• Cyclins themselves have no enzymatic activity but have binding sites for some substrates and target the Cdks to specific subcellular locations. (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)
  • Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle. (wikipedia.org)
  • 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)
  • Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C) , two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. (sdbonline.org)
  • A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2 . (online-medical-dictionary.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)
  • cyclin-dependent kinase 5, regulatory. (wikigenes.org)
  • Here, we investigated the mechanism by which cyclin I safeguards against apoptosis and found that cyclin I bound and activated cyclin-dependent kinase 5 (Cdk5) in isolated mouse podocytes and neurons. (jci.org)
  • Cyclin-dependent kinase 5 and its activator p35 disrupt Munc18a-syntaxin 1 binding, thereby promoting synaptic vesicle fusion during exocytosis. (eur.nl)
  • We investigated protein levels of the signaling pathway: p35, cyclin-dependent kinase 5, Munc18a, syntaxin 1A and 1B, Munc18-interacting protein 1 and Munc18-interacting protein 2 in Alzheimer's disease cortex and found that this pathway was up-regulated in the Alzheimer's disease parietal and occipital cortex. (eur.nl)
  • Cell cycle-dependent cytotoxicity, G2/M phase arrest, and disruption of p34cdc2/cyclin B1 activity induced by doxorubicin in synchronized P388 cells. (aspetjournals.org)
  • Our results suggest that anthracycline-induced cytotoxicity is cell cycle dependent and is mediated, at least in part, by disturbance of the regulation of p34cdc2/cyclin B1 complex, thus leading to G2/M phase arrest. (aspetjournals.org)
  • 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)
  • DHA-enriched fish oil upregulates cyclin-dependent kinase inhibitor 2A (P16 INK ) expression and downregulates telomerase activity without modulating effects of PPARγ Pro12Ala polymorphism in type 2 diabetic patients: A randomized, double-blind, placebo-controlled clinical trial. (bvsalud.org)
  • The oscillations of the cyclins, namely fluctuations in cyclin gene expression and destruction by the ubiquitin mediated proteasome pathway, induce oscillations in Cdk activity to drive the cell cycle. (wikipedia.org)
  • Dr. Pestell and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 gene deleted. (sciencedaily.com)
  • Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis. (sciencedaily.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)
  • 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)
  • Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (bdbiosciences.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)
  • 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 molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). (medscape.com)
  • The cyclin box is a protein binding domain. (nih.gov)
  • The researchers noticed that cells lacking cyclin D1 produced less of the miRNA-processing protein, Dicer, and therefore had reduced levels of mature miRNA. (sciencedaily.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)
  • This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. (novusbio.com)
  • This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (novusbio.com)
  • 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)
  • Furthermore, we found that levels of phosphorylated MEK1/2 and ERK1/2 were decreased in cyclin I-deficient podocytes and that inhibition of MEK1/2 restored Bcl2 and Bcl-XL protein levels. (jci.org)
  • The expression of Cyclin D1 protein was detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. (fluoridealert.org)
  • In the fluoride-exposed population, the results showed that with the increase in UF content, the expression of miR-4755-5p decreased gradually, while the mRNA transcription and protein expression of Cyclin D1 increased gradually. (fluoridealert.org)
  • Further, the results of miR-4755-5p mimic transfection confirmed that under the action of NaF, miR-4755-5p overexpression reduced Cyclin D1 protein expression within osteoblasts and further inhibited cell proliferation and activation. (fluoridealert.org)
  • The results demonstrate that fluoride exposure induced the downregulation of miR-4755-5p and downregulated miR-4755-5p promoted fluoride-induced osteoblast activation by increasing Cyclin D1 protein expression. (fluoridealert.org)
  • F-box protein specificity for g1 cyclins is dictated by subcellular localization. (umassmed.edu)
  • Components of the canonical wingless (WNT) pathway, including WNT8b, WNT10a, WNT10b, frizzled 1 and 2 and TCF4 were upregulated at the messenger RNA and protein levels following Cyclin A2 depletion. (cnrs.fr)
  • Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. (escholarship.org)
  • Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. (rupress.org)
  • For example, the amino-terminal regions of S and M cyclins contain short destruction-box motifs that target these proteins for proteolysis in mitosis. (wikipedia.org)
  • The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis. (sciencedaily.com)
  • In addition, levels of the prosurvival proteins Bcl-2 and Bcl-XL were reduced in podocytes and neurons from cyclin I-deficient mice, and restoration of Bcl-2 or Bcl-XL expression prevented injury-induced apoptosis. (jci.org)
  • Taken together, these data suggest that a cyclin I-Cdk5 complex forms a critical antiapoptotic factor in terminally differentiated cells that functions via MAPK signaling to modulate levels of the prosurvival proteins Bcl-2 and Bcl-XL. (jci.org)
