KinasesMitosisProteinsCDKsCdc2Complexes1997Requirement for cyclin2000CDK4GeneCCND1MitoticInhibitorsGenesOverexpressionLocalizationNuclearSpecificityCdk5Signaling pathwayPhosphorylation sitesImmunohistochemicalMotifWestern blot analysisExpressionSubstratesCdk1ImmunogenTranscriptionalAntibodyIdentifiesRegulatoryNucleusCDKN2AAlleleCell cycleSubstrateDependentFibroblastsActivationCancerStem cellsPhaseMetastasis
Kinases14
- 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 and cyclin-dependent kinases (cdks) are evolutionarily conserved proteins that are essential for cell-cycle control in eukaryotes. (bdbiosciences.com)
- A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. (umassmed.edu)
- Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases. (umassmed.edu)
- They are able to build complexes with cyclin-dependent kinases (CDKs) and regulate their activity ( 2 ). (iiarjournals.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)
- Cyclin-Dependent Kinases" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (jefferson.edu)
- Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (jefferson.edu)
- Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. (jefferson.edu)
- This graph shows the total number of publications written about "Cyclin-Dependent Kinases" by people in this website by year, and whether "Cyclin-Dependent Kinases" was a major or minor topic of these publications. (jefferson.edu)
- Below are the most recent publications written about "Cyclin-Dependent Kinases" by people in Profiles. (jefferson.edu)
- Mammalian Cdc25 phosphatase is responsible for the dephosphorylation of Cdc2 and other cyclin-dependent kinases at Thr14 and Tyr15, thus activating the kinase and allowing cell cycle progression. (embl.de)
- Cyclins function as regulators of CDK kinases. (genetex.com)
Mitosis5
- 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)
- 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)
- 1992 In addition cyclin A2 was postulated to play a role in access of cells into mitosis (Swenson et al. (immune-source.com)
- Activation of the Cyclin B/Cdc2 kinase complex triggers entry into mitosis in all eukaryotic cells. (duke.edu)
- In mitosis, Cyclin B1 undergoes phosphorylation at several sites, a subset of which have been proposed to play a role in Cyclin B1 accumulation in the nucleus. (duke.edu)
Proteins4
- It is regulated by cyclins, more specifically by Cyclin D proteins and Cyclin-dependent kinase inhibitor proteins. (wikipedia.org)
- Cyclins are a group of proteins that play a key role in the control and regulation of the cell cycle. (iiarjournals.org)
- We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
- These results suggest that alterations in the cell cycle proteins, cyclin D1, cdk4, p16INK4a, and Rb, may play a role in the acquisition of autonomous growth by adenomas. (jax.org)
CDKs1
- 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)
Cdc22
- Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (bdbiosciences.com)
- Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1. (duke.edu)
Complexes4
- A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
- In these compartments cyclin A-Cdk complexes are expressed at particularly high levels which may render stem cells dependent on cyclin A. INTRODUCTION Replication of genetic material during cell division in Metazoan organisms is thought to be driven by cyclin A. Cyclin A was the first cyclin cloned in any organism (Swenson et al. (immune-source.com)
- Consequently, most cyclin-dependent kinase (Cdk)/cyclin complexes are localized to the nucleus when active. (duke.edu)
- TSH and EGF+serum also induced a previously undescribed nuclear translocation of cdk4, the assembly of precipitable cyclin D3-cdk4 complexes, and the Rb kinase activity of these complexes. (ac.be)
19972
- 1997 These studies have led to the current model that this "core" components of the cell cycle machinery (cyclins A and B) symbolize XI-006 absolutely essential elements of the cell cycle engine (Hochegger et al. (immune-source.com)
- 1997 In the work explained below we decided to revisit the requirement for cyclin A function in cell proliferation using conditional cyclin A knockout mice. (immune-source.com)
Requirement for cyclin1
- DI-fusion Table of Contents: A requirement for cyclin. (ac.be)
20001
- Physique 1 Generation of Cyclin A2f/f Mice In order to verify that deletion of the "floxed" cyclin A2 sequences resulted in a functionally null allele we crossed cyclin A2f/f mice with a "deleter" Meox2-Cre strain (Tallquist and Soriano 2000 and generated cyclin A2? (immune-source.com)
