Cyclin dependent kinase 5. Medical search

Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.

A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.

Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.

A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.

A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.

A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.

Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.

A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.

A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.

The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.

A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.

A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.

Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.

A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.

A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.

A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.

A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.

The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.

A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.

A group of cell cycle proteins that negatively regulate the activity of CYCLIN/CYCLIN-DEPENDENT KINASE complexes. They inhibit CELL CYCLE progression and help control CELL PROLIFERATION following GENOTOXIC STRESS as well as during CELL DIFFERENTIATION.

A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.

A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.

A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.

Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.

Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.

Agents that inhibit PROTEIN KINASES.

A cyclin D subtype which is regulated by GATA4 TRANSCRIPTION FACTOR. Experiments using KNOCKOUT MICE suggest a role for cyclin D2 in granulosa cell proliferation and gonadal development.

A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.

High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.

A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.

Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.

An E2F transcription factor that interacts directly with RETINOBLASTOMA PROTEIN and CYCLIN A and activates GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F1 is involved in DNA REPAIR and APOPTOSIS.

A widely-expressed cyclin A subtype that functions during the G1/S and G2/M transitions of the CELL CYCLE.

Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.

A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 5; cyclin G associated kinase, and PROTEIN PHOSPHATASE 2.

A cell line derived from cultured tumor cells.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.

A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.

A cyclin G subtype that is constitutively expressed throughout the cell cycle. Cyclin G1 is considered a major transcriptional target of TUMOR SUPPRESSOR PROTEIN P53 and is highly induced in response to DNA damage.

An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.

A transcription factor that possesses DNA-binding and E2F-binding domains but lacks a transcriptional activation domain. It is a binding partner for E2F TRANSCRIPTION FACTORS and enhances the DNA binding and transactivation function of the DP-E2F complex.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.

A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Established cell cultures that have the potential to propagate indefinitely.

Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.

Transport proteins that carry specific substances in the blood or across cell membranes.

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.

Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.

A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.

A cyclin B subtype that colocalizes with GOLGI APPARATUS during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.

A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.

A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.

A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.

A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.

A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.

Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.

A cyclin subtype that is found as a component of a heterotrimeric complex containing cyclin-dependent kinase 7 and CDK-activating kinase assembly factor. The complex plays a role in cellular proliferation by phosphorylating several CYCLIN DEPENDENT KINASES at specific regulatory threonine sites.

An unusual cyclin subtype that is found highly expressed in terminally differentiated cells. Unlike conventional cyclins increased expression of cyclin G2 is believed to cause a withdrawal of cells from the CELL CYCLE.

The rate dynamics in chemical or physical systems.

A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.

A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.

Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.

A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.

A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.

A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.

Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.

A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).

An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

Elements of limited time intervals, contributing to particular results or situations.

A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.

A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.

A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.

ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.

A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.

Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.

A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.

A group of phenyl benzopyrans named for having structures like FLAVONES.

Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.

A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.

A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.

An E2F transcription factor that represses GENETIC TRANSCRIPTION required for CELL CYCLE entry and DNA synthesis. E2F4 recruits chromatin remodeling factors indirectly to target gene PROMOTER REGIONS through RETINOBLASTOMA LIKE PROTEIN P130 and RETINOBLASTOMA LIKE PROTEIN P107.

Proteins prepared by recombinant DNA technology.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.

A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.

A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.

A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.

The process by which a DNA molecule is duplicated.

The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.

Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.

A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.

A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.

A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.

Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).

Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.

Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.

Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.

A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.

Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.

A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.

The relationship between the dose of an administered drug and the response of the organism to the drug.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.

Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.

A ubiquitously expressed regulatory protein that contains a retinoblastoma protein binding domain and an AT-rich interactive domain. The protein may play a role in recruiting HISTONE DEACETYLASES to the site of RETINOBLASTOMA PROTEIN-containing transcriptional repressor complexes.

A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.

Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.

A family of non-receptor, PROLINE-rich protein-tyrosine kinases.

A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.

A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.

The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.

An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.

A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

Derivatives of the steroid androstane having two double bonds at any site in any of the rings.

A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.

The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.

A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

The B-cell leukemia/lymphoma-1 genes, associated with various neoplasms when overexpressed. Overexpression results from the t(11;14) translocation, which is characteristic of mantle zone-derived B-cell lymphomas. The human c-bcl-1 gene is located at 11q13 on the long arm of chromosome 11.

Tumors or cancer of the human BREAST.

PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.

A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.

The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.

A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes

A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)

Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.

A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.

A casein kinase that was originally described as a monomeric enzyme with a molecular weight of 30-40 kDa. Several ISOENZYMES of casein kinase I have been found which are encoded by separate genes. Many of the casein kinase I isoenzymes have been shown to play distinctive roles in intracellular SIGNAL TRANSDUCTION.

Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.

A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.

A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.

Neuronal differentiation and patterning in Xenopus: the role of cdk5 and a novel activator xp35.2. (1/634)

Cdk5, a member of the cyclin-dependent kinase family, has been shown to play an important role in development of the central nervous system in mammals when partnered by its activator p35. Here we describe the cloning and characterization of a novel activator of cdk5 in Xenopus, Xp35.2. Xp35.2 is expressed during development initially in the earliest differentiating primary neurons in the neural plate and then later in differentiating neural tissue of the brain. This is in contrast to the previously described Xenopus cdk5 activator Xp35.1 which is expressed over the entire expanse of the neural plate in both proliferating and differentiating cells. Expression of both Xp35.1 and Xp35.2 and activation of cdk5 kinase occur when terminal neural differentiation is induced by neurogenin and neuro D overexpression but not when only early stages of neural differentiation are induced by noggin. Moreover, blocking cdk5 kinase activity specifically results in disruption and reduction of the embryonic eye where cdk5 and its Xp35 activators are expressed. Thus, cdk5/p35 complexes function in aspects of neural differentiation and patterning in the early embryo and particularly in formation of the eye. (+info)

Identification and structure characterization of a Cdk inhibitory peptide derived from neuronal-specific Cdk5 activator. (2/634)

The activation of cyclin-dependent kinase 5 (Cdk5) depends on the binding of its neuronal specific activator Nck5a. The minimal activation domain of Nck5a is located in the region of amino acid residues 150 to 291 (Tang, D., Chun, A. C. S., Zhang, M., and Wang, J. H. (1997) J. Biol. Chem. 272, 12318-12327). In this work we show that a 29-residue peptide, denoted as the alphaN peptide, encompassing amino acid residues Gln145 to Asp173 of Nck5a is capable of binding Cdk5 to result in kinase inhibition. This peptide also inhibits an active phospho-Cdk2-cyclin A complex, with a similar potency. Direct competition experiments have shown that this inhibitory peptide does not compete with Nck5a or cyclin A for Cdk5 or Cdk2, respectively. Steady state kinetic analysis has indicated that the alphaN peptide acts as a non-competitive inhibitor of Cdk5. Nck5a complex with respect to the peptide substrate. To understand the molecular basis of kinase inhibition by the peptide, we determined the structure of the peptide in solution by circular dichroism and two-dimensional 1H NMR spectroscopy. The peptide adopts an amphipathic alpha-helical structure from residues Ser149 to Arg162 which can be further stabilized by the helix-stabilizing solvent trifluoroethanol. The hydrophobic face of the helix is likely to be the kinase binding surface. (+info)

Identification of substrate binding site of cyclin-dependent kinase 5. (3/634)

Cyclin-dependent kinase 5 (CDK5), unlike other CDKs, is active only in neuronal cells where its neuron-specific activator p35 is present. However, it phosphorylates serines/threonines in S/TPXK/R-type motifs like other CDKs. The tail portion of neurofilament-H contains more than 50 KSP repeats, and CDK5 has been shown to phosphorylate S/T specifically only in KS/TPXK motifs, indicating highly specific interactions in substrate recognition. CDKs have been shown to have a high preference for a basic residue (lysine or arginine) as the n+3 residue, n being the location in the primary sequence of a phosphoacceptor serine or threonine. Because of the lack of a crystal structure of a CDK-substrate complex, the structural basis for this specific interaction is unknown. We have used site-directed mutagenesis ("charged to alanine") and molecular modeling techniques to probe the recognition interactions for substrate peptide (PKTPKKAKKL) derived from histone H1 docked in the active site of CDK5. The experimental data and computer simulations suggest that Asp86 and Asp91 are key residues that interact with the lysines at positions n+2 and/or n+3 of the substrates. (+info)

DNA binding protein dbpA binds Cdk5 and inhibits its activity. (4/634)

