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CDC28 Protein Kinase, S cerevisiaeSaccharomyces cerevisiaeCyclinsProtein Kinase CProtein KinasesSaccharomyces cerevisiae ProteinsCDC2 Protein KinaseCyclic AMP-Dependent Protein KinasesProtein-Serine-Threonine KinasesPhosphorylationCalcium-Calmodulin-Dependent Protein KinasesMolecular Sequence DataMitogen-Activated Protein KinasesProtein Kinase InhibitorsMAP Kinase Signaling SystemFungal Proteinscdc25 PhosphatasesPhosphatidylinositol 3-Kinasesp38 Mitogen-Activated Protein KinasesAmino Acid SequenceEnzyme Activationcdc42 GTP-Binding ProteinCyclin-Dependent KinasesMutationMitogen-Activated Protein Kinase 1Signal TransductionGene Expression Regulation, FungalCell Cycle ProteinsMitogen-Activated Protein Kinase KinasesProtein Kinase C-alphaBase SequenceMitogen-Activated Protein Kinase 3Protein Kinase C-deltaCell CycleCdc20 ProteinsJNK Mitogen-Activated Protein KinasesAMP-Activated Protein KinasesIsoenzymesKineticsCDC2-CDC28 KinasesProtein BindingProtein Kinase C-epsilonProtein Kinase C betaProtein-Tyrosine Kinasessrc-Family KinasesEnzyme InhibitorsSequence Homology, Amino AcidCyclin BMitosisCloning, MolecularTetradecanoylphorbol AcetateCyclic GMP-Dependent Protein KinasesCell LineCyclin D3Cells, CulturedRNA, MessengerCyclic AMPSubstrate SpecificityRecombinant Fusion ProteinsMAP Kinase Kinase KinasesCasein Kinase IIDNA-Binding ProteinsBlotting, WesternRecombinant ProteinsTranscription, Geneticp21-Activated KinasesG1 PhaseCalcium-Calmodulin-Dependent Protein Kinase Type 2Transcription FactorsBinding SitesCell DivisionProto-Oncogene ProteinsTransfectionSerineCyclin APlasmidseIF-2 KinaseIntracellular Signaling Peptides and ProteinsPhosphoproteinsProtein Structure, TertiaryCyclin-Dependent Kinase 2RNA, FungalCarrier ProteinsMAP Kinase Kinase 1Nuclear ProteinsCyclin DCalciumModels, BiologicalProto-Oncogene Proteins c-aktExtracellular Signal-Regulated MAP KinasesCyclin D2Ribosomal Protein S6 KinasesCell NucleusCasein KinasesPhosphoprotein PhosphatasesCyclin-Dependent Kinase 4Gene DeletionPhenotypeSchizosaccharomycesMAP Kinase Kinase 4

SaccharomycesCDKsTriggered by the mitoticFission yeastComplexesMitosisCdc2 kinaseSubunitPhosphorylationMitotic cyclinsClb2SubstrateDegradationCln2TranscriptionalSubunitsInhibitsPromotesDependentClb5Evolutionarily conservedInhibitorsPombeRegulatorProgressionCdc6MutantsNuclearActivityDestructionComplexPhaseActivationCdk4PathwayPairsInteractionConsistsRoberts

Saccharomyces8

• Two observations made on the budding yeast Saccharomyces cerevisiae are inconsistent with this scenario: (i) anaphase occurs in the presence of high levels of kinase in cdc15 mutants and (ii) overproduction of a B-type mitotic cyclin causes arrest not in metaphase as previously reported but in telophase. (ox.ac.uk)
• A time lapse experiment of Saccharomyces cerevisiae expressing GFP-tagged SIC1. (ucsd.edu)
• In most eukaryotes, commitment to cell division occurs in late G1 phase at an event called Start in the yeast Saccharomyces cerevisiae, and called the restriction point in mammalian cells. (uky.edu)
• In Saccharomyces cerevisiae , rapamycin binds to the peptidyl-prolyl isomerase Fpr1 leading to the inhibition of the Target of Rapamycin (TOR) kinase that forms the TOR Complex 1 (Torc1) [4, 5]. (researchsquare.com)
• Hadwiger J, Wittenberg C, Mendenhall M, Reed S (1989) The saccharomyces cerevisiae cks1 gene, a homolog of the schizo-saccharomyces pombe suc1+ gene, encodes a subunit of the cdc28 protein kinase complex. (edu.pl)
• In Saccharomyces cerevisiae , the telomere-associated protein Ndj1 is required for bouquet formation. (biorxiv.org)
• Recently, numerous gene expression and molecular interaction experiments have been reported in Saccharomyces cerevisiae , and these have enabled systematic studies. (biomedcentral.com)
• For example, under low-nitrogen conditions, crosstalk is observed between two signaling pathways in Saccharomyces cerevisiae , the cAMP and MAPK pathways, which are both downstream of the small GTPase Ras. (biomedcentral.com)

