)
- To investigate the role of CDK6 in medulloblastoma, we assayed the effect of CDK6 inhibition on proliferation by depleting expression with RNA interference (RNAi) or by inhibiting kinase function with a small molecule inhibitor, PD0332991. (nih.gov)
- Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated cdk4 homologue in normal human T lymphocytes. (jimmunol.org)
- The PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), which shares extensive sequence homology (approximately 70%) with cdk4, was identified as the earliest inducible member of the cdk family of proteins in human T lymphocytes induced to proliferate in vitro by stimulation either with phorbol 12,13-dibutyrate and ionomycin (PDB/I) or PHA. (jimmunol.org)
- Furthermore, increased accumulation of p40cdk6 protein and activity occurred in cells rendered "competent" (responsive to IL-2) by a brief treatment with PDB/I. Thus, increased accumulation of the protein and its activity begin before IL-2/IL-2 receptor interaction, suggesting that the cdk6-cyclin D2 complex might be involved in acquisition of the competent state in human T lymphocytes. (jimmunol.org)
- PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC 50 , 0.011 μmol/L) and Cdk6 (IC 50 , 0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. (aacrjournals.org)
- Progression through the G 1 -S phase requires phosphorylation of the retinoblastoma (Rb) protein by Cdk4 ( 7 , 8 ) or the highly homologous enzyme Cdk6 ( 9 , 10 ) in complex with their activating subunits, the D-type cyclins, D1, D2, or D3 ( 11 ). (aacrjournals.org)
- Elevated activity of cyclin-dependent kinase 6 (cdk6), a pRB kinase, was detected in all five squamous cell carcinoma lines. (aacrjournals.org)
- The latest report Cyclin Dependent Kinase 6 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or Serine/Threonine Protein Kinase PLSTIRE or CDK6 or EC 2.7.11.22) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportsnreports.com)
- Furthermore, this report also reviews key players involved in Cyclin Dependent Kinase 6 (Cell Division Protein Kinase 6 or Serine/Threonine Protein Kinase PLSTIRE or CDK6 or EC 2.7.11.22) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsnreports.com)
- We have found that the putative miR-107 target cyclin-dependent-kinase 6 (CDK6) expression is increased by TLR4 as a result of the decrease in miR-107. (tcd.ie)
- Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a. (expasy.org)
- Levels of cyclin-dependent kinase 1 (CDK1) and CDK6, Bcl2 and BAX and cytochrome c were quantified by specific ELISA. (who.int)
- Cyclin-dependent kinase 6 (CDK6) bound to the inhibitor ribociclib (detail view). (news-medical.net)
- Abemaciclib is an antitumor agent and dual inhibitor of cyclin-dependent kinases 4 (CDK4) and 6 (CDK6) that are involved in the cell cycle and promotion of cancer cell growth in case of unregulated activity. (drugbank.ca)
- RT "Identification of G1 kinase activity for cdk6, a novel cyclin D RT partner. (genome.jp)
- RT "Transforming activity of Fbxo7 is mediated specifically through RT regulation of cyclin D/cdk6. (genome.jp)
- RT "Preferences for phosphorylation sites in the retinoblastoma protein RT of D-type cyclin-dependent kinases, Cdk4 and Cdk6, in vitro. (genome.jp)
- The present study indicated that cyclin‑dependent kinase 6 (CDK6) was the direct target gene of miR‑25 using mRNA and protein expression analysis, and luciferase assays. (spandidos-publications.com)
- In the current study, it was hypothesized that the expression of miR-25 was inhibited in TNF-α-stimulated VSMCs and that overexpression of miR-25 in the VSMCs inhibited cell proliferation by targeting cyclin-dependent kinase 6 (CDK6). (spandidos-publications.com)
- This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. (genecards.org)
- Prior to G1 phase, levels of Cdk4 and Cdk6 increase along with cyclin D. This allows for the partial phosphorylation of Rb, and partial activation of E2F at the beginning of G1 phase, which promotes cyclin E synthesis and increased Cdk2 activity. (wikipedia.org)
- The transition through G1 to S phase is regulated by cyclins, cyclin-dependent kinases (CDK)-CDK4 and CDK6 and their inhibitors. (thefreedictionary.com)
