• Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. (wikipedia.org)
  • CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. (wikipedia.org)
  • CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. (wikipedia.org)
  • The structure of human Cdk2 revealed that CDKs have a modified ATP-binding site that can be regulated by cyclin binding. (wikipedia.org)
  • Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (nature.com)
  • Among the major cyclin-dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG-SW3 cells, and its expression is down-regulated during differentiation into osteocytes. (lu.se)
  • Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. (escholarship.org)
  • A relatively well understood example is the network that controls progression of the cell cycle, where cyclin-dependent kinases (CDKs) couple with various cyclins over the cell cycle to regulate critical processes [ 2 - 4 ]. (biomedcentral.com)
  • Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). (biomedcentral.com)
  • CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
  • The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). (biomedcentral.com)
  • Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
  • D-type and E-type cyclins assemble with CDKs during the G1 phase and these holoenzymes act as rate-limiting controllers to regulate passage through the restriction point and the subsequent onset of DNA replication [ 2 , 3 ]. (biomedcentral.com)
  • Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
  • Furthermore, CDK-activating kinase (CAK) phosphorylates cyclin-bound CDKs on a single threonine residue, a modification that is essential for their activity [ 6 - 9 ]. (biomedcentral.com)
  • Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
  • The eukaryotic cell cycle comprises a series of events, whose ordering and correct progression depends on the oscillating activity of cyclin-dependent kinases (Cdks), which safeguard timely duplication and segregation of the genome. (unimi.it)
  • OBJECTIVE: To review preclinical and clinical information on flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent. (usuhs.edu)
  • Increasing numbers of sequence and biochemical data show the involvement of cyclin-dependent kinases (CDKs) and cyclins in regulation of the cell cycle progression in higher plants. (bibbase.org)
  • The complexity represented by different types of CDKs and cyclins in a single species such as alfalfa, indicates that multicomponent regulatory pathways control G2/M transition. (bibbase.org)
  • Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. (nature.com)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. (escholarship.org)
  • A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
  • 2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. (guidetopharmacology.org)
  • We studied the roles of cyclin-dependent kinase inhibitors Cdkn2a and Cdkn2b, known as cellular stress-related senescence markers, in N-methyl-d-aspartate (NMDA)-induced RGC death. (elsevierpure.com)
  • Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
  • We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. (nih.gov)
  • [ 2 ] Options for second-line therapy in patients with relapsed/refractory disease include chemotherapy-free regimens with biologic targeted agents such as covalent Bruton tyrosine kinase (BTK) inhibitors, lenalidomide,venetoclax, and chimeric antigen receptor (CAR) T-cell therapy. (medscape.com)
  • Palbociclib and ribociclib are cyclin-dependent kinases (CDK) 4, 6 inhibitors indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. (medscape.com)
  • Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (jefferson.edu)
  • Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
  • Protein kinases are ubiquitous components of cellular signalling networks [ 1 ]. (biomedcentral.com)
  • Of these, indirubin-3'-monoxime, SP 600125, KT 5823 and ML-9 were found to inhibit a number of protein kinases and conclusions drawn from their use in cell-based assays are likely to be erroneous. (nih.gov)
  • Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. (nih.gov)
  • The protein encoded by this gene is a neuron-specific activator of CDK5 kinase. (nih.gov)
  • It associates with CDK5 to form an active kinase. (nih.gov)
  • This protein and neuron-specific CDK5 activator CDK5R1/p39NCK5A both share limited similarity to cyclins, and thus may define a distinct family of cyclin-dependent kinase activating proteins. (nih.gov)
  • Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that has been implicated in learning, synaptic plasticity, neurotransmission, and numerous neurological disorders. (elsevierpure.com)
  • Inhibitor-1, the first identified endogenous inhibitor of protein phosphatase 1 (PP-1), was previously reported to be a substrate for cyclin-dependent kinase 5 (Cdk5) at Ser 67 . (elsevierpure.com)
  • Thus, inhibitor-1 serves as a critical junction between kinase- and phosphatase-signaling pathways, linking PP-1 to not only PKA and calcineurin but also Cdk5. (elsevierpure.com)
  • In this study, we examined the expression and subcellular localization of cyclin-dependent kinase 5 (Cdk5), cyclin D1, and cyclin E in Leydig and Sertoli cell lines that were cultured with 7.5, 1.0, 0.5, or 0% serum (mixture of a 2:1 ratio of horse serum and fetal bovine serum) and in the developing rat testis to verify the possible functions of Cdk5, cyclin D1, and cyclin E in the testis. (elsevierpure.com)
  • The abundance of Cdk5 and cyclin E in the Leydig cell line, TM3, was significantly reduced at low serum concentrations. (elsevierpure.com)
  • In contrast, serum concentration had no effect on Cdk5 and cyclin E levels in the Sertoli cell line, TM4. (elsevierpure.com)
  • The kinase activity of Cdk5 in TM3 and TM4 cells that were cultured at various serum concentrations coincided with the levels of Cdk5 expression. (elsevierpure.com)
  • Immunohistochemical staining for Cdk5 and cyclin E revealed nuclear and cytoplasmic distribution, both in TM3 and TM4 cells. (elsevierpure.com)
  • Immunohistochemical localization of Cdk5, cyclin D1, and cyclin E in 1-week- old and adult rat testes revealed expression in both Leydig and Sertoli cells. (elsevierpure.com)
  • Ashok B. Kulkarni, Ph.D., has spent years studying a protein called cyclin-dependent kinase 5 (Cdk5). (medlineplus.gov)
  • Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)
  • Activation of cyclin-dependent kinases requires association of the enzyme with a regulatory subunit referred to as a cyclin. (expasy.org)
  • It is the sequential activation and inactivation of cyclin-dependent kinases, through the periodic synthesis and destruction of cyclins, that provides the primary means of cell-cycle regulation. (expasy.org)
  • Cyclin-Dependent Kinases" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (jefferson.edu)
  • Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. (jefferson.edu)
  • This graph shows the total number of publications written about "Cyclin-Dependent Kinases" by people in this website by year, and whether "Cyclin-Dependent Kinases" was a major or minor topic of these publications. (jefferson.edu)
  • Below are the most recent publications written about "Cyclin-Dependent Kinases" by people in Profiles. (jefferson.edu)
  • Regulation of the DNA damage response by cyclin-dependent kinases / C. Trovesi, N. Manfrini, M. Falcettoni, M.P. Longhese. (unimi.it)
  • The Cdc25A dual-specificity phosphatase promotes cell cycle progression by dephosphorylating and activating the cyclin-dependent kinases. (pitt.edu)
  • Brasier, AR 2008, ' Expanding role of cyclin dependent kinases in cytokine inducible gene expression ', Cell Cycle , vol. 7, no. 17, pp. 2661-2666. (utmb.edu)
  • only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. (wikipedia.org)
  • Substrate specificity of S cyclins is imparted by the hydrophobic batch (centered on the MRAIL sequence), which has affinity for substrate proteins that contain a hydrophobic RXL (or Cy) motif. (wikipedia.org)
  • 1992, 1993) that the p34cdc2/cyclin B complex associates with microtubules in the mitotic spindle and premeiotic aster in starfish oocytes, and that microtubule-associated proteins (MAPs) might be responsible for this interaction. (rupress.org)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
  • Reversible phosphorylation of proteins by kinases and phosphatases plays a key regulatory role in several eukaryotic cellular functions including the control of the division cycle. (bibbase.org)
  • article{meszaros_multiple_2000, title = {Multiple cyclin-dependent kinase complexes and phosphatases control {G2}/{M} progression in alfalfa cells}, volume = {43}, issn = {1573-5028}, url = {https://doi.org/10.1023/A:1006412413671}, doi = {10/cb64mn}, abstract = {Reversible phosphorylation of proteins by kinases and phosphatases plays a key regulatory role in several eukaryotic cellular functions including the control of the division cycle. (bibbase.org)
