• At the cellular level, the process is controlled by different levels of cyclin-dependent kinases (Cdks) and their partner cyclins. (wikipedia.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)
  • We show that it is possible to predict proteins that are likely to be targets of CDKs in S. cerevisiae by searching for proteins that contain clustered matches to the CDK consensus. (biomedcentral.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)
  • Cell division is thought to be initiated by cyclin-dependent kinases (Cdks) inactivating key transcriptional inhibitors. (bvsalud.org)
  • Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the CDK2 gene. (wikipedia.org)
  • The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. (wikipedia.org)
  • It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. (wikipedia.org)
  • This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. (wikipedia.org)
  • Cyclin-dependent kinase 2 is structured in two lobes. (wikipedia.org)
  • Cdk2 is capable of binding to many different cyclins, including cyclins A, B, E, and possibly C. Recent studies suggest Cdk2 binds preferentially to cyclins A and E, while Cdk1 prefers cyclins A and B. Cdk2 becomes active when a cyclin protein (either A or E) binds at the active site located between the N and C lobes of the kinase. (wikipedia.org)
  • Prior to G1 phase, levels of Cdk4 and Cdk6 increase along with cyclin D. This allows for the partial phosphorylation of Rb, and partial activation of E2F at the beginning of G1 phase, which promotes cyclin E synthesis and increased Cdk2 activity. (wikipedia.org)
  • 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)
  • 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)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • 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)
  • 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)
  • We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
  • 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)
  • Progression through the cell cycle depends on the phosphorylation of key substrates by cyclin-dependent kinases. (bvsalud.org)
  • In late-G1, Whi5 is rapidly hyper-phosphorylated by Cln1,2 in complex with the cyclin-dependent kinase Cdk1. (bvsalud.org)
  • In budding yeast, the G1 cyclin Cln3-Cdk1 complex is thought to directly phosphorylate the Whi5 protein, thereby releasing the transcription factor SBF and committing cells to division. (bvsalud.org)
  • 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 APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • 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)
  • Thus, our work shows how Whi5 phosphorylation regulates the G1/S transition and how it is required for timely progression through S/G2/M phases and not only G1 as previously thought. (bvsalud.org)
  • Figure 1: Identification of Clb5-specific Cdk1 substrates in budding yeast. (nature.com)
  • Thus, Clb5 and Clb2 use distinct mechanisms to enhance the phosphorylation of S-phase and M-phase substrates. (nature.com)
  • Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
  • Finally, our data suggest that additional cellular BIKE interactors implicated in the host immune and stress responses and the ubiquitin proteasome system might also be candidate phosphorylation substrates of BIKE. (bvsalud.org)
  • In conclusion, these findings reveal cellular substrates and pathways regulated by the understudied Numb-associated kinase enzyme BIKE, a mechanism for CLINT1 regulation, and control of DENV infection via BIKE signaling, with potential implications for cell biology, virology, and host-targeted antiviral design. (bvsalud.org)
  • Phosphorylation of Clb5-specific targets during S phase was reduced by replacing Clb5 with Clb2 or by mutating the substrate RXL motif, confirming the importance of Clb5 specificity in vivo . (nature.com)
  • Figure 3: Clb5-specific substrate phosphorylation occurs in vivo . (nature.com)
  • We report that Whi5 is a poor substrate of Cln3-Cdk1, which instead phosphorylates the RNA polymerase II subunit Rpb1's C-terminal domain on S5 of its heptapeptide repeats. (bvsalud.org)
  • This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, also known as Cdk1 in humans. (wikipedia.org)
  • We also show that human CDK targets are enriched for proteins that contain clustered consensus matches and, by searching human cell cycle genes, we predict several putative CDK targets, including the human orthologs of Schizosaccharomyces pombe CDC5 (CDC5L) and S. cerevisiae Cdc20p (CDC20). (biomedcentral.com)
  • The Clb5-specific targets include several proteins (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events. (nature.com)
  • Moreover, the rapidity of Whi5 hyper-phosphorylation in late G1 depends on 'priming' sites that dock the Cks1 subunit of Cln1,2-Cdk1 complexes. (bvsalud.org)
  • Cdc55 counteracts the Cdk1 phosphorylation of the APC/C subunit Cdc16 [ 11 ] [ 10 ] , keeping the spindle checkpoint assembly (SAC) active until the cell is prepared for anaphase. (encyclopedia.pub)
  • Cln3-Cdk1 binds SBF-regulated promoters and Cln3's function can be performed by the canonical S5 kinase Ccl1-Kin28 when synthetically recruited to SBF. (bvsalud.org)
  • We subsequently validated 19 of 47 putative BIKE interactors using mammalian cell-based protein-protein interaction assays. (bvsalud.org)
  • Cdk1 is now believed to compensate for many aspects of Cdk2 deletion, except for meiotic function. (wikipedia.org)
  • Here we identified Nup2 in a pool of enriched proteins that co-purify with tagged Ndj1 from meiotic cell extracts. (biorxiv.org)
  • Because of the low specificity of the CDK consensus, however, databases of protein sequences are expected to contain large numbers of matches by chance. (biomedcentral.com)
  • The signaling pathways and cellular functions regulated by the four Numb-associated kinases are largely unknown. (bvsalud.org)
  • Our findings revealed that CLINT1 phosphorylation mediates its binding to the DENV nonstructural 3 protein and subsequently promotes DENV assembly and egress. (bvsalud.org)
  • Cdc14 is kept sequestered in the nucleolus by its binding to the nucleolar protein Net1 during most of the cell cycle. (encyclopedia.pub)
  • 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)
  • The precise regulations of pre-RC protein levels and assembly are effective ways to prevent reassembly of de novo MCM2-7 onto the replicated origins to re-license and re-replicate the genomic DNA in the subsequent phases of the same cell cycle ( Figure 1) . (intechopen.com)
  • Hyper-phosphorylation is crucial for Whi5 nuclear export, normal cell size, full expression of SBF target genes, and timely progression through both the G1/S transition and S/G2/M phases. (bvsalud.org)
  • Our data suggest that regulatory modules may exist in protein sequence as clusters of short sequence motifs. (biomedcentral.com)
  • Complex interactions between proteins and DNA within the cell allow genomic DNA to be passed to daughter cells. (wikipedia.org)
  • Interactions between cells and extracellular matrix proteins allow new cells to be incorporated into existing tissues. (wikipedia.org)
  • A beta-hairpin comprising the nuclear localization sequence sustains the self-associated states of nucleosome assembly protein 1. (colorado.edu)
  • 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)
  • The role of this protein in G1-S transition has been recently questioned as cells lacking Cdk2 are reported to have no problem during this transition. (wikipedia.org)
  • Mutation of 7 sites removed G1 hypo-phosphorylation, increased cell size, and delayed the G1/S transition. (bvsalud.org)
  • This hyper-phosphorylation inactivates Whi5 and excludes it from the nucleus. (bvsalud.org)
  • To do this, we first identified the 19 Whi5 sites that are appreciably phosphorylated and then determined which of these sites are responsible for G1 hypo-phosphorylation. (bvsalud.org)
  • The significance of this movement is that it brings the side chain of Glu 51, which belongs to a triad of catalytic site residues conserved in all eukaryotic kinases, into the catalytic site. (wikipedia.org)
  • Protein kinases are ubiquitous components of cellular signalling networks [ 1 ]. (biomedcentral.com)