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Cyclin D1Cyclin ACyclin ECyclin BCyclin B1Cyclin D2Cyclin D3Cyclin A1Cyclin A2Cyclin DCyclin G1Cyclin GCyclinsCyclin CCyclin-Dependent KinasesCyclin B2Cyclin TCyclin-Dependent Kinase 2Cyclin G2Cyclin HCell CycleCyclin-Dependent Kinase 4CDC2-CDC28 KinasesCDC2 Protein KinaseG1 PhaseCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p27S PhaseRetinoblastoma ProteinCyclin IMitosisOncogene ProteinsGenes, bcl-1Protein-Serine-Threonine KinasesCyclin-Dependent Kinase 6PhosphorylationCyclin-Dependent Kinase Inhibitor p21Cell DivisionG2 PhaseCell ProliferationTumor Suppressor ProteinsCell Line, TumorRNA, MessengerE2F Transcription Factorscdc25 PhosphatasesMolecular Sequence DataProto-Oncogene ProteinsCell NucleusTumor Cells, CulturedMicrotubule-Associated ProteinsGene Expression Regulation, NeoplasticProliferating Cell Nuclear AntigenF-Box ProteinsProtamine KinaseG0 PhaseCell LineProtein BindingBlotting, WesternMaturation-Promoting FactorDown-RegulationImmunohistochemistryTranscription FactorsTransfectionPromoter Regions, GeneticCyclin-Dependent Kinase Inhibitor p16Nuclear ProteinsGene Expression RegulationTranscription Factor DP1ApoptosisCyclin-Dependent Kinase 9HeLa CellsStarfishSignal Transduction3T3 CellsRetinoblastoma-Binding Protein 1Tumor Suppressor Protein p53Transcription, GeneticE2F1 Transcription FactorDNA-Binding ProteinsRetinoblastoma-Like Protein p107Amino Acid SequenceBase SequenceCells, CulturedProtein KinasesUbiquitin-Protein Ligase ComplexesMutationRecombinant Fusion ProteinsCDC28 Protein Kinase, S cerevisiaeS-Phase Kinase-Associated ProteinsEnzyme ActivationCyclin-Dependent Kinase Inhibitor ProteinsRNA, Small InterferingBreast NeoplasmsEnzyme InhibitorsOocytesLymphoma, Mantle-CellKi-67 AntigenNIH 3T3 CellsFibroblastsReverse Transcriptase Polymerase Chain Reaction
KinasesCDKsProteinsCytoplasmPhosphorylationRole in transcriptional regulationTranscriptional regulationMitotic cyclinSubunitsDependentDegradationSubstrateInhibitorSpecificityCdk1Cdk4BindsGeneCdc2InteractionMitosisSerineYeastDistinctInhibitionExpressionReplicationImmunogenCDK9GenesEnzymesAntibodyMoleculeCompoundsPolymeraseCell cycle reguSpeciesSequenceActivityHumanTissueTransition
Kinases17
CDKs7
  • The structure of CDKs in complex with a cyclin subunits (CDKC) has long been a goal of structural and cellular biologists starting in the 1990s when the structure of unbound cyclin A was solved by Brown et al. (wikipedia.org)
  • These cyclin binding sites are the regions of highest variability in CDKs despite relatively high sequence homology surrounding the αL-12 Helix motif of this structural component. (wikipedia.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)
  • Cyclins contain a conserved amino acid sequence motif, the cyclin box, which allows their binding to cdks to form active complexes that regulate progression of the cell cycle. (bdbiosciences.com)
  • Thus, levels of the four different cyclins vary in predictable patterns and combine with consistent CDKs at specific points to achieve forward momentum. (jove.com)
  • The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
Proteins5
  • We tested interactions between Drosophila cyclins and a panel of hundreds of previously identified proteins. (fhcrc.org)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)
  • Cyclins are a group of proteins that play a key role in the control and regulation of the cell cycle. (iiarjournals.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)
Cytoplasm1
  • Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of Drosophila Male Meiosis. (nih.gov)
Phosphorylation9
  • It is at this essential residue (T160 in CDK2 complexes, T177 in CDK6 complexes) that enzymatic ATP-phosphorylation of CDK-cyclin complexes by CAK (cyclin activating kinase, referring to the CDK7-Cyclin H complex in human cells) takes place. (wikipedia.org)
  • After the hydrolysis of ATP to phosphorylate at this site, these complexes are able to complete their intended function, the phosphorylation of cellular targets. (wikipedia.org)
  • Study of this residue has shown that phosphorylation promotes a conformational change that prevents ATP and substrate binding by steric interference with these necessary binding sites in the activation loop of the CDK-cyclin complexes. (wikipedia.org)