CDKs3

• Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (nature.com)
• Cell cycle regulation is largely based on protein phospho-dephosphorylation events, catalyzed by cyclin dependent kinases (Cdks) and phosphatases (PPases), respectively. (encyclopedia.pub)
• These changes are orchestrated by a small number of master regulators, including the cyclin-dependent kinases (Cdks) and the anaphase-promoting complex/cyclosome (APC/C). Each Cdk or APC/C isoform has a large number of substrates, and the substrates of each isoform are modified in a specific order that leads to sequential substrate activation or inactivation. (biomedcentral.com)

Triggered by the mitotic1

• It has been suggested that once cells pass Start, Cln proteolysis is triggered by the mitotic cyclins Clb1, 2, 3 and 4 (ref. 6). (uky.edu)

Fission yeast1

• 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)

Complexes8

• Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
• Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
• A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
• This methodology can be applied to other protein complexes exhibiting group sumoylation. (bvsalud.org)
• Then, we use the uncertain model to identify dynamic protein complexes in the dynamic uncertain PPI networks. (biomedcentral.com)
• Since most proteins are only functional after assembly into protein complexes, protein complexes are critical in many biological processes [ 5 ]. (biomedcentral.com)
• 11 ] present COACH algorithm to identify protein complexes, which detects the core structure and attachments of complex respectively. (biomedcentral.com)
• It is necessary to construct dynamic PPI networks for both identifing protein complexes and further understanding molecular systems. (biomedcentral.com)

Mitosis5

• Kinase destruction is therefore implicated in the exit from mitosis rather than the entry into anaphase. (ox.ac.uk)
• The mitotic inducer nim1+ functions in a regulatory network of protein kinase homologs controlling the initiation of mitosis. (wikidata.org)
• Coupling of mitosis to the completion of S phase in Xenopus occurs via modulation of the tyrosine kinase that phosphorylates p34cdc2. (wikidata.org)
• Here we present an overview of the protein phosphatase 2A family's roles during mitosis. (encyclopedia.pub)
• The activator Cdc20 is then replaced by a second activator, Cdh1, and APC/C Cdh1 promotes complete degradation of M cyclin, followed by polo-like kinase 1, Aurora A, and other substrates, to complete mitosis and cytokinesis and drive progression into G1 [ 1 , 2 ]. (biomedcentral.com)

Cdc2 kinase1

• A multifunctional CDC2 kinase-related kinase that plays roles in transcriptional elongation, CELL DIFFERENTIATION , and APOPTOSIS . (nih.gov)

Subunit3

• It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
• In our previous research, we showed that the cyclin-dependent kinase regulatory subunit (CKS2) in maize (Zea mays L.) was induced by water deficit and cold stress. (edu.pl)
• In most metazoans, GCN2 is one of the four known kinases that phosphorylate eukaryotic initiation factor 2, α subunit (eIF2α) to inhibit translation initiation [ 19 ]. (biomedcentral.com)

Phosphorylation5

• This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (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)
• The inhibition of Torc1 by rapamycin mimics nutrient starvation and causes an array of physiological changes that include global changes in gene expression, phosphorylation/dephosphorylation of various factors, decreased cell growth, degradation of proteins, and ultimately cell cycle arrest in the G 1 phase [4, 9-11]. (researchsquare.com)
• The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5. (wikidata.org)

Mitotic cyclins1

• It is widely assumed that degradation of mitotic cyclins causes a decrease in mitotic cdc2/CDC28 kinase activity and thereby triggers the metaphase to anaphase transition. (ox.ac.uk)

Clb22

• About 24% of these proteins were phosphorylated more efficiently by Clb5-Cdk1 than Clb2-Cdk1. (nature.com)
• Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)

Substrate2

• 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)
• 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)

Degradation1

• The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)

Cln23

• Start is triggered by the cyclin- dependent kinase Cdc28 and three rate-limiting activators, the G1 cyclins Cln1, Cln2 and Cln3 (ref. 3). (uky.edu)
• Cyclin accumulation in G1 is driven in part by the cell-cycle-regulated transcription of CLN1 and CLN2, which peaks at Start. (uky.edu)
• However, we observed a sharp induction of the G 1 cyclin Cln2 (~ 3- to 4-fold) in the ste5Δ mutant within 30 mins of exposure to rapamycin. (researchsquare.com)

Transcriptional2

• Cln instability thus provides a means to couple Cln-Cdc28 activity to transcriptional regulation and protein synthetic rate in pre-Start G1 cells. (uky.edu)
• Cyclin D1 (Ccnd1) together with its binding partner Cdk4 act as a transcriptional regulator to control cell proliferation and migration, and abnormal Ccnd1·Cdk4 expression promotes tumour growth and metastasis. (bvsalud.org)

Subunits2

• The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. (wikipedia.org)
• Frequently, SUMO synergistically targets various subunits in a protein complex to modulate its function, leading to what has been defined as protein group sumoylation. (bvsalud.org)