- Some CDKs, such as CDK1-CDK4, CDK6 and perhaps CDK11, are involved in progression through the cell cycle, whereas CDK7 has dual roles as a CDK-activating kinase (CAK) and a regulator of the transcriptional machinery. (thefreedictionary.com)
- Indianapolis, Indiana-based global pharmaceuticals specialist Eli Lilly and Company's (NYSE: LLY) Phase 3 JUNIPER study evaluating Verzenio (abemaciclib), a cyclin-dependent kinase 4 and CDK6 inhibitor, as monotherapy in KRAS-mutated, advanced non-small lung cancer (NSCLC) did not meet its primary endpoint of overall survival (OS), the company said. (thefreedictionary.com)
- The two cell-cycle kinases CDK4 and CDK6 normally facilitate cell-cycle progression but are abnormally activated in certain cancers. (thefreedictionary.com)
Inhibitors26
- the cyclin D. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (wikipedia.org)
- The 4-keto group and the 3-hydroxyl group of fisetin are hydrogen bonded with the backbone in the hinge region between the N-terminal and C-terminal kinase domain, as has been observed for many CDK inhibitors. (rcsb.org)
- However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees. (rcsb.org)
- O(6)-substituted guanines are adenosine 5'-triphosphate (ATP) competitive inhibitors of CDK1/cyclin B1 and CDK2/cyclin A, the O(6) substituent occupying the kinase ribose binding site. (rcsb.org)
- and expression, degradation, and availability of naturally occurring protein inhibitors and subcellular localization of these various regulatory components ( 2 , 5 , 6 ). (aacrjournals.org)
- With the combo of Palbociclib plus the estrogen inhibitor it 20 months time to progression.This seems pretty dramatic evidence pointing to the fact that CyclinD 4/6 inhibitors are extremely effective drugs. (her2support.org)
- Of the 3 commonly used CDK-4,6 inhibitors, Abemicliclib or versenio seems to have less severe neutropenia. (her2support.org)
- Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (thefreedictionary.com)
- p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (thefreedictionary.com)
- Some of the non-biological drugs, known as Cyclin-dependent kinase (CDK) inhibitors, are currently being tested for use in cancer treatment. (thefreedictionary.com)
- Altered prostatic epithelial proliferation and apoptosis, prostatic development and serum testosterone in mice lacking cyclin-dependent kinase inhibitors," Biology of Reproduction 73(5): 951-958. (thefreedictionary.com)
- We then inhibited CDKs including CDK4/6, CDK2 and CDK1 individually using either RNAi or small molecule inhibitors, and compared sensitivity to CDK inhibition with MYC dependence in breast cancer cells. (biomedcentral.com)
- 4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6. (astx.com)
- Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, thereby preventing the cell cycle from being driven forward. (news-medical.net)
- PI3 kinase inhibitors are a class of drugs designed to interrupt PI3 kinase signals and stop the growth of cancer cells. (komen.org)
- CDK4/6 inhibitors are a class of drugs designed to interrupt the growth of cancer cells. (komen.org)
- Abemaciclib (Verzenio) , palbociclib (Ibrance) and ribociclib (Kisqali) are CDK4/6 inhibitors FDA-approved for metastatic breast cancer treatment. (komen.org)
- The Kinase Enzyme Systems allow you to easily screen and profile kinase inhibitors. (promega.com)
- In addition, tamoxifen, which is commonly used in premenopausal patients, has not been tested in combination with any of the CDK4/6 inhibitors like Kisqali or Ibrance. (breastcancer.org)
- G 1 CDK2 and CDK4 kinase activities were increased in both normal and neoplastic tissues derived from mice lacking individual CDK inhibitors and were synergistically stimulated by the simultaneous loss of two CDK inhibitors. (asm.org)
- Two families of cyclin-dependent kinase (CDK) inhibitors, totaling seven genes, have been identified in mammalian cells. (asm.org)
- Indeed, the only nuclear G1/S molecules are the cell cycle inhibitors, pRb, p57, and variably, p21: none of the cyclins or cdks necessary to drive human β-cell proliferation are present in the nuclear compartment. (diabetesjournals.org)
- We have also investigated the geldanamaycins, small-molecule inhibitors of hsp90, a cellular chaperone required for the proper folding of multiple kinases, including cdk4. (dana-farber.org)