  • Thus, this hinge region, which can vary in length slightly between CDK type and CDK-cyclin complex, connects essential regulatory regions of the CDK by connecting these lobes, and plays key roles in the resulting structure of CDK-cyclin complexes by properly orienting ATP for easy catalysis of phosphorylation reactions by the assembled complex. (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)
  • Phosphorylation assays also revealed that at least three kinase complexes (Cdc2Ms A/B, D and F) were successively active in G2/M cells after synchronization. (bibbase.org)
  • however tyrosine phosphorylation was indicated in the case of Cdc2Ms A kinase and the p13suc1-bound kinase activity was increased by treatment of this complex with recombinant Drosophila Cdc25. (bibbase.org)
  • Moreover, our data show an increase in glycogen synthase kinase-3beta activity, which triggers phosphorylation-dependent cyclin D1 degradation. (unife.it)
  • The various markers that enable assessment of the progression of preneoplastic lesions to spindle cell carcinoma include the p16 protein, which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). (bvsalud.org)
Role in transcriptional regulation1
  • The enzyme is activated by its interaction with CYCLIN C and plays a role in transcriptional regulation by phosphorylating RNA POLYMERASE II. (bvsalud.org)
Transcriptional regulation2
  • Open form structures correspond most often to those complexes involved in transcriptional regulation (CDK 8, 9, 12, and 13), while closed form CDK-cyclin complex are most often involved in cell cycle progression and regulation (CDK 1, 2, 6). (wikipedia.org)
  • Group 3 cyclins (G1, G2 and I) may play a role distinct from either cell cycle or transcriptional regulation. (bdbiosciences.com)
Mitotic cyclin3
  • 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)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • Interaction between alfalfa mitotic cyclin (Medsa;CycB2;1) and a kinase partner has been reported previously. (bibbase.org)
Subunits1
  • Mitotic cyclins stably associate with CDC2 and function as regulatory subunits. (caslab.com)
Dependent20
  • A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic subunit of a protein kinase, cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin. (wikipedia.org)
  • Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. (rcsb.org)
  • Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. (rcsb.org)
  • Our approach thus provides insight into structure, functions, and biochemistry of a cyclin-dependent kinase. (rcsb.org)
  • Enables cyclin-dependent protein serine/threonine kinase regulator activity. (nih.gov)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Schulman, B. A., Lindstrom, D. L. & Harlow, E. Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. (nature.com)
  • Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. (fhcrc.org)
  • Because Cdi4 was originally identified by its ability to interact with a Drosophila cyclin-dependent kinase, the finding that it interacts with cyclin E strengthened the notion that it functions in cell cycle regulation. (fhcrc.org)
  • S-phase kinase-associated protein 2 (SKP2) is an important cell cycle regulator, targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is frequently overexpressed in breast cancer. (umass.edu)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • Concurrent deletion of cyclin E1 and cyclin-dependent kinase 2 in hepatocytes inhibits DNA replication and liver regeneration in mice. (nature.com)
  • Cell cycle-dependent cytotoxicity, G2/M phase arrest, and disruption of p34cdc2/cyclin B1 activity induced by doxorubicin in synchronized P388 cells. (aspetjournals.org)
  • Our results suggest that anthracycline-induced cytotoxicity is cell cycle dependent and is mediated, at least in part, by disturbance of the regulation of p34cdc2/cyclin B1 complex, thus leading to G2/M phase arrest. (aspetjournals.org)
  • cyclin-dependent kinase 5, regulatory. (wikigenes.org)
  • CDK9 (cyclin-dependent kinase 9) is a member of the cyclin-dependent protein kinase family. (thermofisher.com)
  • CDK9 is a member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex. (thermofisher.com)
  • A CYCLIN C dependent kinase that is an important component of the mediator complex. (bvsalud.org)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
Degradation5
  • Cyclin A degradation employs preferentially used lysines and a cyclin box function other than Cdk1 binding. (nih.gov)
