KinasesCDKsPhosphorylationSpecificityCDK2Cdc2 protein kinaseMitotic cyclinDegradationSubstrateCdk1DependentCDK9Transcriptional regulationCdk4GenesSerineBindsDrosophilaInhibitionSubunitGeneReplicationProteinsYeastEukaryoticAntibodyMolecularActivationRegulationLocalizationMechanismCompoundsActivityPolymeraseExpression
Kinases13
- Once cyclin-dependent kinases bind to cyclin, the formed complex is in an activated state. (wikipedia.org)
- Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. (rcsb.org)
- Aberrant control of cyclin-dependent kinases (CDKs) is a central feature of the molecular pathology of cancer. (rcsb.org)
- Increasing numbers of sequence and biochemical data show the involvement of cyclin-dependent kinases (CDKs) and cyclins in regulation of the cell cycle progression in higher plants. (bibbase.org)
- The present yeast two-hybrid analyses showed differential interaction between defined D-type cyclins and Cdc2Ms kinases functioning in G2/M phases. (bibbase.org)
- article{meszaros_multiple_2000, title = {Multiple cyclin-dependent kinase complexes and phosphatases control {G2}/{M} progression in alfalfa cells}, volume = {43}, issn = {1573-5028}, url = {https://doi.org/10.1023/A:1006412413671}, doi = {10/cb64mn}, abstract = {Reversible phosphorylation of proteins by kinases and phosphatases plays a key regulatory role in several eukaryotic cellular functions including the control of the division cycle. (bibbase.org)
- We therefore evaluated the effects of SRIH and a selective SSTR2 agonist on cell cycle protein expression, mainly focusing on cyclin D1 and its associated kinases. (unife.it)
- Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (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)
- Cyclins function as regulators of CDK kinases. (novusbio.com)
- The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). (novusbio.com)
- Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
- As a biologically important example we have studied the complex formed by cyclins and cyclin-dependent kinases (CDKs), which play an essential role in the control of the eukaryotic cell cycle. (lu.se)
CDKs5
- 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)
- 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)
Phosphorylation12
- 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)
- 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)
- The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol and regulation by phosphorylation. (ox.ac.uk)
- 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)
- Moreover, our data show an increase in glycogen synthase kinase-3beta activity, which triggers phosphorylation-dependent cyclin D1 degradation. (unife.it)
- 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)
- 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)
- 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)
Specificity5
- Substrate specificity of the activated complex is mainly established by the associated cyclin within the complex. (wikipedia.org)
- Tissue specificity of cyclin B expression in D. melanogaster]. (nih.gov)
- Drosophila Cdi4 is a p21/p27/p57-like cyclin-dependent kinase inhibitor with specificity for cyclin E complexes. (fhcrc.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)
CDK29
- solved the structure of human cyclin A-CDK2 complex to 2.3 Angstrom resolution. (wikipedia.org)
- 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)
- 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)
- Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
- Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1. (duke.edu)
- Entry into the S phase in animal cells is regulated to a large extent by the cyclin E-CDK2 kinase complex. (news-medical.net)
- Cyclin E-CDK2 is also needed for the DNA replication and centrosome duplication events in S phase. (news-medical.net)
- 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)
- 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)
Cdc2 protein kinase1
- cdc2 protein kinase is complexed with both cyclin A and B: Evidence for proteolytic inactivation of MPF. (cshlpress.com)
Mitotic cyclin3
- Interaction between alfalfa mitotic cyclin (Medsa;CycB2;1) and a kinase partner has been reported previously. (bibbase.org)
- 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)
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)
- 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)
- Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (novusbio.com)
Substrate2
- 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)
Cdk13
- Targets of the cyclin-dependent kinase Cdk1. (nature.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)
- In ER+ cancer cells, PIP5K1α acted on pSer-473 AKT, and was in complexes with VEGFR2, serving as co-factor of ER-alpha to regulate activities of target genes including cyclin D1 and CDK1. (lu.se)
Dependent15
- 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)
- 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)
- This gene encodes the cyclin-dependent kinase inhibitor p21(WAF1/Cip1), a factor implicated in cell cycle, senescence, and cancer. (ed.ac.uk)
- RIP140 is required for ERα-complex formation, ERα-mediated gene expression, and ERα-dependent breast cancer cell proliferation. (aacrjournals.org)
- Consequently, most cyclin-dependent kinase (Cdk)/cyclin complexes are localized to the nucleus when active. (duke.edu)
- Characterization of the Cyclin Dependent Kinase Complex Bur1-2 and its Interaction with RPA. (uni-muenchen.de)
- ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. (cshlpress.com)
- 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)
CDK93
- 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)
- The CDK9/CycT1 interface is relatively sparse but retains some core CDK-cyclin interactions. (ox.ac.uk)
- 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)
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)
- The enzyme is activated by its interaction with CYCLIN C and plays a role in transcriptional regulation by phosphorylating RNA POLYMERASE II. (bvsalud.org)
Cdk42
- 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)
- 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)
Genes4
- Orthologous to several human genes including CCNB1 (cyclin B1). (nih.gov)
- Cis and trans interactions between genes encoding PAF1 complex and ESCRT machinery components in yeast. (thebiogrid.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)
- 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)
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)
Binds2
Drosophila3
- 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)
- We tested interactions between Drosophila cyclins and a panel of hundreds of previously identified proteins. (fhcrc.org)
- One of the connections we identified was the interaction between cyclin E and a novel Drosophila protein, Cdi4. (fhcrc.org)
Inhibition1
Subunit1
- 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)
Gene1
- 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)
Replication1
- 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)
Proteins2
- 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)
Yeast2
- We show that Cdi4 can inhibit cyclin E function both in a yeast assay and in vitro. (fhcrc.org)
- Characterization of a myosin transport complex from yeast. (uni-muenchen.de)
Eukaryotic1
Antibody4
- 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)
- Western Blot: Cyclin H Antibody (1B8) [H00000902-M01] - CCNH monoclonal antibody (M01), clone 1B8 Analysis of CCNH expression in HeLa. (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)
Molecular1
- NGL viewer: web-based molecular graphics for large complexes. (icr.ac.uk)
Activation3
- 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)
- 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)
- 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)
Regulation1
- The functional regulation of cells is a complex and dynamic process. (nature.com)
Localization1
Mechanism1
- From these simulations we aim to obtain a more detailed understanding of the conformational ensemble of this complex and the binding and release mechanism of p27, as well as to be able to calculate the free energy difference between the bound and unbound states. (lu.se)
Compounds1
- and discover new compounds (parkamycins A and B) with complex biological activity. (eurekalert.org)
Activity2
- p27 regulates G1 /S transition by abrogating the activity of cyclin/CDK complexes. (umass.edu)
- Another central challenge is identifying the molecule or molecules driving biological activity in a complex mixture from nature. (eurekalert.org)
Polymerase1
- This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (novusbio.com)
Expression2
- 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)