- Hsp90 inhibition may represent a promising strategy for EGFR mutant lung cancers that have acquired resistance to standard tyrosine kinase inhibitors.Another active area of investigation is in regulation of Aurora kinases, mitotic kinases that are frequently dysregulated in cancer. (dana-farber.org)
- Cyclin-dependent kinase (CDK) 4/6 inhibitors have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. (medworm.com)
- The aim of this article is to give a short overview of the existing efficacy data, to summarize the recommended clinical monitoring procedures for patients under CDK4/6 inhibitors, and to shed light on the clinical management of the most common treatment-emergent adverse even. (medworm.com)
CDKs8
- Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. (rcsb.org)
- Our results show that IL-6 treatment of early stage melanoma cell lines caused G1 arrest, which could not be explained by changes in levels of G1 cyclins (D1, E), cdks (cdk4, cdk2) or by loss of cyclin/cdk complex formation. (nih.gov)
- Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. (yonsei.ac.kr)
- These cyclins oscillate, increasing and decreasing at different stages, binding to CDKs and driving the cell cycle forward. (news-medical.net)
- In addition to cyclin levels, this provides and additional way to control the activity of CDKs. (news-medical.net)
- Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. (dana-farber.org)
- During cell-cycle progression, D-cyclins activate cyclin-dependent kinases (CDKs) 4/6 to inactivate Rb, permitting E2F1-mediated S-phase gene transcription. (aacrjournals.org)
- At the cellular level, the process is controlled by different levels of cyclin-dependent kinases (Cdks) and their partner cyclins. (wikipedia.org)
Inhibition15
- The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors. (aacrjournals.org)
- Experimental evidence suggests that inhibition of cyclin D-dependent kinase activity may prevent tumor growth and/or at least partially revert the transformed phenotype. (aacrjournals.org)
- For example, reduction of cyclin D expression through antisense technology causes a concomitant decline in cyclin D-dependent kinase activity and results in inhibition of tumor growth, abolition of tumorigenicity, or, in some instances, tumor cell death ( 24 -27 ). (aacrjournals.org)
- Therapeutically active doses of PD 0332991 in vivo cause down-regulation of proteins and genes in tumor tissue that are consistent with inhibition of Cdk4/6. (aacrjournals.org)
- We sought to determine whether resistance to growth inhibition by IL-6 can be explained by oncogenic alterations in cell cycle regulators or relevant components of intracellular signaling. (nih.gov)
- Thus, our results suggest that in early stage human melanoma cells, IL-6 induced growth inhibition involves induction of p21WAF1/CIP1 which is lost in the course of tumor progression presumably as a result of a dominant oncogenic event. (nih.gov)
- We therefore investigated the therapeutic potential of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast cancer. (biomedcentral.com)
- Overall, these results suggest that further investigation of CDK1 inhibition as a potential therapy for MYC-dependent breast cancer is warranted. (biomedcentral.com)
- Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel. (nih.gov)
- Vol 7: PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis. (duhnnae.com)
- Retinoblastoma protein (Rb) usually functions to inhibit the transcription factor E2F, however, when cyclin-D-CDK4 phosphorylates the Rb protein, this relinquishes inhibition of E2F and leads to the production of genes required for entering the S phase. (news-medical.net)
- During the course of this work, we discovered that lung cancer cell lines harboring kinase domain mutations of epidermal growth factor receptor (EGFR) were the most sensitive to hsp90 inhibition, and we have defined mutant EGFR as a novel hsp90 client protein that is rapidly depleted following geldanamycin treatment. (dana-farber.org)
- This work represents a first step toward defining tumors that are more likely to respond to Aurora kinase inhibition. (dana-farber.org)
- Inhibits cell cycle progression via inhibition of CDK4 kinase. (springer.com)
- Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts. (ucsf.edu)
CDK29