  • Cyclin F, encoded by CCNF, is the substrate recognition component of the Skp1-Cul1-F-box E3 ubiquitin ligase complex, SCF cyclin F . E3 ubiquitin ligases play a key role in ubiquitin-proteasome mediated protein degradation, an essential component of protein homeostatic mechanisms within the cell. (edu.au)
  • Moreover, treatment with both SRIH and BIM-23120 decreases cyclin D1 levels, with a parallel increase in phosphocyclin D1 levels, suggesting protein degradation. (unife.it)
  • In contrast, Dox treatment was found to induced cyclin B1 accumulation as a result of stimulating its synthesis and inhibiting its degradation. (aspetjournals.org)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (genetex.com)
Substrate4
  • Substrate specificity of the activated complex is mainly established by the associated cyclin within the complex. (wikipedia.org)
  • This activity is aided by the notable flexibility that the Gly-rich loop has within the structure of most CDK allowing for its rotation toward the activation loop to have a significant effect on reducing substrate affinity without major changes in the overall CDK-cyclin complex structure. (wikipedia.org)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • A cyclin E-CDK2 substrate called NPAT has been found to be associated with histone gene clusters, and cyclin E-CDK2 bolsters activation of histone gene transcription by NPAT. (news-medical.net)
Inhibitor2
  • The work represents the first successful iterative synthesis of a potent CDK inhibitor based on the structure of fully activated CDK2-cyclin A. Furthermore, the potency of O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine was both predicted and fully rationalized on the basis of protein-ligand interactions. (rcsb.org)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
Specificity2
  • Tissue specificity of cyclin B expression in D. melanogaster]. (nih.gov)
  • Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
Cdk12
  • Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (bdbiosciences.com)
  • We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB ). (biologists.com)
Cdk42
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (genetex.com)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
Binds2
  • For instance, during G1, when one type of cyclin, named D, is synthesized and binds to a CDK, the cell transitions into S phase, as another cyclin, E, peaks and forms a complex with CDK to promote DNA replication. (jove.com)
  • p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding. (mpg.de)
Gene7
  • The identity of the higher molecular weight band (~ 45 kD) has not been determined, but may represent an alternative splice product of the cyclin C gene. (bdbiosciences.com)
  • The identity of this protein has not been determined, but may represent an alternative splice product of the cyclin C gene, as has been identified in other species. (bdbiosciences.com)
  • Cyclin C may play a dual role within the cell in its ability to regulate both cell cycle progression as well as gene transcription. (bdbiosciences.com)
  • Background/Aim: Cyclin D1 gene (CCND1) has a G to A polymorphism at the splice donor site of exon 4, position 870. (iiarjournals.org)
  • Cyclin D1, a 45-kDa protein encoded by the cyclin D1 gene ( CCND1 ) on 11q13, is one such molecule. (iiarjournals.org)
  • In this study, we examined the interplay between genes encoding components of the PAF1 complex and VPS36, the gene located next to CDC73 on chromosome XII. (thebiogrid.org)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (genetex.com)
Cdc22
  • Because Cdc2 kinase is important for cell entry into mitosis, cyclin C's ability to regulate cell cycle progression may be attributed, in part, to modulation of Cdc2 protein expression.6 Cyclin C has a predicted molecular weight of 36 kD. (bdbiosciences.com)
  • CDC2 is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF) , which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. (caslab.com)
Interaction2
  • One of the connections we identified was the interaction between cyclin E and a novel Drosophila protein, Cdi4. (fhcrc.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)
Mitosis1
  • After A is degraded, concentrations of cyclin B peak in M phase and the complex will activate the different stages of mitosis. (jove.com)
Serine1
  • In CDK-cyclin complexes, this activation region is composed of a conserved αL-12 Helix and contains a key phosphorylatable residue (usually Threonine for CDK-cyclin partners, but also includes Serine and Tyrosine) that mediates the enzymatic activity of the CDK. (wikipedia.org)
