• 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)
  • 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)
  • 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)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (novusbio.com)
  • Mitotic cyclins stably associate with CDC2 and function as regulatory subunits. (caslab.com)
  • 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 positive transcription elongation factor b (P-TEFb) (CDK9/cyclin T (CycT)) promotes mRNA transcriptional elongation through phosphorylation of elongation repressors and RNA polymerase II. (ox.ac.uk)
  • To understand the regulation of a transcriptional CDK by its cognate cyclin, we have determined the structures of the CDK9/CycT1 and free cyclin T2. (ox.ac.uk)
  • Group 3 cyclins (G1, G2 and I) may play a role distinct from either cell cycle or transcriptional regulation. (bdbiosciences.com)
  • 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)
  • The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. (ox.ac.uk)
  • Three sequential phosphorylation events on specific residues of p27, regulate the activity of these complexes and ultimately control cell cycle proliferation or arrest. (lu.se)
  • Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (bdbiosciences.com)
  • 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)
  • 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 a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II. (caslab.com)
  • Substrate specificity of the activated complex is mainly established by the associated cyclin within the complex. (wikipedia.org)
  • Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. (fhcrc.org)
  • There are distinct differences between CDK9/CycT1 and the cell cycle CDK CDK2/CycA manifested by a relative rotation of 26 degrees of CycT1 with respect to the CDK, showing for the first time plasticity in CDK cyclin interactions. (ox.ac.uk)
  • 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)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. (novusbio.com)
  • After A is degraded, concentrations of cyclin B peak in M phase and the complex will activate the different stages of mitosis. (jove.com)
  • 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)
  • 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)
  • 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)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • We show that Cdi4 can inhibit cyclin E function both in a yeast assay and in vitro. (fhcrc.org)
  • 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)
  • 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)
  • Immunocytochemistry/ Immunofluorescence: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on HeLa cell. (novusbio.com)
  • Immunohistochemistry-Paraffin: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on formalin-fixed paraffin-embedded human testis. (novusbio.com)
  • Sandwich ELISA: Cyclin H Antibody (1B8) [H00000902-M01] - Detection limit for recombinant GST tagged CCNH is approximately 1ng/ml as a capture antibody. (novusbio.com)
  • WB analysis of HeLa cell lysate using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • IHC-P analysis of human tonsil tissue using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • There are currently no references for Cyclin D1 antibody [RM241] (GTX33611) . (genetex.com)
  • 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)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • 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)
  • This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (novusbio.com)
  • 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)
  • 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)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • 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)
  • We hypothesize that a dynamic equilibrium between the dominant buried state and an transiently open, kinase-accessible state is present in the p27-cyclin A-CDK2 complex, and aim to test this hypothesis through the use of unbiased molecular dynamics and metadynamics simulations. (lu.se)
  • 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)
  • More recently, cyclins are being shown to have additional functions not restricted to cell cycle regulation. (bdbiosciences.com)
  • Like many cyclins, the expression of cyclin C oscillates throughout the cell cycle, with a peak observed during G1 phase. (bdbiosciences.com)
  • When this complex forms the CDK can phosphorylate a target protein which alters it's function and initiates the cell to advance to the next phase. (jove.com)
  • 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)
  • Generally, levels of a given cyclin are low during most of the cell cycle but abruptly increase at the checkpoint they most contribute to (G 1 cyclins are an exception, as they are required throughout the cell cycle). (jove.com)
  • 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)
  • solved the structure of human cyclin A-CDK2 complex to 2.3 Angstrom resolution. (wikipedia.org)
  • 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)
  • The CDK9/CycT1 interface is relatively sparse but retains some core CDK-cyclin interactions. (ox.ac.uk)
  • 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)
  • They must bind to a specific cyclin to be activated. (jove.com)
  • 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)
  • Notably, the first two post-translational modifications, which are required for the initial activation of these complexes, occur on solvent inaccessible (i.e., buried) tyrosine residues. (lu.se)
  • In most cases, when a cyclin is degraded, the CDK is inactivated, signaling the end of a particular phase. (jove.com)
  • 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)
  • p27 is a protein that binds to and prevents the activation of different G1 and S phase cyclin-CDK complexes. (lu.se)
  • Based on function, there are two general populations of CDK-cyclin complex structures, open and closed form. (wikipedia.org)
  • In this review, we evaluate the current literature on the function of cyclin F with an emphasis on its roles in cancer and neurodegeneration. (edu.au)
  • High resolution structures exist for approximately 25 CDK-cyclin complexes in total within the Protein Data Bank. (wikipedia.org)
  • The A allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. (iiarjournals.org)
  • This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. (novusbio.com)
  • Cyclin F dysfunction has been implicated in various forms of cancer and CCNF mutations were recently linked to familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia, offering a new lead to understanding the pathogenic mechanisms underlying neurodegeneration. (edu.au)
  • 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)