CDK48
- The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
- This study examined the involvement of D-type G1 cyclins and their associated cyclin-dependent kinase (cdk4) in the cAMP-dependent G1 phase progression of dog thyroid cells. (ac.be)
- It was found to reflect both the unmasking of an epitope of cyclin D3 close to its domain of interaction with cdk4, and the nuclear translocation of cyclin D3. (ac.be)
- The expression of cyclin D1, cdk4, p16INK4a, and Rb protein was examined by immunohistochemistry in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced mouse lung tumors. (jax.org)
- Immunohistochemical staining revealed exclusive nuclear staining of both cyclin D1 and cdk4 that was light to moderate in normal mouse lung tissues, but intense in lung adenomas and adenocarcinomas. (jax.org)
- Western blot analysis confirmed the increased expression of cyclin D1 and cdk4 in lung tumors compared to normal lung. (jax.org)
- 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)
- 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)
Gene10
- 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)
- 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)
- 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)
- 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)
- 1983 Subsequently cyclin A genes have been found in all multicellular organisms including humans (Pines and Hunter 1990 While only a single cyclin A gene is present in the genomes of and cultured fibroblasts XI-006 or other cell types blocked DNA synthesis consistent with the essential function for cyclin A in DNA replication (Girard et al. (immune-source.com)
- RESULTS Generation and Characterization of Conditional Cyclin A2 Knockout Mice To obtain a conditional cyclin A2 allele we inserted sites into the first and seventh intron of the murine cyclin A2 gene (Physique 1A). (immune-source.com)
- The gene-targeting construct was launched into embryonal stem (ES) cells and heterozygous cyclin A2f/+ (Af denotes XI-006 the "floxed" allele) ES were obtained through homologous recombination (Figures 1A and 1B). (immune-source.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 throughout the cell cycle. (genetex.com)
- The molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). (medscape.com)
CCND12
- 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)
- Genetic alterations of BCL2 (B-cell CLL/lymphoma 2), MYC [v-myc myelocytomatosis viral oncogene homolog (avian)] and CCND1 (cyclin D1) are the most frequently found alterations in human B-cell lymphomas. (haematologica.org)
Mitotic4
- 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. (genetex.com)
- The first of the three major projects involves understanding the function of the A and E-type cyclins during the mitotic and meiotic cell cycles mainly during spermatogenesis but also in oogenesis. (columbia.edu)
- We have demonstrated that cyclin A1 is essential for the progression of spermatocytes into the first meiotic division, that cyclin A2 is required for mitotic divisions of male germ cell stem cells, and that the E-type cyclins have unexpected function during meiosis, notably in the maintenance of telomere integrity. (columbia.edu)
Inhibitors5
- the cyclin D. The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (wikipedia.org)
- Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
- Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. (koreamed.org)
- Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. (koreamed.org)
- Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
Genes3
- Orthologous to several human genes including CCNB1 (cyclin B1). (nih.gov)
- Genes & Development 12, no. 14 (July 1998): 2131-43. (duke.edu)
- CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. (cancercentrum.se)
Overexpression6
- Overexpression of cyclin D1 has been found in a variety of malignancies and is suggested to be related to tumor progression. (elsevierpure.com)
- We immunohistochemically investigated the overexpression of cyclin D1 protein in 92 laryngeal carcinomas. (elsevierpure.com)
- Twenty-eight (30.4%) of the carcinoma specimens showed overexpression of cyclin D1. (elsevierpure.com)
- However, the overexpression of cyclin D1 in patients with local recurrence was significantly higher than in patients with no recurrence. (elsevierpure.com)