Yeast2
  • We show that Cdi4 can inhibit cyclin E function both in a yeast assay and in vitro. (fhcrc.org)
  • Cis and trans interactions between genes encoding PAF1 complex and ESCRT machinery components in yeast. (thebiogrid.org)
Distinct1
  • 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)
Inhibition1
  • Oncostatin M induces growth arrest by inhibition of Skp2, Cks1, and cyclin A expression and induced p21 expression. (mpg.de)
Expression5
  • Cyclin A expression above the median predicted an improved patient prognosis (HR = 0.71, 95%CI: 0.53 - 0.95). (ox.ac.uk)
  • CONCLUSION: This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer. (ox.ac.uk)
  • Like many cyclins, the expression of cyclin C oscillates throughout the cell cycle, with a peak observed during G1 phase. (bdbiosciences.com)
  • Expression of cyclin D1 has been reported to be a strong predictor for the clinical outcome of OSCC ( 4 ), and amplification of CCND1 was found significantly more frequently in patients with OSCC than in healthy controls ( 5 ), suggesting the predictive and prognostic value of this molecule and its potential as a therapeutic target. (iiarjournals.org)
  • Total RNA from tumors the expression of thousands of genes (3) to address complex questions was isolated using two successive rounds of Trizol. (lu.se)
Replication2
  • By recognising and regulating the availability of several protein substrates, SCF cyclin F plays a role in regulating various cellular processes including replication and repair of DNA and cell cycle checkpoint control. (edu.au)
  • Cyclin E-CDK2 is also needed for the DNA replication and centrosome duplication events in S phase. (news-medical.net)
Immunogen1
  • The polyclonal antiserum reacts with human and mouse cyclin C. A polypeptide fragment containing amino acids 290-303 (QGPNGSQNSSYSQS) at the C-terminus of human cyclin C, with the addition of a C-terminal cysteine (C) residue to facilitate conjugation to KLH, was used as immunogen. (bdbiosciences.com)
CDK91
  • The CDK9/cyclin-K complex also has kinase activity towards CTD of RNAPII and can substitute for CDK9/cyclin-T P-TEFb in vitro. (thermofisher.com)
Genes1
Enzymes1
  • E is then degraded by cytoplasmic enzymes and cyclin A concentrations increase throughout the S phase and remain high into G2 to promote entry into the M phase when in an active complex. (jove.com)
Antibody3
Molecule1
  • Another central challenge is identifying the molecule or molecules driving biological activity in a complex mixture from nature. (eurekalert.org)
Compounds1
  • and discover new compounds (parkamycins A and B) with complex biological activity. (eurekalert.org)
Polymerase2
  • This complex facilitates the transition from abortive to productive elongation by phosphorylating the CTD of the large subunit of RNA polymerase II, POLR2A, SUPT5H, and RDBP. (thermofisher.com)
  • It is a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II. (caslab.com)
Cell cycle regu1
Species1
Sequence1
  • It is important to note that in CDK 1, 2 and 6, the T-loop and a separate C-terminal region are the major sites of cyclin binding in the CDK, and which cyclins are bound to each of these CDK is mediated by the particular sequence of the activation site T-loop. (wikipedia.org)
Activity4
  • p27 regulates G1 /S transition by abrogating the activity of cyclin/CDK complexes. (umass.edu)
  • To this end, transgenic plants with cyclin promoter-GFP fusions will be infected and in vivo GFP activity followed. (europa.eu)
  • The A allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. (iiarjournals.org)
  • This truncated variant, cyclin D1b, does not have the part which is required for export from the nucleus into other cell localizations and therefore has higher transforming activity ( 8 ). (iiarjournals.org)
Human2
Tissue1
  • Mismatch repair, minichromosome maintenance complex component 2, cyclin A, and transforming growth factor β receptor type II as prognostic factors for colorectal cancer: results of a 10-year prospective study using tissue microarray analysis. (ox.ac.uk)
Transition2
  • Cyclins can be categorized as G 1 , G 1 /S, S, or M cyclins based on the cell cycle phase or transition they are most involved in. (jove.com)
  • We then studied the effect of Dox on the p34cdc2/cyclin B1 complex because it plays a key role in regulating G2/M phase transition. (aspetjournals.org)