Inhibits2

• In yeast, rapamycin inhibits the TORC1 kinase signaling pathway causing rapid alteration in gene expression and ultimately cell cycle arrest in G 1 through mechanisms that are not fully understood. (researchsquare.com)
• As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. (biomedcentral.com)

Promotes1

• We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. (bvsalud.org)

Dependent6

• Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene. (wikipedia.org)
• CDK4 is a member of the cyclin-dependent kinase family. (wikipedia.org)
• 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)
• Doonan JH, Kitsios G (2009) Functional evolution of cyclin-dependent kinases. (edu.pl)
• Egan EA, Solomon MJ (1998) Cyclin-stimulated binding of CKS proteins to cyclin-dependent kinases. (edu.pl)

Clb51

• The Clb5-specific targets include several proteins (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events. (nature.com)

Evolutionarily conserved2

• Giuliano G, Pichersky E, Malik V, Timko M, Scolnik P, Cashmore A (1988) An evolutionarily conserved protein binding sequence upstream of a plant light-regulated gene. (edu.pl)
• GCN2 is an evolutionarily conserved serine/threonine kinase that senses amino acid restriction through binding to uncharged tRNAs [ 18 ]. (biomedcentral.com)

Inhibitors1

• It is regulated by Cyclin D. Ribociclib are US FDA approved CDK4 and CDK6 inhibitors for the treatment of estrogen receptor positive/ HER2 negative advanced breast cancer. (wikipedia.org)

Pombe1

• This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. (wikipedia.org)

Regulator1

• Nuclear Cyclin D1 (Ccnd1) is a main regulator of cell cycle progression and cell proliferation. (bvsalud.org)

Progression3

• CLN transcription is modulated by physiological signals that regulate G1 progression, but it is unclear whether Cln protein stability is cell- cycle-regulated. (uky.edu)
• Protein sumoylation is a reversible posttranslational modification that controls multiple processes during cell cycle progression. (bvsalud.org)
• Progression through the cell cycle is accompanied by dramatic changes in cellular content and behavior, and involves a large number of proteins and processes. (biomedcentral.com)

Cdc61

• Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.com)

Mutants1

• The behaviour of esp1 mutants shows in addition that kinase destruction can occur in the absence of anaphase completion. (ox.ac.uk)

Nuclear2

• Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
• These attachment sites are linked to actin-bundles that surround the nucleus via an Ndj1-Mps3-Csm4 protein bridge that spans the inner and outer nuclear membranes. (biorxiv.org)

Activity3

• The execution of anaphase and the destruction of CDC28 kinase activity therefore appear to take place independently of one another. (ox.ac.uk)
• But here we show that G1 cyclins are unstable in G1 phase, and that Clb- Cdc28 activity is not needed for G1 cyclin turnover. (uky.edu)
• Overall, our findings molecularly link Ccnd1-Cdk4 to GABAARs activity in the central nervous system and highlight a novel role for this G1 cyclin in neuronal signalling. (bvsalud.org)

Destruction1

• Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. (ox.ac.uk)

Complex4

• The experimental results show that our approach can effectively deal with the uncertain data in dynamic uncertain PPI networks, and improve the performance for protein complex identification. (biomedcentral.com)
• A protein complex consists of a group of proteins and multiple PPIs at the same time and place, forming single multi-molecular machinery [ 4 ]. (biomedcentral.com)
• 10 ] propose CORE algorithm to identify protein-complex cores by calculating the p -values for all pairs of proteins. (biomedcentral.com)
• A protein complex is formed by a group of proteins at the same time, which interacted with each other by associated polypeptide chains. (biomedcentral.com)

Phase3

• activates Cdc28p kinase to promote the G1 to S phase trans. (ucsd.edu)
• Our data provide a new insight whereby rapamycin signaling via the Torc1 kinase may exploit the pheromone pathway to arrest cells in the G 1 phase. (researchsquare.com)
• The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes. (wikidata.org)

Activation1

• The expression of the STE5 gene and its encoded scaffold protein Ste5, required for the sequential activation of the MAPKs of the pheromone pathway, is greatly reduced in the H2B R95A mutant. (researchsquare.com)

Cdk41

• CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)

Pathway1

• The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. (biomedcentral.com)

Pairs1

• Fifty-nine module pairs that correlate with Cdc28 and other essential regulators were also identified. (biomedcentral.com)

Interaction2

• Recently, researchers have tried to integrate various dynamic information with static protein-protein interaction (PPI) networks to construct dynamic PPI networks. (biomedcentral.com)
• Over the past decade, yeast two-hybrid, mass spectrometry and other high-throughput experimental have generated a mass of protein-protein interaction (PPI) data. (biomedcentral.com)

Consists1

• Torc1 consists of either the Tor1 or the Tor2 kinase, a putative scaffold protein Kog1, Lst8, and Tco89 [4, 5]. (researchsquare.com)

Roberts1

• Roberts, J. M. Evolving ideas about cyclins. (nature.com)