Progress in the cell cycle is governed by the activity of cyclin dependent kinases (Cdks). Unlike other Cdks, the Cdk5 catalytic subunit is found mostly in differentiated neurons. Interestingly, the only known protein that activates Cdk5 (i.e. p35) is expressed solely in the brain. It has been suggested that, besides its requirement in neuronal differentiation, Cdk5 activity is induced during myogenesis. However, it is not clear how this activity is regulated in the pathway that leads proliferative cells to differentiation. In order to find if there exists any Cdk5-interacting protein, the yeast two-hybrid system was used to screen a HeLa cDNA library. We have determined that a C-terminal 172 amino acid domain of the DNA binding protein, dbpA, binds to Cdk5. Biochemical analyses reveal that this fragment (dbpA(Cdelta)) strongly inhibits p35-activated Cdk5 kinase. The protein also interacts with Cdk4 and inhibits the Cdk4/cyclin D1 enzyme. Surprisingly, dbpA(Cdelta) does not bind Cdk2 in the two-hybrid assay nor does it inhibit Cdk2 activated by cyclin A. It could be that dbpA's ability to inhibit Cdk5 and Cdk4 reflects an apparent cross-talk between distinct signal transduction pathways controlled by dbpA on the one hand and Cdk5 or Cdk4 on the other. (+info)

Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous. (5/634)

Cyclin-dependent kinase 5 (Cdk5) is a member of the family of cell cycle-related kinases. Previous neuropathological analysis of cdk5(-/-) mice showed significant changes in CNS development in regions from cerebral cortex to brainstem. Among the defects in these animals, a disruption of the normal pattern of cell migrations in cerebellum was particularly apparent, including a pronounced abnormality in the location of cerebellar Purkinje cells. Complete analysis of this brain region is hampered in the mutant because most of cerebellar morphogenesis occurs after birth and the cdk5(-/-) mice die in the perinatal period. To overcome this disadvantage, we have generated chimeric mice by injection of cdk5(-/-) embryonic stem cells into host blastocysts. Analysis of the cerebellum from the resulting cdk5(-/-) left arrow over right arrow cdk5(+/+) chimeric mice shows that the abnormal location of the mutant Purkinje cells is a cell-autonomous defect. In addition, significant numbers of granule cells remain located in the molecular layer, suggesting a failure to complete migration from the external to the internal granule cell layer. In contrast to the Purkinje and granule cell populations, all three of the deep cerebellar nuclear cell groupings form correctly and are composed of cells of both mutant and wild-type genotypes. Despite similarities of the cdk5(-/-) phenotype to that reported in reeler and mdab-1(-/-) (scrambler/yotari) mutant brains, reelin and disabled-1 mRNA were found to be normal in cdk5(-/-) brain. Together, the data further support the hypothesis that Cdk5 activity is required for specific components of neuronal migration that are differentially required by different neuronal cell types and by even a single neuronal cell type at different developmental stages. (+info)

Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation. (6/634)

Cyclin-dependent kinase 5 (cdk5) is found in an active form only in neuronal cells. Activation by virtue of association with the cyclin-like neuronal proteins p35 (or its truncated form p25) and p39 is the only mechanism currently shown to regulate cdk5 catalytic activity. In addition to cyclin binding, other members of the cdk family require for maximal activation phosphorylation of a Ser/Thr residue (Thr(160) in the case of cdk-2) that is conserved in all cdks except cdk8. This site is phosphorylated by cdk-activating kinases, which, however, do not phosphorylate cdk5. To examine the possible existence of a phosphorylation-dependent regulatory mechanism in the case of cdk5, we have metabolically labeled PC12 cells with (32)P(i) and shown that the endogenous cdk5 is phosphorylated. Bacterially expressed cdk5 also can be phosphorylated by PC12 cell lysates. Phosphorylation of cdk5 by a PC12 cell lysate results in a significant increase in cdk5/p25 catalytic activity. Ser(159) in cdk5 is homologous to the regulatory Thr(160) in cdk2. A Ser(159)-to-Ala (S159A) cdk5 mutant did not show similar activation, which suggests that cdk5 is also regulated by phosphorylation at this site. Like other members of the cdk family, cdk5 catalytic activity is influenced by both p25 binding and phosphorylation. We show that the cdk5-activating kinase (cdk5AK) is distinct from the cdk-activating kinase (cyclin H/cdk7) that was reported previously to neither phosphorylate cdk5 nor affect its activity. We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro. (+info)

Inhibition of tau phosphorylating protein kinase cdk5 prevents beta-amyloid-induced neuronal death. (7/634)

The key target of this study was the tau protein kinase II system (TPK II) involving the catalytic subunit cdk5 and the regulatory component p35. TPK II is one of the tau phosphorylating systems in neuronal cells, thus regulating its functions in the cytoskeletal dynamics and the extension of neuronal processes. This research led to demonstration that the treatment of rat hippocampal cells in culture with fibrillary beta-amyloid (Abeta) results in a significant increase of the cdk5 enzymatic activity. Interestingly, the data also showed that the neurotoxic effect of 1-20 microM Abeta on primary cultures markedly diminished with co-incubation of hippocampal cells with the amyloid fibers plus the cdk5 inhibitor butyrolactone I. This inhibitor protected brain cells against Abeta-induced cell death in a concentration dependent fashion. Moreover, death was also prevented by a cdk5 antisense probe, but not by an oligonucleotide with a random sequence. The cdk5 antisense also reduced neuronal expression of cdk5 compared with the random oligonucleotide. The studies indicate that cdk5 plays a major role in the molecular path leading to the neurodegenerative process triggered by the amyloid fibers in primary cultures of rat hippocampal neurons. These findings are of interest in the context of the pathogenesis of Alzheimer's disease. (+info)

Neuron-specific Cdk5 kinase is responsible for mitosis-independent phosphorylation of c-Src at Ser75 in human Y79 retinoblastoma cells. (8/634)

c-Src is phosphorylated at specific serine and threonine residues during mitosis in fibroblastic and epithelial cells. These sites are phosphorylated in vitro by the mitotic kinase Cdk1 (p34(cdc2)). In contrast, c-Src in Y79 human retinoblastoma cells, which are of neuronal origin, is phosphorylated at one of the mitotic sites, Ser75, throughout the cell cycle. The identity of the serine kinase that nonmitotically phosphorylates c-Src on Ser75 remains unknown. We now are able to show for the first time that Cdk5 kinase, which has the same consensus sequence as the Cdk1 and Cdk2 kinases, is required for the phosphorylation in asynchronous Y79 cells. The Ser75 phosphorylation was inhibited in a dose-dependent manner by butyrolactone I, a specific inhibitor of Cdk5-type kinases. Three stable subclones that have almost no kinase activity were selected by transfection of an antisense Cdk5-specific activator p35 construct into Y79 cells. The loss of the kinase activity caused an approximately 85% inhibition of the Ser75 phosphorylation. These results present compelling evidence that Cdk5/p35 kinase is responsible for the novel phosphorylation of c-Src at Ser75 in neuronal cells, raising the intriguing possibility that c-Src acts as an effector of Cdk5/p35 kinase during neuronal development. (+info)

There are different types of Breast Neoplasms such as:

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

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

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

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

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

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

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

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

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

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

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

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

See also: Cancer, Tumor

Word count: 190

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

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

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

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

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

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

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

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

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

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

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

Types of Neoplasms

There are many different types of neoplasms, including:

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

Causes and Risk Factors of Neoplasms

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

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

Signs and Symptoms of Neoplasms

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

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

Diagnosis and Treatment of Neoplasms

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

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

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

Prevention of Neoplasms

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

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

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

There are several types of lung neoplasms, including:

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

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

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

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

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

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

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

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

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

There are several types of colonic neoplasms, including:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

... membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". The Journal of Neuroscience. 23 (12): ... The molecule belongs to the cyclin-dependent kinase family. Kinases are enzymes that catalyze reactions of phosphorylation. ... Cyclin-dependent kinase 5 is a protein, and more specifically an enzyme, that is encoded by the Cdk5 gene. It was discovered 15 ... Cyclin Dependent Kinase 5. Springer. 19 August 2008. ISBN 978-0-387-78886-9. Patrick GN, Zukerberg L, Nikolic M, de la Monte S ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_5

This gene provides instructions for making a protein (cyclin-dependent kinase-like 5) that is essential for normal brain ... Olson, Heather E. (2019). Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder: clinical review (PDF). CDKL5 Alliance ... or Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder". ClinicalTrials.gov. Retrieved 21 June 2021. Devinsky, Orrin ( ... "Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review". Pediatric Neurology. 97: 18-25. doi:10.1016/j. ...