- Cell cycle arrest induced by MYC knockdown was accompanied by a decrease in CDK2 activity, but inactivation of CDK2 did not selectively affect the viability of MYC-dependent breast cancer cells. (biomedcentral.com)
- Cyclin A is also produced, which binds to CDK2 and stimulates DNA replication. (news-medical.net)
- A dominant-negative Cdc2 mutant arrested cells at the G2 to M phase transition, whereas mutants of the cyclin-dependent kinases Cdk2 and Cdk3 caused a G1 block. (sciencemag.org)
- Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the CDK2 gene. (wikipedia.org)
- This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. (wikipedia.org)
- Cdk2 is capable of binding to many different cyclins, including cyclins A, B, E, and possibly C. Recent studies suggest Cdk2 binds preferentially to cyclins A and E, while Cdk1 prefers cyclins A and B. Cdk2 becomes active when a cyclin protein (either A or E) binds at the active site located between the N and C lobes of the kinase. (wikipedia.org)
- Due to the location of the active site, partner cyclins interact with both lobes of Cdk2. (wikipedia.org)
- Cdk2 contains an important alpha helix located in the C lobe of the kinase, called the C-helix or the PSTAIRE-helix. (wikipedia.org)
- It is important to note that throughout this activation process, cyclins binding to Cdk2 do not undergo any conformational change. (wikipedia.org)
Gene21
- The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
- The gene spans 231,706 base pairs and encodes a 326 amino acid protein with a kinase function. (wikipedia.org)
- Activity of the kinase, determined by in vitro phosphorylation of recombinant truncated retinoblastoma tumor suppressor gene (Rb) protein (p60Rb), paralleled p40cdk6 protein amounts. (jimmunol.org)
- The miR-107 sequence occurs in an intron within the sequence encoding the gene for Pantothenate kinase-1? (tcd.ie)
- This gene encodes a member of the serine/threonine protein kinase family. (nih.gov)
- The protein kinase encoded by this gene can be cleaved by caspases and may play a role in cell apoptosis. (nih.gov)
- The differences at each stage are due to a balance between the gene expression of each cyclin and the ubiquitin-proteasome system which breaks them down. (news-medical.net)
- Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene expression, which binds to CDK4. (news-medical.net)
- The PIK3CA gene helps control PI3 kinase enzyme activity. (komen.org)
- The PI3 kinase inhibitor alpelisib (Piqray) is FDA-approved for the treatment of some metastatic breast cancers that have a PIK3CA gene mutation. (komen.org)
- Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene . (wikipedia.org)
- The protein encoded by this gene is a member of the Ser/Thr protein kinase family . (wikipedia.org)
- This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (wikipedia.org)
- Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
- Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene . (wikipedia.org)
- The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. (wikipedia.org)
- Gene that encodes cyclin A1. (springer.com)
- CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) is a Protein Coding gene. (genecards.org)
- GO annotations related to this gene include protein kinase binding and cyclin-dependent protein serine/threonine kinase inhibitor activity . (genecards.org)
- The discovery of mutations in the α-synuclein gene, which encodes the main protein misfolded in PD aggregates, together with mutations in genes encoding ubiquitin regulatory molecules, including PTEN-induced kinase 1 (PINK1), Parkin, and FBX07, has provided an opportunity to dissect out the molecular basis of ubiquitin signalling disruption in PD, and this knowledge will be critical for developing novel therapeutic strategies in PD that target the ubiquitin system. (biochemj.org)
- This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, also known as Cdk1 in humans. (wikipedia.org)
Phosphorylation5
- This protein also contains an ATP-binding pocket, inhibitory and activating phosphorylation sites, a PSTAIRE-like cyclin-binding domain and an activating T-loop motif. (wikipedia.org)
- After binding the Cyclin in the PSTAIRE helix, the protein changes its conformational structure to expose the phosphorylation motif. (wikipedia.org)
- Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. (yonsei.ac.kr)
- LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as FOXM1, Cyclin A1, and Myc in ATC. (yonsei.ac.kr)
- Silencing of APE1 attenuated cyclin D1/cyclin-dependent kinase 4 expression and phosphorylation of ERK1/2 and Akt, thereby affecting keratinocyte proliferation. (jimmunol.org)
Progression5
- It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
- Associated with cyclin-D, CDK4 phosphorylates and inactivates retinoblastoma (Rb) protein family members and mediates progression through the G1- to the S-phase of the cell cycle. (springer.com)
- This leads to increased expression of downstream signalling molecules and activity of protein kinases that promote the cell cycle progression and initiation of DNA replication. (drugbank.ca)
- Dominant-negative mutations were used to address the requirement for kinases of this family in progression through the human cell cycle. (sciencemag.org)
- Serine/threonine kinases that promote cell cycle progression. (springer.com)
Retinoblastoma4
- Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (curehunter.com)
- This article is from Oncology Letters, volume 7.AbstractPreclinical and clinical studies have demonstrated the anticancer activity of PD-0332991, a selective cyclin-dependent kinase 4-6 CDK4-6 inhibitor, in the treatment of various types of cancer in a retinoblastoma protein RB-dependent manner. (duhnnae.com)
- [5] Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
- We have demonstrated the depletion of cdk4 in lung cancer cell lines treated with geldanamycins, an effect that induces retinoblastoma-dependent G1 arrest. (dana-farber.org)
Ribociclib4
- However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. (yonsei.ac.kr)
- Ribociclib is a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. (medscape.com)
- These results affirm that combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer," said Gabriel N. Hortobagyi, MD, from the University of Texas MD Anderson Cancer Center in Houston and a MONALEESA-2 principal investigator, in the statement. (medscape.com)
- NVS ) CDK4/6 inhibitor ribociclib (Kisqali) for advanced breast cancer. (xconomy.com)
Palbociclib3
- This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. (elsevier.com)
- Ibrance capsules for oral administration contain 125 mg, 100 mg, or 75 mg of palbociclib, a kinase inhibitor. (rxlist.com)
- PFE ) drug palbociclib (Ibrance) was the first CDK4/6 inhibitor to reach the market, approved by the FDA in 2015 to treat advanced breast cancer. (xconomy.com)
CDK11
- In contrast, CDK1 inactivation significantly induced apoptosis and reduced viability of MYC-dependent cells but not MYC- independent cells. (biomedcentral.com)
Proteins9
- It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. (wikipedia.org)
- Importantly, these C-CDK complexes act as a kinase, phosphorylating and inactivating the protein of Rb and p-Rb related "pocket proteins" p107 and p130. (wikipedia.org)
- In contrast, IL-6 failed to induce p21WAF1/CIP1 transcript and did not increase p21WAF1/CIP1 or p27kip1 proteins in any of the resistant lines. (nih.gov)
- Once bound to a cyclin they act to phosphorylate many target proteins on serine or threonine amino acid residues. (news-medical.net)
- Each interacts with a different cyclin at a different phase, stimulating various target proteins and ensuring that vital stages of each phase are carried out before a cell moves onto the next phase. (news-medical.net)
- The myeloma drug lenalidomide promotes the cereblon-dependent destruction of ikaros proteins. (nature.com)
- Borne out of motivation to better understand the nature of protein degradation, pioneering studies elucidated a multistep ATP-dependent enzymatic cascade by which ubiquitin is conjugated to proteins, marking them for degradation [ 7 ]. (biochemj.org)
- METHODS: We studied how two structurally distinct forms of type I collagen, monomer versus polymerized fibrils, affect cell proliferation, mitogen-activated protein kinase (MAPK) activation, and expression of G1-phase regulatory proteins in cultured rat mesangial cells (MCs). (biomedsearch.com)
- It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. (wikipedia.org)
20182
- 30(6):385-391, December 2018. (lww.com)
- 2018;5(5-6):137-139. (mdanderson.org)
Tumor5
- In this context, miRNAs can play a functionality of either tumor suppressors or oncogenes (oncomirs) [ 6 ]. (hindawi.com)