- G?ller M, Toualbi-Abed K, Legrand A, Michel L, Mauviel A, Bernuau D, Daniel F. c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1. (jefferson.edu)
- In occasional cells, this crossing over may lead to increased 12p copy number and overexpression of cyclin D2. (medscape.com)
Localization7
- F-box protein specificity for g1 cyclins is dictated by subcellular localization. (umassmed.edu)
- Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. (duke.edu)
- We show here that the previously characterized cytoplasmic retention sequence of Cyclin B1, responsible for its interphase cytoplasmic localization, is actually an autonomous nuclear export sequence, capable of directing nuclear export of a heterologous protein, and able to bind specifically to the recently identified export mediator, CRM1. (duke.edu)
- We propose that the observed cytoplasmic localization of Cyclin B1 during interphase reflects the equilibrium between ongoing nuclear import and rapid CRM1-mediated export. (duke.edu)
- In this study, we examined the expression and subcellular localization of cyclin-dependent kinase 5 (Cdk5), cyclin D1, and cyclin E in Leydig and Sertoli cell lines that were cultured with 7.5, 1.0, 0.5, or 0% serum (mixture of a 2:1 ratio of horse serum and fetal bovine serum) and in the developing rat testis to verify the possible functions of Cdk5, cyclin D1, and cyclin E in the testis. (elsevierpure.com)
- Immunohistochemical localization of Cdk5, cyclin D1, and cyclin E in 1-week- old and adult rat testes revealed expression in both Leydig and Sertoli cells. (elsevierpure.com)
- Localization to the chromocenters is mediated by an N-terminal domain, in addition we find that this domain may be involved in cyclin binding. (uni-bielefeld.de)
Nuclear6
- 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)
- In support of this hypothesis, we found that treatment of cells with leptomycin B, which disrupted Cyclin B1-CRM1 interactions, led to a marked nuclear accumulation of Cyclin B1. (duke.edu)
- thus, we propose that Cyclin B1 phosphorylation at the G2/M transition prevents its interaction with CRM1, thereby reducing nuclear export and facilitating nuclear accumulation. (duke.edu)
- However, TSH stimulation enhanced the nuclear detection of cyclin D3. (ac.be)
- Immunohistochemical staining for Cdk5 and cyclin E revealed nuclear and cytoplasmic distribution, both in TM3 and TM4 cells. (elsevierpure.com)
- In Cyclin A2-depleted normal murine mammary gland (NMuMG) cells expressing RasV12, we found that beta-catenin was liberated from the cell membrane and cell-cell junctions and underwent nuclear translocation and activation. (cnrs.fr)
Specificity3
- 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)
- Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
- Tissue specificity of cyclin B expression in D. melanogaster]. (nih.gov)
Cdk53
- Cdk5 is named after its structural similarity to members of the serine/threonine cyclin-dependent kinase family. (frontiersin.org)
- The abundance of Cdk5 and cyclin E in the Leydig cell line, TM3, was significantly reduced at low serum concentrations. (elsevierpure.com)
- In contrast, serum concentration had no effect on Cdk5 and cyclin E levels in the Sertoli cell line, TM4. (elsevierpure.com)
Signaling pathway1
- Pope PA, Bhaduri S, Pryciak PM. Regulation of cyclin-substrate docking by a G1 arrest signaling pathway and the Cdk inhibitor Far1. (umassmed.edu)
Phosphorylation sites1
- This protein also contains an ATP-binding pocket, inhibitory and activating phosphorylation sites, a PSTAIRE-like cyclin-binding domain and an activating T-loop motif. (wikipedia.org)
Immunohistochemical1
- Cyclin D1 immunohistochemical staining is considered to be a useful marker for predicting tumor recurrence. (elsevierpure.com)
Motif3
- After binding the Cyclin in the PSTAIRE helix, the protein changes its conformational structure to expose the phosphorylation motif. (wikipedia.org)
- Bandyopadhyay S, Bhaduri S, ?rd M, Davey NE, Loog M, Pryciak PM. Comprehensive Analysis of G1 Cyclin Docking Motif Sequences that Control CDK Regulatory Potency In?Vivo. (umassmed.edu)
- 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)
Western blot analysis2
- Western blot analysis of cyclin C in NIH 3T3 mouse fibroblasts. (bdbiosciences.com)
- Cyclin D1 was detected by western blot analysis in TM4 cells only, and its abundance was serum dose dependent. (elsevierpure.com)
Expression3