https://en.wikipedia.org/wiki/CDKL5_deficiency_disorder

Cyclin-dependent kinase 5 (Cdk5), a major regulator of neuronal migration and positioning, is known to phosphorylate DAB1 and ... Ohshima T, Suzuki H, Morimura T, Ogawa M, Mikoshiba K (April 2007). "Modulation of Reelin signaling by Cyclin-dependent kinase ... Keshvara L, Magdaleno S, Benhayon D, Curran T (June 2002). "Cyclin-dependent kinase 5 phosphorylates disabled 1 independently ... "Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the positioning of cortical neurons in the ...

https://en.wikipedia.org/wiki/Reelin

... 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 CDKL5 deficiency disorder GRCh38: Ensembl release 89: ... The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of ...

https://en.wikipedia.org/wiki/CDKL5

Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene. The protein encoded by this ... "Entrez Gene: CDK5R2 cyclin-dependent kinase 5, regulatory subunit 2 (p39)". Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai ... Patzke H, Tsai LH (March 2002). "Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29". The Journal ... Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH (September 2002). "The cyclin-dependent kinase 5 activators p35 and p39 ...

https://en.wikipedia.org/wiki/CDK5R2

Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene. The protein encoded by this ... "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)". Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). " ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH (September 2002). "The cyclin-dependent kinase 5 activators p35 and p39 ...

https://en.wikipedia.org/wiki/CDK5R1

Lee SY, Wenk MR, Kim Y, Nairn AC, De Camilli P (January 2004). "Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at ... 10 (5): 703-713. doi:10.1101/gr.10.5.703. PMC 310876. PMID 10810093. Modregger J, Schmidt AA, Ritter B, Huttner WB, Plomann M ( ... 4 (5): 345-349. doi:10.1093/dnares/4.5.345. PMID 9455484. Howard L, Nelson KK, Maciewicz RA, Blobel CP (October 1999). " ... "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1-2): 149-156. doi: ...

https://en.wikipedia.org/wiki/SH3GLB1

"Distinct roles for cyclin-dependent kinases in cell cycle control." Science 262.5142 (1993): 2050-2054. Harlow, E. D., et al. " ... "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5." (1994): 419-423. Meyerson, Matthew, et al. "A family ... Tsai, L (1994). "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature. 371: 419-23. doi:10.1038/ ... van den Heuvel, S (1993). "Distinct roles for cyclin-dependent kinases in cell cycle control". Science. 262: 2050-4. doi: ...

https://en.wikipedia.org/wiki/Ed_Harlow

"Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18". The Journal of Biological Chemistry. 274 ... Wierda KD, Toonen RF, de Wit H, Brussaard AB, Verhage M (April 2007). "Interdependence of PKC-dependent and PKC-independent ... March 1996). "Phosphorylation of Munc-18/n-Sec1/rbSec1 by protein kinase C: its implication in regulating the interaction of ... This protein is essential for presynpatic vesicle release and is rapidly phosphorylated by protein kinase C upon neuronal ...

https://en.wikipedia.org/wiki/STXBP1

In the Harlow laboratory, Tsai studied cyclin-dependent kinases in order to identify their role in cell division. Tsai became ... "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature. 371 (6496): 419-423. Bibcode:1994Natur.371.. ... "Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system". Development. 119 (4): 1029 ... Nikolic, M.; Dudek, H.; Kwon, Y. T.; Ramos, Y. F.; Tsai, L. H. (1996-04-01). "The cdk5/p35 kinase is essential for neurite ...

https://en.wikipedia.org/wiki/Li-Huei_Tsai

... has been shown to interact with Cyclin-dependent kinase 5. GRCh38: Ensembl release 89: ENSG00000132688 - ... "Mitotic reorganization of the intermediate filament protein nestin involves phosphorylation by cdc2 kinase". Journal of ... 5 (12): 3310-28. doi:10.1523/JNEUROSCI.05-12-03310.1985. PMC 6565218. PMID 4078630. Lothian C, Lendahl U (1997). "An ...

https://en.wikipedia.org/wiki/Nestin_(protein)

Sustained D1 receptor activity is kept in check by Cyclin-dependent kinase 5. Dopamine receptor activation of Ca2+/calmodulin- ... dependent protein kinase II can be cAMP dependent or independent. The cAMP mediated pathway results in amplification of PKA ... Beta arrestin has been shown to form complexes with MAP kinase, leading to activation of extracellular signal-regulated kinases ... Dopamine receptors can also transactivate Receptor tyrosine kinases. Beta Arrestin recruitment is mediated by G-protein kinases ...

https://en.wikipedia.org/wiki/Dopamine_receptor

CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... cyclin A, cyclin B CDK2; cyclin A, cyclin E CDK3; cyclin C CDK4; cyclin D1, cyclin D2, cyclin D3 CDK5; CDK5R1, CDK5R2. See also ... A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase

"Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5". Journal of ... "In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3beta". Journal ... 16 (5): 609-19. doi:10.1006/mcne.2000.0884. PMID 11083922. S2CID 54379424. Hussain I, Christie G, Schneider K, Moore S, ...

https://en.wikipedia.org/wiki/Beta-secretase_2

July 2007). "Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation". Nature ... Calcium/calmodulin-dependent protein kinases Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (March 1997). "Molecular ... Reelin modulates NMDA function through Src family kinases and DAB1. significantly enhancing LTP in the hippocampus. Src kinase ... "MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term ...

https://en.wikipedia.org/wiki/NMDA_receptor

... to study the protein ligand interaction in cyclin-dependent kinase 5 and even to show the effect of electric field on thrombin ... "Steered molecular dynamics simulations for studying protein-ligand interaction in cyclin-dependent kinase 5". Journal of ... beta-secretase 1 and check point kinase 1 as case studies". Journal of Computer-aided Molecular Design. 30 (12): 1149-1163. ... 331 (5-6): 446-454. Bibcode:2000CPL...331..446B. doi:10.1016/S0009-2614(00)01215-X. Lemkul JA, Bevan DR (February 2010). " ...

https://en.wikipedia.org/wiki/Molecular_dynamics

"Entrez Gene: CDK10 cyclin-dependent kinase (CDC2-like) 10". Kasten M, Giordano A (Apr 2001). "Cdk10, a Cdc2-related kinase, ... Cyclin-dependent kinase 10 has been shown to interact with ETS2. GRCh38: Ensembl release 89: ENSG00000185324 - Ensembl, May ... This kinase has been shown to play a role in cellular proliferation. Its function is limited to cell cycle G2-M phase. At least ... Cell division protein kinase 10 is an enzyme that in humans is encoded by the CDK10 gene. The protein encoded by this gene ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_10

Cyclin D1, Cyclin D3, P16, PPM1B, and PPP2CA. Cell cycle Cyclin-dependent kinase Cyclin-dependent kinase 4 Mitosis The ... 2003). "Expression of Cyclin-Dependent Kinase 6, but Not Cyclin-Dependent Kinase 4, Alters Morphology of Cultured Mouse ... "Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. The protein ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_6

... has been shown to interact with: BRCA1, CDK2AP1, CDKN1B CDKN3, CEBPA, Cyclin A1, Cyclin E1, Flap ... CDK2 cyclin-dependent kinase 2". Echalier A, Endicott JA, Noble ME (March 2010). "Recent developments in cyclin-dependent ... Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ... The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_2

"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... Cyclin-dependent kinase 7, or cell division protein kinase 7, is an enzyme that in humans is encoded by the CDK7 gene. The ... Cyclin-dependent kinase 7 has been shown to interact with: Androgen receptor, Cyclin H, GTF2H1, MNAT1, P53, SUPT5H, and XPB. ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)". Patel H, Abduljabbar R, Lai ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_7

... or CDK9 is a cyclin-dependent kinase associated with P-TEFb. The protein encoded by this gene is a ... Cyclin-Dependent+Kinase+9 at the US National Library of Medicine Medical Subject Headings (MeSH) Drosophila Cyclin dependent ... "Entrez Gene: CDK9 cyclin-dependent kinase 9 (CDC2-related kinase)". MacLachlan TK, Sang N, De Luca A, Puri PL, Levrero M, ... Singh R, Bhardwaj VK, Das P, Purohit R (November 2019). "Natural analogues inhibiting selective cyclin-dependent kinase protein ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_9

"Entrez Gene: CDK3 cyclin-dependent kinase 3". Bullrich F, MacLachlan TK, Sang N, et al. (1995). "Chromosomal mapping of members ... 2002). "ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3)". Eur. J. Biochem. 268 (23): 6076-82. doi:10.1046/j. ... Meikrantz W, Schlegel R (1996). "Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases". J ... Ren S, Rollins BJ (2004). "Cyclin C/cdk3 promotes Rb-dependent G0 exit". Cell. 117 (2): 239-51. doi:10.1016/S0092-8674(04)00300 ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_3

"Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8". Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ... Cyclin-dependent kinase 8 has been shown to interact with: CCNC CREB binding protein CRSP3 MED1 MED12 MED14 MED16 MED17 MED21 ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_8

"Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings". The Journal of Biological ... Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels ... Li C, Ullrich B, Zhang JZ, Anderson RG, Brose N, Südhof TC (June 1995). "Ca(2+)-dependent and -independent activities of neural ... Beckman ML, Bernstein EM, Quick MW (August 1998). "Protein kinase C regulates the interaction between a GABA transporter and ...

https://en.wikipedia.org/wiki/STX1A

These include the Aristaless related homeobox (ARX) and cyclin dependent kinase like 5 (CDKL5) genes. The ARX gene in ... Statistically, 5 out of every 100 children with West syndrome do not survive beyond five years of age, in some cases due to the ... West syndrome appears in 1% to 5% of infants with Down syndrome. This form of epilepsy is relatively difficult to treat in ... Mol Syndromol 2(3-5):137-152 Sherr EH (2003) The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): ...

https://en.wikipedia.org/wiki/Epileptic_spasms

... has been shown to interact with Cyclin-dependent kinase 5, YWHAE, PAFAH1B1 and DISC1. GRCh38: Ensembl release 89: ... Phosphorylation regulates the cell cycle-dependent distribution of this protein, with a fraction of the protein bound strongly ... 44 (5): 809-21. doi:10.1016/j.neuron.2004.11.019. PMID 15572112. Hayashi MA, Portaro FC, Bastos MF, Guerreiro JR, Oliveira V, ... ATF4/5 and NUDEL: regulation and loss of interaction with mutation". Human Molecular Genetics. 12 (13): 1591-608. doi:10.1093/ ...

https://en.wikipedia.org/wiki/NDEL1

"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ... 5 (1): 48-55. doi:10.1016/0959-440x(95)80008-o. PMID 7773747. Schimmel P, Giegé R, Moras D, Yokoyama S (October 1993). "An ... 42 (5): 1703-13. doi:10.1007/s00726-011-0872-8. PMID 21400228. S2CID 2996097. Prokaryotic AARS database: Chaliotis, et al. (Feb ...

https://en.wikipedia.org/wiki/Aminoacyl_tRNA_synthetase

January 2007). "Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor ... "Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase ... Phosphorylation of TRPV1 by protein kinase C have been shown to play a role in sensitization of TRPV1. The cleavage of PIP2 by ... Premkumar LS, Ahern GP (December 2000). "Induction of vanilloid receptor channel activity by protein kinase C". Nature. 408 ( ...

https://en.wikipedia.org/wiki/TRPV1

In eukaryotes, cyclin-dependent protein kinases interact with cyclins to regulate cell cycle progression, and are required for ... the cyclin-dependent kinase regulatory subunit family is a family of proteins consisting of the regulatory subunits of cyclin- ... Six kinase units can be modelled to bind the hexameric structure, which may thus act as a hub for cyclin-dependent protein ... The proteins bind to a regulatory subunit, cyclin-dependent kinase regulatory subunit (CKS), which is essential for their ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_regulatory_subunit_family

... cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin. Once cyclin-dependent kinases bind to cyclin, the formed ... Cyclin Cyclin-dependent kinase Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci. 2005 Nov;30(11 ... Yu DS, Zhao R, Hsu EL, Cayer J, Ye F, Guo Y, Shyr Y, Cortez D. Cyclin-dependent kinase 9-cyclin K functions in the replication ... A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_complex

Zhu D, Dix DJ, Eddy EM (August 1997). "HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes". ... as CDC2 in unable to form the required heterodimer with cyclin B1 for the meiotic cell cycle to progress beyond S phase. ... and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells". The Journal of Biological Chemistry. 287 (23): 19599 ... where it is necessary for the formation of the complex between CDC2 and cyclin B1. It later becomes incorporated into the ...

https://en.wikipedia.org/wiki/HSPA1B

... 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 ...

https://en.wikipedia.org/wiki/MiR-137

Two key classes of regulatory molecules, cyclins and cyclin-dependent kinases (CDKs), determine a cell's progress through the ... cyclin A, DNA polymerase, thymidine kinase, etc. Cyclin E thus produced binds to CDK2, forming the cyclin E-CDK2 complex, which ... Nigg EA (June 1995). "Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle". BioEssays. 17 (6): 471-80 ... October 2003). "Targets of the cyclin-dependent kinase Cdk1". Nature. 425 (6960): 859-64. Bibcode:2003Natur.425..859U. doi: ...

https://en.wikipedia.org/wiki/Cell_cycle

... but their genetic information cannot be organized and separated into chromosomes due to inhibition of cyclin-dependent kinase ... 5 (1): 48-55. doi:10.1016/S0955-0674(05)80007-9. PMID 8448030. Storti RV, Rich A (July 1976). "Chick cytoplasmic actin and ...

https://en.wikipedia.org/wiki/Anthony_Mahowald

15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby ... DP2 and DP1 are G protein-coupled receptors, with the DP2 receptor coupled to Gi alpha subunit-dependent depression of cellular ... Cyclin D1, Cdk4, and Insulin-like growth factor 1; and e) regulating agents such as HSP70, GPR78, Gadd153, Ubiquitin B, and ... It (they) regulates signaling by: a) inhibiting the STAT3-Janus kinase pathway to block cellular pro-inflammatory responses; b ...

https://en.wikipedia.org/wiki/Cyclopentenone_prostaglandins

"The nuclear protein p34SEI-1 regulates the kinase activity of cyclin-dependent kinase 4 in a concentration-dependent manner". ... p21 p53 Cyclin-dependent kinase Cyclin D GRCh38: Ensembl release 89: ENSG00000147889 - Ensembl, May 2017 GRCm38: Ensembl ... "Entrez Gene: CDKN2A cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)". Nobori T, Miura K, Wu DJ, Lois A, ... p16 is an inhibitor of cyclin-dependent kinases (CDK). It slows down the cell cycle by prohibiting progression from G1 phase to ...

https://en.wikipedia.org/wiki/P16

7SK associates with and inhibits the cyclin dependent kinase activity of P-TEFb through the action of the RNA binding proteins ... Yik JH, Chen R, Nishimura R, Jennings JL, Link AJ, Zhou Q (October 2003). "Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA ... Yang Z, Zhu Q, Luo K, Zhou Q (November 2001). "The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control ... July 2003). "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Molecular and ...

https://en.wikipedia.org/wiki/7SK_RNA

"Hsc70 regulates accumulation of cyclin D1 and cyclin D1-dependent protein kinase". Molecular and Cellular Biology. 23 (5): 1764 ... For example, Hsc70 regulates the nuclear accumulation of cyclin D1, which is a key player in G1 to S phase cell cycle ... Hsp70 member proteins, including Hsp72, inhibit apoptosis by acting on the caspase-dependent pathway and against apoptosis- ... 62 (5): 875-87. doi:10.1016/0092-8674(90)90263-E. PMID 1975516. S2CID 9501568. Lim MY, Davis N, Zhang JY, Bose HR (Mar 1990). " ...

https://en.wikipedia.org/wiki/HSPA8

Hennigan RF, Stambrook PJ (August 2001). "Dominant negative c-jun inhibits activation of the cyclin D1 and cyclin E kinase ... AP-1 functions are heavily dependent on the specific Fos and Jun subunits contributing to AP-1 dimers. The outcome of AP-1 ... Navas TA, Baldwin DT, Stewart TA (November 1999). "RIP2 is a Raf1-activated mitogen-activated protein kinase kinase". The ... Manicassamy S, Gupta S, Huang Z, Sun Z (June 2006). "Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up ...

https://en.wikipedia.org/wiki/AP-1_transcription_factor

... cyclin - cyclin A - cyclin B - cyclin E - cyclin-dependent kinase - cycloleucine - cyclosporin - cyclosporine - cystatin - ... ribosomal protein S6 kinase - ribosome - RNA - RNA virus - RNA-binding protein - RNA-directed DNA polymerase - rod outer ... CDC28 protein kinase - cell - cell adhesion molecule - cell biology - cell cycle protein - cell membrane - cell membrane ... kinase - kinesin - kinetic energy - kinetic exclusion assay - kinetics - knock-out mouse - Krebs cycle lactalbumin - lactic ...