- This mutation can affect PI3 kinase and cause the tumor to grow. (komen.org)
- This indicates that an increase in G 1 CDK kinase activity is a critical step during but is not sufficient for tumor growth. (asm.org)
- Conceptually, genes that negatively regulate the growth-suppressing activity of either p53 or pRb may be proto-oncogenes, as exemplified by the observation that MDM2 ( 26 ) and cyclin D1 ( 20 ), negative regulators of p53 and pRb, respectively, are frequently activated in human cancers and promote tumor growth when targeted for transgenic expression in mouse mammary tissues ( 22 , 35 ). (asm.org)
- The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. (aacrjournals.org)
Genes5
- An alternative approach is to identify genes that are synthetically lethal in MYC-dependent cancer. (biomedcentral.com)
- Recent studies have identified several cell cycle kinases as MYC synthetic-lethal genes. (biomedcentral.com)
- Consequently, an alternative approach which has recently received great attention is to identify genes that are synthetically lethal in MYC-dependent cancers. (biomedcentral.com)
- These genes include cyclin E, which binds to CDK4, driving the cell cycle into the S phase. (news-medical.net)
- The presence of two families of seven distinct mammalian cyclin-dependent kinase (CDK) inhibitor genes is thought to mediate the complexity of connecting a variety of cellular processes to the cell cycle control pathway. (asm.org)
Induces3
- Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin-dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate t. (nih.gov)
- IL-6 induces G1 growth arrest of LNCaP. (nih.gov)
- We have shown that the Aurora kinase inhibitor VX-680 induces endoreduplication and eventual cell death in cancer cells. (dana-farber.org)
Dual inhibitor1
- Ukoniq (umbralisib) is a dual inhibitor of phosphoinositide 3 kinase (PI3K). (drugs.com)
Phosphorylates1
- Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
Targets2
- APC/C then drives the process forward as it subsequently targets Ase1 and cyclin B for destruction ( Peters 1999 ). (rupress.org)
- is a human monoclonal antibody that targets the interleukin-6 receptor and is licensed for the treatment of moderate to severe active rheumatoid arthritis. (medicinescomplete.com)
Epidermal growth f1
- HER2 is a transmembrane glycoproteins epidermal growth factor receptor (EGFR) with Tyrosine kinase activity. (brainscape.com)
Abemaciclib1
- Abemaciclib with continuous dosing v.s 3 weeks on 1 off for the others CDK4/6, abemaciclib does have less severe neutropenia. (her2support.org)
Verzenio1
- Verzenio is a cyclin-dependent kinase (CDK)4 & 6 inhibitor that will be available as 50, 100, 150 and 200 mg tablets. (thefreedictionary.com)
Interacts2
- Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. (uniprot.org)
- Interacts with D-type G1 cyclins. (abcam.com)
Early G1 phase1
- Cyclins D2 and D3 were the major cyclins associated with p40cdk6, with D2 predominating in early G1 phase. (jimmunol.org)
Regulation3
- The redox-dependent action of APE1 may be involved in the regulation of gastric inflammation ( 5 ), LPS-mediated inducible NO synthase ( 6 ), and high-mobility group box (HMGB) 1-induced inflammatory responses ( 7 ). (jimmunol.org)
- Coordinates cell division via regulation of cyclin-dependent kinases. (springer.com)
- The success of the cell division process is dependent on the precise regulation of processes at both cellular and tissue levels. (wikipedia.org)
Inhibits2
- In addition to its role in cell cycle control, cyclin D1 also binds to and activates the estrogen receptor ( 11 ) but binds to and inhibits the activity of the AR ( 12 , 13 ). (pnas.org)
- it inhibits the cyclin-dependent kinase (CDK) 4 and 6. (medindia.net)
Mutations1
- The first mechanism is based on increased androgen receptor signaling caused by mutations in the AR that allow it to be activated by ligands other than DHT or by signaling pathways induced by a tyrosine kinase receptor, such as Her/2neu ( 5 , 6 ). (pnas.org)
Cancer13
- The frequency of these alterations alone clearly implies that abrogation of the G 1 checkpoint or acceleration of the Cdk4/cyclin D pathway provides a distinct advantage to cancer cells in terms of proliferation and perhaps survival. (aacrjournals.org)
