• 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Initiation of DNA replication during the mitotic cell cycle requires the activation of a cyclin-dependent protein kinase (CDK). (ox.ac.uk)
  • 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)
  • In budding fungus activation of S-phase Clbp-Cdc28p proteins kinase depends upon the last activation of Cdc28p connected with another course of G1 cyclins Cln1-3p. (bio2009.org)
  • 3) Clnp-Cdc28p protein kinase phosphorylates the cyclin-dependent kinase inhibitor (CKI) Sic1p focusing on it for ubiquitin-mediated degradation via the ubiquitin-conjugating enzyme Cdc34p (Schwob et al. (bio2009.org)
  • We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
  • In late-G1, Whi5 is rapidly hyper-phosphorylated by Cln1,2 in complex with the cyclin-dependent kinase Cdk1. (bvsalud.org)
  • Substrate specificity of the activated complex is mainly established by the associated cyclin within the complex. (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)
  • 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)
  • Clb5 specificity depended on an interaction between a hydrophobic patch in Clb5 and a short sequence in the substrate (the RXL or Cy motif). (nature.com)
  • 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 2: Clb5 specificity depends on an interaction between the Clb5 hydrophobic patch and an RXL motif in the substrate. (nature.com)
  • Figure 3: Clb5-specific substrate phosphorylation occurs in vivo . (nature.com)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • We show experimentally that increased expression of the early APC/C Cdc20 substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. (biomedcentral.com)
  • 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)
  • 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)
  • About 24% of these proteins were phosphorylated more efficiently by Clb5-Cdk1 than Clb2-Cdk1. (nature.com)
  • Thus, Clb5 and Clb2 use distinct mechanisms to enhance the phosphorylation of S-phase and M-phase substrates. (nature.com)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • Figure 1: Identification of Clb5-specific Cdk1 substrates in budding yeast. (nature.com)
  • The B-type cyclins Clb5 and Clb6 are the primary activators of the S phase function of the budding yeast CDK Cdc28. (ox.ac.uk)
  • 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)
  • In Lamivudine IC50 fission candida the CKI encoded from the rum1 gene takes on a crucial part in regulating the cyclin B-CDK activity in G1 (Moreno and Nurse 1994 blue right-pointing triangle). (bio2009.org)
  • 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)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • 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)
  • High resolution structures exist for approximately 25 CDK-cyclin complexes in total within the Protein Data Bank. (wikipedia.org)
  • The difference between the forms lies within the binding of cyclin partners where closed form complexes have CDK-cyclin binding at both the C and N-termini of the activation loop of the CDK, whereas the open form partners bind only at the N-terminus. (wikipedia.org)
  • 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)
  • The second option entails ubiquitin-mediated degradation of B-type cyclins which requires the cyclosome (Sudakin et al. (bio2009.org)
  • The Clb5-specific targets include several proteins (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events. (nature.com)
  • CLB5 and CLB6 are required for premeiotic DNA replication and activation of the meiotic S/M checkpoint. (ox.ac.uk)
  • Diploid clb5/clb5 clb6/clb6 mutants are unable to perform premeiotic DNA replication. (ox.ac.uk)
  • Although cells that lack clb5 and clb6 are unable to activate the meiotic DNA replication checkpoint, they do possess an intact DNA damage checkpoint which can restrain chromosome segregation in the face of DNA damage. (ox.ac.uk)
  • We conclude that CLB5 and CLB6 are essential for premeiotic DNA replication and, consequently, for activation of a meiotic DNA replication checkpoint. (ox.ac.uk)
  • The systems ensuring the timely inactivation and activation of cyclin B-CDK in G1 have been studied primarily in budding candida. (bio2009.org)
  • 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)
  • solved the structure of human cyclin A-CDK2 complex to 2.3 Angstrom resolution. (wikipedia.org)
  • Based on function, there are two general populations of CDK-cyclin complex structures, open and closed form. (wikipedia.org)
  • However, in mitotically growing cells this role can be fulfilled by the other B-type cyclins Clb1-Clb4. (ox.ac.uk)
  • 1997). Hyperphosphorylation of the N-terminal domain of Cdc25 regulates activity toward cyclin B1/cdc2 but not cyclin A/cdk2. (sdbonline.org)
  • Assembly of Cdc2/cyclin B heterodimers promotes phosphorylation and inactivation of Cdc2 subunit ( left ). (comprehensivephysiology.com)
  • The difference between the forms lies within the binding of cyclin partners where closed form complexes have CDK-cyclin binding at both the C and N-termini of the activation loop of the CDK, whereas the open form partners bind only at the N-terminus. (wikipedia.org)
  • However, in mitotically growing cells this role can be fulfilled by the other B-type cyclins Clb1-Clb4. (ox.ac.uk)
  • Furthermore, the two B type cyclins such as Clb1 and Clb2 are expressed when chromosome replication is completed by cells and entered into G 2. (blogspot.com)
  • NAP1 acts with Clb1 to perform mitotic functions and to suppress polar bud growth in budding yeast. (sdbonline.org)
  • CLB5 and CLB6 are required for premeiotic DNA replication and activation of the meiotic S/M checkpoint. (ox.ac.uk)
  • The B-type cyclins Clb5 and Clb6 are the primary activators of the S phase function of the budding yeast CDK Cdc28. (ox.ac.uk)
  • Diploid clb5/clb5 clb6/clb6 mutants are unable to perform premeiotic DNA replication. (ox.ac.uk)
  • Although cells that lack clb5 and clb6 are unable to activate the meiotic DNA replication checkpoint, they do possess an intact DNA damage checkpoint which can restrain chromosome segregation in the face of DNA damage. (ox.ac.uk)
  • We conclude that CLB5 and CLB6 are essential for premeiotic DNA replication and, consequently, for activation of a meiotic DNA replication checkpoint. (ox.ac.uk)
  • The transcribed proteins Clb5 and Clb6 get accumulated due to APC inactivation, which would then result in the degradation of these cyclins. (blogspot.com)
  • These complexes combined with Clb5 and Clb6 activate the origin of replication throughout the S phase. (blogspot.com)
  • Pds1p of budding yeast has dual roles: inhibition of anaphase initiation and regulation of mitotic exit. (vt.edu)
  • Orchestrating the cell cycle in yeast: sequential localization of key mitotic regulators at the spindle pole and the bud neck. (vt.edu)
  • 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)
  • Feedback regulation of the MBF transcription factor by cyclin Cig2. (vt.edu)
  • 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)
  • 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)
  • 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)
  • Based on function, there are two general populations of CDK-cyclin complex structures, open and closed form. (wikipedia.org)