https://en.wikipedia.org/wiki/Index_of_biochemistry_articles

... phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other ... Cux transcription factor by cyclin A-Cdk1 modulates its DNA binding activity in G(2)". J. Biol. Chem. 276 (49): 45780-90. doi: ... attachment region upstream of the T cell receptor beta gene enhancer binds Cux/CDP and SATB1 and modulates enhancer-dependent ... phosphoinositide-3-kinase interacting protein 1), resulted in higher activity of the growth promoting enzyme, ...

https://en.wikipedia.org/wiki/CUTL1

Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature. ... the pre-replication complex only occurs during late M phase and early G1 phase of the cell cycle when cyclin-dependent kinase ( ... The singular archaeal ORC protein recognizes the AT-rich tracts and binds DNA in an ATP-dependent fashion. Eukaryotes typically ... "DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1". EMBO Reports. 7 (11): 1134- ...

https://en.wikipedia.org/wiki/Pre-replication_complex

"Calmodulin is essential for cyclin-dependent kinase 4 (Cdk4) activity and nuclear accumulation of cyclin D1-Cdk4 during G1". ... 5 (1): 8. doi:10.1186/1471-2164-5-8. PMC 343271. PMID 14728724. Namciu SJ, Friedman RD, Marsden MD, Sarausad LM, Jasoni CL, ... doi:10.1016/s0925-4439(03)00087-5. PMID 12878323. Parker N, Porter AC (January 2004). "Identification of a novel gene family ...

https://en.wikipedia.org/wiki/IFI27

Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... Simone C, Giordano A (2007). "Abrogation of signal-dependent activation of the cdk9/cyclin T2a complex in human RD ... This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb ... "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 23 (14): 4859-69 ...

https://en.wikipedia.org/wiki/Cyclin_T2

... using cyclins and other proteins. As TFIIB has a similar structure to cyclin A it has been suggested that depleted levels of ... It has been suggested that the general transcription factor TFIIH could act as the kinase for this phosphorylation although ... "New core promoter element in RNA polymerase II-dependent transcription: sequence-specific DNA binding by transcription factor ... This is thought to be due to similarity TFIIB has to cyclin A. In order to undergo replication, viruses often stop host cells ...

https://en.wikipedia.org/wiki/Transcription_factor_II_B

... in which 3 paralogues of subunits of the cyclin-dependent kinase module have evolved by 3 independent gene duplication events ... Xu W, Ji JY (2011). "Dysregulation of CDK8 and Cyclin C in tumorigenesis". J Genet Genomics. 38 (10): 439-52. doi:10.1016/j.jgg ... Mediator can be divided into 4 main parts: The head, middle, tail, and the transiently associated CDK8 kinase module. Mediator ... Clark AD, Oldenbroek M, Boyer TG (2015). "Mediator kinase module and human tumorigenesis". Crit Rev Biochem Mol Biol. 50 (5): ...

https://en.wikipedia.org/wiki/Mediator_(coactivator)

... which is required for the function of metaphase cyclin-dependent kinases (M-Cdks). In essence, Activation of the Anaphase- ... Metaphase ends with the destruction of B cyclin. B cyclin is marked with ubiquitin which flags it for destruction by ... Hickson GR, Echard A, O'Farrell PH (February 2006). "Rho-kinase controls cell shape changes during cytokinesis". Current ... promoting complex (APC) causes the APC to cleave the M-phase cyclin and the inhibitory protein securin which activates the ...

https://en.wikipedia.org/wiki/Anaphase

... a well-studied cyclin-dependent protein kinase. Cdc14 antagonizes Cdk1 by stimulating proteolysis of its cyclin partner (cyclin ... It is possible that Cdc14 acts as a phosphatase on all Clb-Cdk1 targets, acting to reverse the effects of the mitotic cyclins. ... April 1999). "Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT ... Furthermore, Cdc14 dephosphorylates the stoichiometric inhibitor of the mitotic cyclins, Sic1, stabilizing Sic1 protein. Cdc14 ...

https://en.wikipedia.org/wiki/Cdc14

TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a ... c-Jun N-terminal kinase (JNK) is a MAP kinase activated by extracellular stress signals such as gamma-radiation, ultraviolet ... EVI1 does not bind other MAP kinases such as p38 or ERK. Among the many other observed defects, EVI1−/− mouse embryos have been ... Together, these two systems disrupt tyrosine kinase signaling and hematopoietic gene transcription. Despite the extensively ...

https://en.wikipedia.org/wiki/MECOM

... it travels to the nucleus via phosphorylation at the Thr-108 position via the mitogenic cyclin dependent kinase (CDK2).[ ... interacts with kinases including serine/threonine protein kinase (PKR). Further studies will need to be performed to better ... E4orf4 partners mainly with protein phosphatase 2A (PP2A) and Src kinases to induce cell death. Modeling of this protein ... This includes presence of cytoplasmic vacuoles, double-membrane vesicles, and a dose-dependent decrease in ATP levels. Melanoma ...

https://en.wikipedia.org/wiki/Anticancer_gene

SKP2 targets p27Kip-1, an inhibitor of cyclin-dependent kinases (CDKs). CDKs2/4 partner with the cyclins E/D, respectively, ... This is achieved by continuous control of cyclins or CDKs levels through ubiquitination and degradation. When cyclin E is ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. ... Moreover, ubiquitination can also act to turn on/off the kinase activity of a protein. The critical role of phosphorylation is ...

https://en.wikipedia.org/wiki/Ubiquitin

"Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis". Nature. 560 (7717): 192-197. Bibcode:2018Natur.560.. ... 7 (7): 740-5. doi:10.1006/cyto.1995.0088. PMID 8580385. Hailu A, van Baarle D, Knol G, et al. (2005). "T Cell and Cytokine ... 62 (5): 487-495. doi:10.1111/j.1365-3083.2005.01686.x. PMID 16305646. S2CID 25506998. Gasim S, Elhassan A, Khalil E, et al. ( ... 5 (11): S7-S16. doi:10.1038/nrmicro1748. PMID 17938629. S2CID 6963295. Pulvertaft, RJ; Hoyle, GF (1960). "Stages in the life- ...

https://en.wikipedia.org/wiki/Visceral_leishmaniasis

... like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate ... Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that ... De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (June 1993). "Crystal structure of cyclin-dependent kinase 2 ... Overview of all the structural information available in the PDB for UniProt: P06493 (Cyclin-dependent kinase 1) at the PDBe-KB ...

https://en.wikipedia.org/wiki/Cyclin-dependent_kinase_1

"Characterization of a new family of cyclin-dependent kinase activators". The Biochemical Journal. 386 (Pt 2): 349-55. doi: ... 110 (5): 429-38. doi:10.1007/s00439-002-0710-x. PMID 12073013. S2CID 29964959. This article incorporates text from the United ...

https://en.wikipedia.org/wiki/SPDYE1

This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent ... kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs ... Serine/threonine-protein kinase PRP4 homolog is an enzyme that in humans is encoded by the PRPF4B gene. Pre-mRNA splicing ... 2002). "Mammalian PRP4 Kinase Copurifies and Interacts with Components of Both the U5 snRNP and the N-CoR Deacetylase Complexes ...

https://en.wikipedia.org/wiki/PRPF4B

Cyclin D, Cyclin E transcriptional regulators: Myc, E2f1, p130 cyclin-dependent kinase inhibitors (CKIs): p27Kip1, p21, Wee1 ... βTRCP recognizes these substrates after they are phosphorylated by Polo-like kinase 1 or Cyclin B-CDK1. Fbw7, which is the ... Schwob, E (1994-10-21). "The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae". Cell. 79 ... SCF-fbxo4 plays a role in cell cycle control by targeting cyclin D1 for degradation. Cyclin F is an FBP that is associated with ...

https://en.wikipedia.org/wiki/SCF_complex

Accumulation of cyclin B increases the activity of the cyclin dependent kinase Cdk1 human homolog Cdc2 as cells prepare to ... The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at ... Chk1 is an effector protein kinase that maintains mitotic cyclin in an inactive state and is phosphorylated by rad3 between S ... pathways which activate the Chk2 and Chk1 kinases, respectively. These kinases act upstream of Cdc25 and Wee1, the direct ...

https://en.wikipedia.org/wiki/G2-M_DNA_damage_checkpoint

Tyrosine kinases are enzymes that add phosphates to tyrosine residues, and are the opposing enzymes to PTPs. PTPs are known to ... cyclin D1 and c-myc. Expression of ful-length PTPkappa in melanoma cells that normally lack its expression results in reduced ... soluble version of the receptor-like protein tyrosine phosphatase kappa stimulates neurite outgrowth via a Grb2/MEK1-dependent ... "Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases". Genome Biol. 7 (1): R5. doi: ...