- Based on these observations, cyclin D-dependent kinases have been considered for many years a prime target for cancer chemotherapy ( 22 , 23 ). (aacrjournals.org)
- These observations lend credence to Cdk4/6 as a target for cancer treatment and allow a reasonable expectation that a specific inhibitor of these enzymes would produce a meaningful therapeutic response. (aacrjournals.org)
- Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. (thefreedictionary.com)
- The report provides a competitor evaluation in the field of synthetic molecules targeting polo-like kinase 1 (Plk-1), cyclin-dependent kinase (CDK) or aurora kinase for treatment of cancer as of September 2011. (thefreedictionary.com)
- Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer. (yonsei.ac.kr)
- Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER + ) breast cancer. (elsevier.com)
- We will finally discuss how studies on phosphatidylinositol-3-kinase (PI3K) signalling, as the paradigmatic pro-tumoural signal downstream of oncogenic Kras in pancreatic cancer, would benefit from exploratory proteomics to increase the efficiency of targeted therapies. (mdpi.com)
- The study was presented on Dec. 6, 2017 at the 2017 San Antonio Breast Cancer Symposium. (breastcancer.org)
- It would only be for patients with cancer that does not depend on the CDK4/6 enzymes. (xconomy.com)
- Cytoplasmic Cyclin E Expression Predicts for Response to Neoadjuvant Chemotherapy in Breast Cancer. (mdanderson.org)
- The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines. (aacrjournals.org)
- Liver cancer is ranked in the top 10 human cancers worldwide and among the top five of cancers in terms of mortality [ 5 , 6 , 7 ]. (mdpi.com)
Mitogen-activa1
- As one example, we have only recently learned that loss of the platelet-derived growth factor (PDGF) receptor-α in adult human β-cells, with the resultant loss of ability to activate mitogen-activated protein kinase and methylation (Ezh2) and downstream cell cycle (p16) machinery, may underlie the refractoriness of human β-cells to proliferation ( 16 ). (diabetesjournals.org)
Activity7
- It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (curehunter.com)
- Elevated activity of cyclin-dependent kinase 6 in human squamous cell carcinoma lines -- Timmermann et al. (aacrjournals.org)
- CDK11(p58) kinase activity is required to protect sister chromatid cohesion at centromeres in mitosis. (nih.gov)
- The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16 INK4a . (wikipedia.org)
- Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
- We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression. (aacrjournals.org)
- Moreover, polymerized type I collagen markedly reduced cyclin E-associated kinase activity in the presence of 5% FCS. (biomedsearch.com)
Proto-oncogene1
- BRAF, B-Raf proto-oncogene, serine/threonine kinase. (thefreedictionary.com)
Lymphoma3
- Mantle cell lymphoma (MCL), characterized by elevated cyclin D1, was used as a model to test this approach. (aacrjournals.org)
- is an inhibitor of Bruton's tyrosine kinase used in mantle cell lymphoma. (medicinescomplete.com)
- is a phosphoinositide-3 kinase (PI3K) inhibitor that is licensed for the treatment of relapsed follicular lymphoma. (medicinescomplete.com)
Expression4
- Ruiling Zhang and team from Xinxiang Medical University explored the correlation between cyclin-dependent kinase 5 expression in the hippocampus and neurological impairments following prenatal ethanol exposure, and found that prenatal ethanol exposure could affect cyclin-dependent kinase 5 and its activator p35 in the hippocampus of offspring rats. (thefreedictionary.com)
- Real-time RT-PCR demonstrated that the expression of the cell cycle-driving molecule, cyclin-dependent kinase 4 (Cdk4), in HCC was significantly reduced by the treatments with vitamin K2, K3 and K5. (thefreedictionary.com)
- Importantly, TLR2-induced generation of reactive oxygen species contributed to the nuclear translocation and expression of APE1, suggesting an autoregulatory circuit in which the subcellular localization of APE1 is associated with the production of APE1 per se through reactive oxygen species-dependent signaling. (jimmunol.org)
- Protein expression of cyclins D1 and E was markedly down-regulated in MCs plated on polymerized type I collagen for eight hours in 5% FCS, as compared with MCs on monomer type I collagen. (biomedsearch.com)