- Like many cyclins, the expression of cyclin C oscillates throughout the cell cycle, with a peak observed during G1 phase. (bdbiosciences.com)
- Fibroblasts were isolated from cyclin A1-/-A2f/f embryos cultured and transduced with Cre-expressing viruses thereby ablating all cyclin A expression (Figures 1D and S1A). (immune-source.com)
- Unlike epidermal growth factor (EGF)+serum and other cAMP-independent mitogens, TSH did not induce the accumulation of cyclins D1 and D2 and partially inhibited the basal expression of the most abundant cyclin D3. (ac.be)
Substrates1
- Bhaduri S, Valk E, Winters MJ, Gruessner B, Loog M, Pryciak PM. A docking interface in the cyclin Cln2 promotes multi-site phosphorylation of substrates and timely cell-cycle entry. (umassmed.edu)
Cdk12
- Targets of the cyclin-dependent kinase Cdk1. (nature.com)
- Cyclin A degradation employs preferentially used lysines and a cyclin box function other than Cdk1 binding. (nih.gov)
Immunogen1
- 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)
Transcriptional2
- Group 3 cyclins (G1, G2 and I) may play a role distinct from either cell cycle or transcriptional regulation. (bdbiosciences.com)
- A subset of cyclins may also function as transcriptional regulators. (umassmed.edu)
Antibody4
- Here, microinjections of a cyclin D3 antibody showed that cyclin D3 is essential in the TSH/ cAMP-dependent mitogenesis, but not in the pathway of growth factors that induce cyclins D1 and D2. (ac.be)
- 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)
Identifies1
- No. 558903) was titrated from 1:4000 to 1:12,000 (lanes 1 to 3) and identifies cyclin at ~ 36 kD. (bdbiosciences.com)
Regulatory1
- cyclin-dependent kinase 5, regulatory. (wikigenes.org)
Nucleus1
- 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)
CDKN2A1
- Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. (koreamed.org)
Allele4
- The A allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. (iiarjournals.org)
- 2003 Cyclin A2f/f mice were viable and phenotypically normal (data not shown) consistent with our expectation that this "floxed" cyclin A2 allele is usually functionally wild-type. (immune-source.com)
- denotes the deleted cyclin A2 allele). (immune-source.com)
- Hence deletion of the "floxed" cyclin A2 sequences converts the conditional cyclin A2 allele into a functionally null allele. (immune-source.com)
Cell cycle6
- In mammalian cells, cell cycle is activated by CDK6 in the early G1 phase through interactions with cyclins D1, D2 and D3. (wikipedia.org)
- More recently, cyclins are being shown to have additional functions not restricted to cell cycle regulation. (bdbiosciences.com)
- It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21 Cip/Waf and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. (nature.com)
- Cyclin A the first cyclin ever cloned is regarded as an essential component of the cell cycle engine. (immune-source.com)
- Analyses of Cyclin A-null Fibroblasts We next derived fibroblasts from conditional cyclin A2 knockout embryos and cultured them culture (Physique 2A) and normally re-entered the cell cycle from quiescence (Physique 2B). (immune-source.com)
- However analyses of cell cycle progression using propidium iodide and anti-BrdU staining revealed that ablation of cyclin A2 increased the portion of cells in S and G2/M phases with concomitant decrease in the G1 populace (Figures 2C and 2D). (immune-source.com)
Substrate1
- 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)
Dependent2
- Enables cyclin-dependent protein serine/threonine kinase regulator activity. (nih.gov)
- Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. (jefferson.edu)
Fibroblasts2
- 1986 and injection of anti-cyclin A2 antibodies into cultured fibroblasts or inhibiting cyclin A2 function by p21Cip1 during the G2 phase blocked G2?M phase progression (Furuno et al. (immune-source.com)
- Fibroblasts To rule out the possible contribution from cyclin A1 we crossed cyclin A2f/f mice with cyclin A1-null animals (Liu et al. (immune-source.com)
Activation1
Cancer2
- Examining the role of cyclin D1 in breast cancer. (jefferson.edu)
- Cyclin D1 dysregulation and differential inactivation of p16INK4a and Rb have been observed in human lung cancer. (jax.org)
Stem cells1
- cyclin A function was essential for proliferation of hematopoietic and embryonal stem cells. (immune-source.com)
Phase1
- We found that cells lacking all A-type cyclins proliferated normally in culture (Physique XI-006 2A) and joined the S phase from G0. (immune-source.com)