https://en.wikipedia.org/wiki/PTPRK

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental encephalopathy caused by pathogenic ... Discovery and characterization of a specific inhibitor of serine-threonine kinase cyclin-dependent kinase-like 5 (CDKL5) ... Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review Heather E Olson 1 , Scott T Demarest 2 , Elia M Pestana- ... Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review Heather E Olson et al. Pediatr Neurol. 2019 Aug. ...

https://pubmed.ncbi.nlm.nih.gov/30928302

cyclin-dependent kinase 5 regulatory subunit p35 [Mus musculus] cyclin-dependent kinase 5 regulatory subunit p35 [Mus musculus] ... Enables several functions, including Hsp90 protein binding activity; cyclin-dependent protein serine/threonine kinase activator ... See the reference protein sequence for cyclin-dependent kinase 5 activator 1 (NP_034001.1). ...

https://www.ncbi.nlm.nih.gov/protein?term=txid10090[orgn]%20AND%20%22strain%20C57BL%2F6+129%2FSvJ%22[All%20Fields]

... ... To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression. ... that involves mitogen-activated protein/extracellular signal-regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 ... Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the ...

https://edrn.nci.nih.gov/data-and-resources/publications/21825040-1935-cyclin-dependent-kinase-5-is-amplified-and-overexpressed-in-pancreatic-cancer-and-activated-by-mutant-k-ras/

Cyclin-dependent kinases are regulators and effectors of oscillations driven by a transcription factor network.. Simmons Kovacs ... and mitotic cyclin-CDK complexes. However, periodic events persist in yeast cells lacking all S phase and mitotic B-cyclin ... Here we examine the individual contributions of a transcription factor network and cyclin-CDKs to the maintenance of cell-cycle ... During embryonic cell cycles, B-cyclin-CDKs function as the core component of an autonomous oscillator. Current models for the ...

https://pesquisa.bvsalud.org/saudepublica/resource/pt/mdl-22306294

Cyclin-dependent kinase 2 (CDK2) is a kinase involved in the regulation of cell cycle, being responsible for triggering DNA ... Cyclin-dependent kinase 2 (CDK2) is a kinase involved in the regulation of cell cycle, being responsible for triggering DNA ... Molecular dynamics simulations reveal the determinants of cyclin-dependent kinase 2 inhibition by 5-nitrosopyrimidine ... Molecular dynamics, well-tempered metadynamics, drug design, cyclin-dependent kinase 2, 5-nitrosopyrimidines ...

https://iris.unito.it/handle/2318/1719770

Access to Cyclin-Dependent Kinase-Like 5 (CDKL5) Mutation Analysis is restricted. Sign up now. ...

https://app.medicaldatabase.com/site/medical-tests/559e27b8-0c65-41e5-8578-4a0ce0769f2d?section=references

Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because ... Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because ... Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because ... Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because ...

https://www.scholars.northwestern.edu/en/publications/non-aggregating-tau-phosphorylation-by-cyclin-dependent-kinase-5-

This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ... This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ... This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ... This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found ...

https://okayama.elsevierpure.com/en/publications/cyclin-dependent-kinase-like-5-binds-and-phosphorylates-dna-methy

Cyclin-Dependent Kinase-Like 5 Deficiency Disorder: Clinical Review. Pediatr Neurol. 2019 Aug;97:18-25. doi: 10.1016/j. ... 2012 Apr;2(3-5):137-152. doi: 10.1159/000331333. Epub 2011 Sep 13. Citation on PubMed or Free article on PubMed Central ... 2012 Feb;46(2):101-5. doi: 10.1016/j.pediatrneurol.2011.11.007. Citation on PubMed ...

https://medlineplus.gov/genetics/condition/cdkl5-deficiency-disorder

Cyclin-dependent kinase 5 (Cdk5), a member of the Cdks family, is identified to play a critical role in the development of CNS ... Cyclin-dependent kinase 5 (Cdk5), a member of the Cdks family, is identified to play a critical role in the development of CNS ... The functional roles of cyclin-dependent kinase 5 in neural development. by Fu Wing Yu THESIS 2002 ... The kinase activity of Cdk5 in muscle was also regulated after nerve denervation and NRG treatment. This study also describes a ...

https://lbezone.hkust.edu.hk/bib/b769378

Cyclin-dependent kinase 5 activity regulates pain signaling. Proc Natl Acad Sci U S A. 2006 Jan 17;103(3): 791-796. ... Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential ... Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5 activity during pain signaling through transcriptional ... Activation of cyclin-dependent 5 mediates orofacial mechanical hyperalgesia. Mol Pain. 2013 Dec 21;9: 66. ...

https://www.nidcr.nih.gov/research/conducted-at-nidcr/investigators/ashok-kulkarni

The Potential Role of Cyclin-Dependent Kinase 5 in Focal Cortical Dysplasia ... The Potential Role of Cyclin-Dependent Kinase 5 in Focal Cortical Dysplasia ...

https://www.ndcn.ox.ac.uk/publications/461704

Cyclin-Dependent Kinase 5 Dysfunction Contributes to Depressive-like Behaviors in Huntingtons Disease by Altering the DARPP-32 ... Conformational state-dependent regulation of GABAA receptor diffusion and subsynaptic domains. Merlaud Z, Marques X, Russeau M ... Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries. Bokobza C, ... First quantitative dosages: Strong correlations between non-5-HT2Rs serotonin receptors on normal human heart valves. Schussler ...

https://ifm-institute.org/publications/cyclin-dependent-kinase-5-dysfunction-contributes-to-depressive-like-behaviors-in-huntingtons-disease-by-altering-the-darpp-32-phosphorylation-status-in-the-nucleus-accumbens/

CDC2 Protein Kinase/antagonists & inhibitors; Chromatography, High Pressure Liquid; Cyclin-Dependent Kinase 5; Cyclin-Dependent ... Extracts of the cultures were screened for inhibition of human cyclin-dependent kinases (CDK)-1 and -5 and glycogen synthase ... Abstract: Indigoids, a class of bis-indoles, represent a promising protein kinase inhibitor scaffold. Oxidation of indole by ... Title: Generation of new protein kinase inhibitors utilizing cytochrome p450 mutant enzymes for indigoid synthesis. ...

https://tools.niehs.nih.gov/portfolio/index.cfm?do=portfolio.publicationDetail&id=610230

Cyclin-dependent kinase 5 (CDK5) and neuronal cell death.. Weishaupt JH; Neusch C; Bähr M. Cell Tissue Res; 2003 Apr; 312(1):1- ... 8. Cyclin-dependent kinase inhibitors: novel anticancer agents.. Mani S; Wang C; Wu K; Francis R; Pestell R. Expert Opin ... 9. Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics.. Fischer PM; Lane DP. Curr Med Chem; 2000 Dec; 7(12): ... 1. Cyclin-dependent kinase inhibitors: cancer killers to neuronal guardians.. Monaco EA; Vallano ML. Curr Med Chem; 2003 Mar; ...

https://pubmedhh.nlm.nih.gov/biomarkers/search.php?id=12570697&mod=related&page=1&outid=&proj=

cyclin-dependent kinase 5. acts_upstream_of_or_within. ISO. MGI:1861809 (MGI:1340775,PMID:10407039). RGD. PMID:10407039. MGI: ... mitogen activated protein kinase kinase 1. involved_in. acts_upstream_of_or_within. IEA. ISO. GO_REF:0000107. MGI:99511 (MGI: ... kinase non-catalytic C-lobe domain containing 1. acts_upstream_of_or_within. ISO. (MGI:3769586,PMID:17984326). RGD. PMID: ... unc-51 like autophagy activating kinase 1. acts_upstream_of_or_within. ISO. (MGI:1351063,PMID:10624947). RGD. PMID:10624947. ...

https://rgd.mcw.edu/rgdweb/ontology/annot.html?acc_id=GO:0021697

Indicated for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2 ... This agent works by binding to voltage-dependent sodium channels and inhibiting the generation of action potentials. Serum ... Topiramate has multiple mechanisms of action, including state-dependent sodium channel ̶ blocking action, enhancement of the ... This agent works by blocking voltage-dependent neuronal sodium channels. The therapeutic concentration range of phenytoin in ...

http://emedicine.medscape.com/article/1184846-medication

Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception. Sci Rep. ... Postoperative elevation in creatine kinase and its impact on renal function in patients undergoing complex partial nephrectomy ... Benjamin J. Harrison1,2,3, Juw Won Park3,4, Cynthia Gomes2,5, Jeffrey C. Petruska2,5,6, Matthew R. Sapio7, Michael J. Iadarola7 ...