Phosphatidylinositol 3-kina1
- It has been shown that Notch-promoted survival and trophic effects in pre-T cells are mediated by the phosphatidylinositol 3-kinase (PI3K)-Akt pathway ( 6 ). (aacrjournals.org)
Cancers4
- The PI3 kinase inhibitor taselisib in combination with the hormone therapy drug letrozole is under study for the treatment of estrogen receptor-positive, HER2-negative early breast cancers in the neoadjuvant (before surgery) setting [ 57 ]. (komen.org)
- A second G1 drug, G1T38, is in development for cancers that depend on the CDK4/6 enzymes. (xconomy.com)
- A separate Phase 2 trial in patients whose breast cancers are dependent on CDK4/6 is also expected to start next year. (xconomy.com)
- Modelling of Protein Kinase Signaling Pathways in Melanoma and Other Cancers. (wikipathways.org)
Cells12
- Prostate carcinoma cells express high levels of interleukin-6 (IL-6) and IL-6 receptor. (nih.gov)
- In this study, we examined the effect of IL-6 on LNCaP human prostate carcinoma cells. (nih.gov)
- In addition, IL-6-treated LNCaP cells induced neuron-like morphological changes. (nih.gov)
- The p40cdk6 protein was present in resting cells and increased amounts were detected 6 h after stimulation. (jimmunol.org)
- Surprisingly, however, IL-6 stimulated STAT binding to this promoter in both sensitive and resistant cell lines (with one exception), suggesting that gross deregulation of this event is not the unifying cause of the defect in p21WAF1/CIP1 induction in IL-6 resistant cells. (nih.gov)
- Kinase requirements in human cells: II. (aacrjournals.org)
- Cyclin-dependent kinase 11 (CDK11) is crucial in the growth of liposarcoma cells. (nih.gov)
- In contrast to mammalian cells, these yeast cells had only one CDK which interacted with various cyclins. (news-medical.net)
- If the tight control over the CDK-cyclin system breaks down, then cells can proliferate uncontrollably. (news-medical.net)
- This is particularly surprising because in contrast to the intractable quiescence of adult human β-cells, fetal and neonatal human β-cells can and do replicate transiently from ~5 months antepartum to ~6 months postpartum ( 13 - 15 ). (diabetesjournals.org)
- This effect is markedly enhanced in cells with a compromised p53-p21-dependent post-mitotic checkpoint. (dana-farber.org)
- G1 wants trilaciclib to block CDK4/6 in these healthy cells, which would pause their division. (xconomy.com)
Tumors1
- Human melanoma cell lines derived from early stage primary tumors are particularly sensitive to growth arrest induced by interleukin-6 (IL-6). (nih.gov)
Human5
- Taken together, these findings establish a role for APE1 as a master regulator of TLR2-dependent inflammatory responses in human keratinocytes. (jimmunol.org)
- "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C" . Proceedings of the National Academy of Sciences of the United States of America . (wikipedia.org)
- RT "A family of human cdc2-related protein kinases. (genome.jp)
- Generating homozygous and hemizygous WT human TDP-43 transgenic mouse lines, we show here a dose-dependent degeneration of cortical and spinal motor neurons and development of spastic quadriplegia reminiscent of ALS. (pnas.org)
- 5 ]]. With around 10-20,000 Mb [ 6 ], conifer genomes are more than 100 times larger than that of Arabidopsis and three times larger than the human genome. (biomedcentral.com)
Enzyme4
- PI3 kinase is an enzyme important in cell growth. (komen.org)
- They provide all the optimized components (enzyme, preferred substrate, required cofactors, buffer) that you need to generate a kinase selectivity profile for a compound. (promega.com)
- Below each tab is a list of currently available Kinase Enzyme Systems (or those coming soon). (promega.com)
- Click on any enzyme for additional information (such as Applications Note, the Catalog Page, or the NCBI Database entry) for that kinase. (promega.com)
Binds1
- Finally, cyclin B binds to CDK-1 to drive the cycle forward into M phase, stimulating mitosis. (news-medical.net)
Targeting1
- Benson C, Kaye S, Workman P, Garrett M, Walton M, de Bono J. Clinical anticancer drug development: targeting the cyclin-dependent kinases. (springer.com)
Ibrance1
- Ibrance is a cyclin-dependent kinase 4/6 inhibitor. (breastcancer.org)