  • The model is based on a bicyclic phosphorylation-dephosphorylation cascade involving cyclin and cdc2 kinase. (ebi.ac.uk)
  • Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)
  • Cyclin-CDK complexes phosphorylate substrates appropriate for the particular cell cycle phase. (wikipedia.org)
  • Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. (wikipedia.org)
  • Here we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5 and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28) substrates. (nature.com)
  • Although we did not identify any highly Clb2-specific substrates, we found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1, enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets. (nature.com)
  • Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. (escholarship.org)
  • The Positive Transcriptional Elongation Factor b (P-TEFb), a heterodimer of CDK9 and Cyclin T1, is widely implicated in control of basal gene expression. (utmb.edu)
  • In mammalian cells, CDK1, with its partners cyclin A2 and B1, alone can drive the cell cycle. (wikipedia.org)
  • Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region. (wikipedia.org)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • DHA-enriched fish oil upregulates cyclin-dependent kinase inhibitor 2A (P16 INK ) expression and downregulates telomerase activity without modulating effects of PPARγ Pro12Ala polymorphism in type 2 diabetic patients: A randomized, double-blind, placebo-controlled clinical trial. (bvsalud.org)
  • The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. (nih.gov)
  • This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D1, Cdk4, INK4a and INK4b, pRb etc. (nih.gov)
  • Methods: Colony-forming assay and apoptotic rates were evaluated to compare the sensitivity of different colon carcinoma cell lines to ionizing radiation and their radiosensitivity upon exposure to BRAF and/or cyclin-dependent kinase 1 inhibitory/silencing strategies. (unifg.it)
  • Most of the known cyclin-CDK complexes regulate the progression through the cell cycle. (wikipedia.org)
  • Cyclin-CDK complexes of earlier cell-cycle phase help activate cyclin-CDK complexes in later phase. (wikipedia.org)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
  • Lundberg, A. S. & Weinberg, R. A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. (nature.com)
  • CDK2+Cyclin A1 NanoBRET Target Engagement Intracellular Kinase Assay for screening of compounds binding to the target. (reactionbiology.com)
  • HEK293 cells transiently expressing NanoLuc-CDK2 + Cyclin A1 Fusion Vector were seeded into the wells of 384-well plates. (reactionbiology.com)
  • and 3) to explore the mechanism by which Cdk2 kinase activity regulates Cdc25A protein turnover. (pitt.edu)
  • The results of our studies revealed that Cdc25A protein half-life in non-stressed interphase cells is regulated, in part, by Cdk2 kinase activity, and that Cdk2 does not regulate Cdc25A turnover by affecting several known signal transduction pathways that control Cdc25A protein stability. (pitt.edu)
  • The kinase(s) responsible for phosphorylating these serine residues remain to be identified, although Cdk2 could be one prime candidate. (pitt.edu)
  • There is considerable specificity in which cyclin binds with CDK. (wikipedia.org)
  • Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
  • One of the kinases that place the tyrosine phosphate is Wee1, a kinase conserved in all eukaryotes. (wikipedia.org)
  • We conclude that the vac5-1 allele directs the Pho85 kinase to regulate, via transcription factors Pho4 and Pho2, genes that affect vacuole inheritance but which are not known to be under normal PHO pathway control. (rupress.org)
  • To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin-dependent kinase complex Bur1/2 as a regulator of telomere length. (johnshopkins.edu)
  • Cyclin D1 regulates cellular migration through the inhibition of thrombospondin 1 and ROCK signaling. (jefferson.edu)
  • The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. (johnshopkins.edu)
  • By constructing stability diagrams showing domains of periodic behavior as a function of the maximum rates of the kinases and phosphatases involved in the two cycles of the cascade, we investigate the role of these converter enzymes in the oscillatory mechanism. (ebi.ac.uk)
  • PHO80 encodes a cyclin which acts in a complex with a cdc-like kinase, PHO85, as a negative regulator of two transcription factors (PHO2 and PHO4) that govern the expression of metabolic phosphatases. (rupress.org)
  • Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. (rupress.org)
  • The vacuole inheritance defect in vac5-1 cells is dependent on the presence of the Pho85 kinase and its targets Pho4p and Pho2p. (rupress.org)
  • Kinases are a major pharmaceutical target, and FBDD has been successfully applied to several of these targets. (ox.ac.uk)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
  • Interaction between alfalfa mitotic cyclin (Medsa;CycB2;1) and a kinase partner has been reported previously. (bibbase.org)
  • Localization of Cdc2Ms F kinase to the preprophase band (PPB), the perinuclear ring in early prophase, the mitotic spindle and the phragmoplast indicated a pivotal role for this kinase in mitotic plant cells. (bibbase.org)
  • Another one, CDK7, is involved indirectly as the CDK-activating kinase. (wikipedia.org)
  • In yeast cells, it occurs before cyclin binding. (wikipedia.org)
  • The present yeast two-hybrid analyses showed differential interaction between defined D-type cyclins and Cdc2Ms kinases functioning in G2/M phases. (bibbase.org)
  • By definition, a CDK binds a regulatory protein called a cyclin. (wikipedia.org)
  • Assignment of CDK5R2 coding for the cyclin-dependent kinase 5, regulatory subunit 2 (NCK5AI protein) to human chromosome band 2q35 by fluorescent in situ hybridization. (nih.gov)
  • An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. (childrensmercy.org)
  • Finally, we examine co-clustering of the CDK consensus motifs with the 'cy' or RXL motif [ 17 ], which is known to be important in determining which CDK-cyclin complex will phosphorylate a given substrate. (biomedcentral.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in Tissue homogenates and other biological fluids. (hudsen.org)
  • Description: A sandwich quantitative ELISA assay kit for detection of Human Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in samples from tissue homogenates or other biological fluids. (jemsec.com)
  • We investigated protein levels of the signaling pathway: p35, cyclin-dependent kinase 5, Munc18a, syntaxin 1A and 1B, Munc18-interacting protein 1 and Munc18-interacting protein 2 in Alzheimer's disease cortex and found that this pathway was up-regulated in the Alzheimer's disease parietal and occipital cortex. (eur.nl)
  • Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation. (johnshopkins.edu)
  • Consistently, cyclin-dependent kinase 1 inhibition/silencing as well as its targeting, through inhibition of HSP90 quality control pathway, significantly inhibited the clonogenic ability and increased apoptotic rates in HT29 cells upon exposure to radiation. (unifg.it)
  • G?ller M, Toualbi-Abed K, Legrand A, Michel L, Mauviel A, Bernuau D, Daniel F. c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1. (jefferson.edu)
  • Cyclins can directly bind the substrate or localize the CDK to a subcellular area where the substrate is found. (wikipedia.org)
  • Cyclin-dependent kinase 1 expression/subcellular distribution was studied by immunoblot analysis. (unifg.it)
  • cyclin L CDK levels remain relatively constant throughout the cell cycle and most regulation is post-translational. (wikipedia.org)
  • CAK activity is not regulated by known cell-cycle pathways and cyclin binding is the limiting step for CDK activation. (wikipedia.org)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • Schindler K, Benjamin KR, Martin A, Boglioli A, Herskowitz I, Winter E. The Cdk-activating kinase Cak1p promotes meiotic S phase through Ime2p. (jefferson.edu)
  • In this study, we have investigated the mechanism by which p34cdc2 kinase associates with the microtubule cytoskeleton in primate tissue culture cells whose major MAP is known to be MAP4. (rupress.org)
  • Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. (jefferson.edu)
  • The molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). (medscape.com)
  • These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. (johnshopkins.edu)
  • In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. (usuhs.edu)
  • Cyclin-dependent kinase 5 and its activator p35 disrupt Munc18a-syntaxin 1 binding, thereby promoting synaptic vesicle fusion during exocytosis. (eur.nl)
  • A truncated form of the Pho80 cyclin redirects the Pho85 kinase to disrupt vacuole inheritance in S. cerevisiae. (rupress.org)
  • Localization to the chromocenters is mediated by an N-terminal domain, in addition we find that this domain may be involved in cyclin binding. (uni-bielefeld.de)