https://www.cc.nih.gov/dpm/publications.html

https://clinicalcenter.nih.gov/dpm/publications.html

Cyclin-Dependent Kinases [D12.776.167.200] * CDC2-CDC28 Kinases [D12.776.167.200.067] * CDC2 Protein Kinase [D12.776.167.200. ... Cyclin-Dependent Kinases [D12.776.476.563.646.500] * CDC2-CDC28 Kinases [D12.776.476.563.646.500.500] * CDC2 Protein Kinase [ ... Cyclin-Dependent Kinases [D08.811.913.696.620.682.700.646.500] * CDC2-CDC28 Kinases [D08.811.913.696.620.682.700.646.500.500] * ... CDC28 Protein Kinase, S cerevisiae [D08.811.913.696.620.682.700.646.500.500.375] * Cyclin-Dependent Kinase 5 [D08.811.913.696. ...

https://meshb.nlm.nih.gov/record/ui?ui=D051360

Reversal of Collapsing Glomerulopathy in Mice with the Cyclin-Dependent Kinase Inhibitor CYC202. Gherardi, Dana; DAgati, ... May 2004 - Volume 15 - Issue 5 : Journal of the American Society of Nephrology. ... Journal of the American Society of Nephrology. 15(5):A25-A26, May 2004. ... Journal of the American Society of Nephrology. 15(5):1106-1112, May 2004. ...

https://journals.lww.com/jasn/toc/2004/05000

Zhu, L., Ding, R., Zhang, J., Zhang, J. & Lin, Z. Cyclin-dependent kinase 5 acts as a promising biomarker in clear cell Renal ... The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line ... as well as cyclin-dependent kinase 5 (CDK5) signaling, but inhibition of metabolic pathways, namely Oxidative Phosphorylation, ... A data-dependent top 40 method was used during which up to 40 precursor ions were selected from each full MS scan to be ...

https://www.nature.com/articles/s41467-020-18904-9?error=cookies_not_supported&code=371f2c9c-97c8-4a2c-b48b-4e302df33a1c

CYCLIN-DEPENDENT KINASE 21,2-ETHANEDIOL4-(5-AMINO-4-OXO-4H-PYRAZOL-3-YL)-2-BROMO-4,5,6,7-TETRAHYDRO-3AH-PYRROLO[2,3-C]AZEPIN-8- ... 4-(5-AMINO-4-OXO-4H-PYRAZOL-3-YL)-2-BROMO-4,5,6,7-TETRAHYDRO-3AH-PYRROLO[2,3-C]AZEPIN-8-ONE. ...

https://www.ncbi.nlm.nih.gov/Structure/pdb/1DM2

Significance: Evidence suggests that overexpression or aberrant activity of cyclin-dependent kinase 5 (CDK5) leads to neuronal ... In conclusion, FOXO3-dependent hepatic macrophage apoptosis in response to ethanol serves to promote differentiation of ... FOXO3-Dependent Apoptosis Limits Alcohol-Induced Liver Inflammation by Promoting Infiltrating Macrophage Differentiation ... The study first demonstrated that alcohol-induced death of these cells is dependent on a multifunctional transcription factor, ...

https://www.niaaa.nih.gov/about-niaaa/our-work/advisory-council/directors-reports-council/niaaa-directors-report-institute-19

Cyclin-Dependent Kinases [D08.811.913.696.620.682.700.646.500]. *Cyclin-Dependent Kinase 2 [D08.811.913.696.620.682.700.646. ... Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21. ... "Cyclin-Dependent Kinase 2" by people in Harvard Catalyst Profiles by year, and whether "Cyclin-Dependent Kinase 2" was a major ... Cyclin-Dependent Kinase 2 [D08.811.913.696.620.682.700.200.323]. *Proline-Directed Protein Kinases [D08.811.913.696.620.682. ...

https://connects.catalyst.harvard.edu/Profiles/display/Concept/Cyclin-Dependent%20Kinase%202

Indicated for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged ≥2 yr ... Indicated for seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged ≥2 yr ... 5. This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty ...

https://reference.medscape.com/drug/ztalmy-ganaxolone-4000250

Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. Brion, J.P., Couck, A.M. Am. J. ... alpha-Synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in ... This observation suggests that cdk5 might be a protein kinase involved in the phosphorylation of a molecular component of Lewy ...

https://www.wikigenes.org/e/mesh/e/11150.html

p35, a neuron-specific activator of cyclin-dependent kinase 5 (Cdk5), has been studied as a key element in cortical development ... Gilmore EC, Ohshima T, Goffinet AM, Kulkarni AB, Herrup K (1998) Cyclin-dependent kinase 5-deficient mice demonstrate novel ... Neuronal cyclin-dependent kinase 5 activity is critical for survival. J Neurosci 21: 550-558. ... p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 371: 419-423. ...

https://www.jneurosci.org/content/24/41/9005.full

The Cyclin Dependent Kinase 5 Activator p39 Binds Myosin Essential Light Chain ... CB-5 Gao, Chun Y (NEI) C.Y. Gao, F.Y. Qiao, and P.S. Zelenka ... Cdk5 Dependent Regulation of E-Cadherin Junctions in HCLE Cells ...

https://researchfestival.nih.gov/festival05/sessions/CategoryCB.html

Retinoic acid increases glucocorticoid receptor phosphorylation via cyclin-dependent kinase 5 ea0037gp.17.01 ... Receptor tyrosine kinase expression and their role in the response to target therapy in bronchopulmonary NET ... A reappraisal of second line tests in the differential diagnosis of ACTH-dependent Cushings syndrome: the role of three ... A genome-wide shRNA screen to identify genes regulating ERα signalling and oestrogen-dependent proliferation in breast cancer ...

https://www.endocrine-abstracts.org/ea/0037/abstracts/eposter-presentations/clinical-cases-thyroid-other/ea0037ep1329/eposter/

To evaluate the nature of cyclin-dependent kinase 5 (CDK5) hyperactivity in pancreatic cancer progression. (nih.gov)
Inhibition of CDK5 kinase activity using a CDK5 dominant-negative mutant or the drug roscovitine significantly decreased the migration and invasion of pancreatic cancer cells in vitro. (nih.gov)
Increased CDK5 kinase activity was also observed in immortalized human pancreatic nestin-expressing (HPNE) cells expressing a mutant form of K-Ras (G12D) compared with HPNE cells expressing native K-Ras. (nih.gov)
Inhibition of the signaling cascade downstream of mutant K-Ras (G12D) that involves mitogen-activated protein/extracellular signal-regulated kinase, phosphoinositide 3-kinase, or CDK5 decreased p25 protein levels. (nih.gov)
Cyclin-dependent kinase 5 (Cdk5), a member of the Cdks family, is identified to play a critical role in the development of CNS. (edu.hk)
Many efforts have been put on the understanding of Cdk5 functions, the mechanism in regulating its kinase activity is still not clearly elucidated. (edu.hk)
The kinase activity of Cdk5 in muscle was also regulated after nerve denervation and NRG treatment. (edu.hk)
Increased cyclin-dependent kinase 5 (CDK5) activity has recently emerged as a contributor to cancer progression. (cancer.gov)
Here we show that p35, a critical regulator of cyclin-dependent kinase 5 (CDK5), specifically depletes the precursor form of E-cadherin, but not the mature form, by using a precursor-specific antibody. (corc.ac.cn)

This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. (elsevierpure.com)
The CDKL5 protein is a kinase involved in both regulation in the cytoplasm and the nucleus with many, largely unknown downstream targets. (epilepsygenetics.net)
Approximately one fourth of patients with CDKL5 encephalopathy gain the ability to walk independently by the age of 5 years or use single words. (epilepsygenetics.net)
CDKL5 encephalopathy is due to haploinsufficiency of the CDKL5 gene coding for cyclin-dependent kinase-like 5. (epilepsygenetics.net)

Tumor necrosis factor-alpha regulates cyclin-dependent kinase 5 activity during pain signaling through transcriptional activation of p35. (nih.gov)
5. The Secreted Glycoprotein Reelin Suppresses the Proliferation and Regulates the Distribution of Oligodendrocyte Progenitor Cells in the Embryonic Neocortex. (nih.gov)
D1 receptors stimulate adenylyl cyclase, triggering the production of second messenger, 3',5'-cyclic adenosine monophosphate (cAMP) that regulates protein kinase A (PKA) activity, whereas the D2 receptors have the opposite effect. (brainmatrix.com)

Extracts of the cultures were screened for inhibition of human cyclin-dependent kinases (CDK)-1 and -5 and glycogen synthase kinase-3 (GSK3). (nih.gov)
Zou J, Wang W, Pan YW, Abel GM, Storm DR, Xia Z. Conditional Inhibition of Adult Neurogenesis by Inducible and Targeted Deletion of ERK5 MAP Kinase Is Not Associated with Anxiety/Depression-Like Behaviors. (washington.edu)

Although the N-terminal region of Dnmt1 is known to interact with various proteins, such as methyl-CpG-binding protein 2 (MeCP2), the associations of protein kinases with this region have not been reported. (elsevierpure.com)

We investigated via chromatin immunoprecipitation (ChIP) assay whether or not non-androgen stimuli (β-estradiol and EGF) could lead to AR binding to the known androgen receptor elements (AREs) of several genes: prostate specific antigen (PSA), FK506 binding protein 5 (FKBP5), insulin-like growth factor 1 (IGF-1), cyclin-dependent kinase inhibitor 1A (CDKN1A), and transmembrane protease, serine 2 (TMPRSS2). (thermofisher.com)
In earlier publications, this protein was also called serine/threonine protein kinase 9 (STK9). (epilepsygenetics.net)

Indigoids, a class of bis-indoles, represent a promising protein kinase inhibitor scaffold. (nih.gov)

Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1. (nih.gov)
9. Migration of sympathetic preganglionic neurons in the spinal cord is regulated by Reelin-dependent Dab1 tyrosine phosphorylation and CrkL. (nih.gov)
Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent Kinase 5 affects Chemo-nociception. (nih.gov)

On the basis of their epigenomes, intra-telencephalic cells that project to different cortical targets could be further distinguished, and some layer 5 neurons that project to extra-telencephalic targets (L5 ET) formed separate clusters that aligned with their axonal projections. (salk.edu)

Activation of cyclin-dependent 5 mediates orofacial mechanical hyperalgesia. (nih.gov)
Wang H, Engstrom AK, Xia Z. Cadmium impairs the survival and proliferation of cultured adult subventricular neural stem cells through activation of the JNK and p38 MAP kinases. (washington.edu)
Engstrom A, Wang H, Xia Z. Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases. (washington.edu)
Wang W, Lu S, Li T, Pan YW, Zou J, Abel GM, Xu L, Storm DR, Xia Z. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function. (washington.edu)

There is emerging evidence that deregulation of Erythropoietin-producing hepatocellular (Eph) receptor tyrosine kinases (RTK) signaling contributes to the aberrant synaptic functions associated with neurodegeneration. (biomedcentral.com)

Among the proteins ubiquitous in these pathways, Cyclin D1-CDK complex and p53 were found to be predominantly dysregulated in most cancers. (springerprofessional.de)

This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. (nih.gov)
Cyclin-dependent Kinase 5: Novel role of gene variants identified in ADHD. (cdc.gov)

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. (nih.gov)
Eph/ephrin signaling is required for a wide range of biological processes both during embryogenesis and adult life and involves the Eph receptors which form the largest of the 20 subfamilies of human receptor kinases. (biomedcentral.com)
The rod outer segment (ROS) consists of tightly stacked membranous discs wherein the light-sensitive G-protein coupled receptor, rhodopsin, is embedded in high density [ 5 ]. (biomedcentral.com)
[5] Alternative splicing generates two isoforms of the D2 receptor, D2-short (D2s) and D2-long (D2 L ), respectively, and confers different properties that influence its signaling and pharmacology. (brainmatrix.com)

It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation. (nih.gov)

Thus, learning is associated with differential regional modulation of blood oxygenation level-dependent (BOLD) activity or regional cerebral blood flow (rCBF). (pka-signal.com)

14. Modulation of Reelin signaling by Cyclin-dependent kinase 5. (nih.gov)

Cyclin-dependent kinase 5 is amplified and overexpressed in pancreatic cancer and activated by mutant K-Ras. (nih.gov)

The extracts from cultures incubated with 5-methoxyindole were the most inhibitory. (nih.gov)

7. RELN signaling modulates glioblastoma growth and substrate-dependent migration. (nih.gov)

Taken together, these results reveal the unexpected involvement of CdkS kinase in neuregulin signaling at the neuromuscular synapse. (edu.hk)

Generation of new protein kinase inhibitors utilizing cytochrome p450 mutant enzymes for indigoid synthesis. (nih.gov)

Hypoxia-acidosis-mediated cell death was independent of p53: equivalent apoptosis occurred in cardiac myocytes isolated from wild-type and p53 knockout mice, and hypoxia caused no detectable change in p53 abundance or p53-dependent transcription. (jci.org)

The success of the neurotrophic factor treatment is dependent on a successful injection of protein or viral vector, and the dose is dependent on the size of the lesion. (helsinki.fi)
Treatment of aHSCs with quercetin and gallic acid inhibited cell viability in a dose- and time-dependent manner. (ncl.edu.tw)

In the present study, we found that a 110-kDa protein kinase in mouse brain could bind to the N-terminal domain of Dnmt1. (elsevierpure.com)

This agent works by binding to voltage-dependent sodium channels and inhibiting the generation of action potentials. (medscape.com)

In one study of 109 females and 18 males, 75% of females had attained sitting by 5 years, 25% had attained independent walking, 25% of males had attained independent sitting by 15 months, and only 1 (6%) of the males had attained independent walking. (epilepsygenetics.net)

Anatomy15

Organisms8

Diseases2

Chemicals and Drugs164

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes48

Disciplines and Occupations1

Information Science3

Neuronal differentiation and patterning in Xenopus: the role of cdk5 and a novel activator xp35.2. (1/634)

Identification and structure characterization of a Cdk inhibitory peptide derived from neuronal-specific Cdk5 activator. (2/634)

Identification of substrate binding site of cyclin-dependent kinase 5. (3/634)

DNA binding protein dbpA binds Cdk5 and inhibits its activity. (4/634)

Migration defects of cdk5(-/-) neurons in the developing cerebellum is cell autonomous. (5/634)

Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation. (6/634)

Inhibition of tau phosphorylating protein kinase cdk5 prevents beta-amyloid-induced neuronal death. (7/634)

Neuron-specific Cdk5 kinase is responsible for mitosis-independent phosphorylation of c-Src at Ser75 in human Y79 retinoblastoma cells. (8/634)

Cyclin-Dependent Kinases

Cyclin-Dependent Kinase 2

Cyclin D1

Cyclin A

Cyclin E

Cyclins

Cyclin-Dependent Kinase 4

Cyclin-Dependent Kinase Inhibitor p27

CDC2-CDC28 Kinases

Cell Cycle

Cyclin-Dependent Kinase Inhibitor p21

Cyclin-Dependent Kinase 5

Cell Cycle Proteins

Cyclin B

Cyclin C

Protein-Serine-Threonine Kinases

CDC2 Protein Kinase

Cyclin D

G1 Phase

Cyclin-Dependent Kinase Inhibitor p16

Cyclin-Dependent Kinase Inhibitor Proteins

Cyclin D3

Cyclin B1

Retinoblastoma Protein

Phosphorylation

Cyclin-Dependent Kinase 6

Cyclin-Dependent Kinase Inhibitor p57

Tumor Suppressor Proteins

S Phase

Protein Kinase Inhibitors

Cyclin D2

Cyclin A1

Microtubule-Associated Proteins

Protein Kinases

Cell Proliferation

Purines

Cell Division

Apoptosis

Proto-Oncogene Proteins

E2F1 Transcription Factor

Cyclin A2

Phosphatidylinositol 3-Kinases

Cyclin G

Cell Line, Tumor

Tumor Cells, Cultured

Tumor Suppressor Protein p53

Mitosis

Cyclin G1

MAP Kinase Signaling System

Transcription Factor DP1

Signal Transduction

Cells, Cultured

Blotting, Western

Enzyme Inhibitors

G2 Phase

E2F Transcription Factors

Transfection

Calcium-Calmodulin-Dependent Protein Kinases

Mutation

Proliferating Cell Nuclear Antigen

Molecular Sequence Data

Cell Line

DNA-Binding Proteins

Carrier Proteins

Nuclear Proteins

Base Sequence

RNA, Messenger

Protein Kinase C

Transcription Factors

src-Family Kinases

Immunohistochemistry

Reverse Transcriptase Polymerase Chain Reaction

DNA Damage

Antineoplastic Agents

Amino Acid Sequence

p38 Mitogen-Activated Protein Kinases

Cyclic AMP-Dependent Protein Kinases

Cyclin B2

Mitogen-Activated Protein Kinase 1

Protein Binding