  • Cyclins are a group of proteins that play a key role in the control and regulation of the cell cycle. (iiarjournals.org)
  • 1992, 1993) that the p34cdc2/cyclin B complex associates with microtubules in the mitotic spindle and premeiotic aster in starfish oocytes, and that microtubule-associated proteins (MAPs) might be responsible for this interaction. (rupress.org)
  • High levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors in multiple tumor types. (aacrjournals.org)
  • Together, these findings elucidate a prosurvival role for cyclin D3-CDK6 in metabolism, in addition to its role in cell-cycle progression, and suggest that high levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors. (aacrjournals.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)
  • 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)
  • Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. (escholarship.org)
  • In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. (sciencedaily.com)
  • A cyclin forms a complex with Cdk, which begins to activate but the complete activation requires phosphorylation, as well. (wikipedia.org)
  • The model is based on a bicyclic phosphorylation-dephosphorylation cascade involving cyclin and cdc2 kinase. (ebi.ac.uk)
  • Cyclin I-Cdk5 showed phosphorylation kinetics similar to those of p35-Cdk5. (jci.org)
  • 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)
  • The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. (sciencedaily.com)
  • 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)
  • Double staining of primate cells with anti-cyclin B and anti-MAP4 antibodies demonstrated these two antigens were colocalized on microtubules and copartitioned following two treatments that altered MAP4 distribution. (rupress.org)
  • The mechanism by which MSLN contributes to these more aggressive behaviors was investigated by using ingenuity pathway analysis, which predicted that increased MSLN could induce cyclin E expression. (cdc.gov)
  • There are several different cyclins that are active in different parts of the cell cycle and that cause the Cdk to phosphorylate different substrates. (wikipedia.org)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (novusbio.com)
  • Cell changes in the cell cycle like the assembly of mitotic spindles and alignment of sister-chromatids along the spindles are induced by M cyclin- Cdk complexes. (wikipedia.org)
  • Expression of cyclins detected immunocytochemically in individual cells in relation to cellular DNA content (cell cycle phase), or in relation to initiation and termination of DNA replication during S-phase, can be measured by flow cytometry. (wikipedia.org)
  • In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1. (sciencedaily.com)
  • They found that patients with the luminal A subtype of breast cancer had increased levels of expression of both cyclin D1 and Dicer. (sciencedaily.com)
  • Like many cyclins, the expression of cyclin C oscillates throughout the cell cycle, with a peak observed during G1 phase. (bdbiosciences.com)
  • Western Blot: Cyclin H Antibody (1B8) [H00000902-M01] - CCNH monoclonal antibody (M01), clone 1B8 Analysis of CCNH expression in HeLa. (novusbio.com)
  • The expression of Cyclin D1 mRNA was detected by qRT-PCR. (fluoridealert.org)
  • The relative miR-4755-5p expression showed a negative correlation with Cyclin D1 expression. (fluoridealert.org)
  • Subsequently, in human osteoblasts treated with sodium fluoride (NaF), the results also showed that NaF caused low expression of miR-4755-5p and increased expression of Cyclin D1 . (fluoridealert.org)
  • Moreover, in breast cancer cells, which express CDK4 instead of CDK6, palbociclib induced cell-cycle arrest instead of apoptosis, further indicating that expression of cyclin D3 and CDK6 in T-ALL cells promotes apoptosis in response to palbociclib. (aacrjournals.org)
  • Additionally, 16 of 18 nonleukemic cancer cell lines exhibiting high expression of cyclin D3 and CDK6 underwent apoptosis in response to palbociclib, and, in melanoma patient-derived xenografts, high cyclin D3 and CDK6 expression was associated with tumor regression after CDK4/6 inhibition. (aacrjournals.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)
  • 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)
  • Functionally, miR-193b induces a G1 cell cycle arrest and cell death in neuroblastoma cell lines by reducing the expression of MYCN , Cyclin D1 and MCL-1 , three important oncogenes in neuroblastoma of which inhibition has shown promising results in preclinical testing. (oncotarget.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)
  • A ) HEK293 cells were transfected with HA-Cdk5, then cotransfected with either myc-p35 or myc-cyclin I. Following an IP to the myc epitope tag on either p35 or cyclin I, in vitro kinase assays were performed using either histone H1 (HH1) or tau as substrates. (jci.org)
  • The mechanisms underlying the prosurvival function of cyclin D3-CDK6 have not been elucidated, prompting Wang and colleagues to search for substrates that may promote cancer cell survival. (aacrjournals.org)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. (nih.gov)
  • This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D1, Cdk4, INK4a and INK4b, pRb etc. (nih.gov)
  • Pope PA, Bhaduri S, Pryciak PM. Regulation of cyclin-substrate docking by a G1 arrest signaling pathway and the Cdk inhibitor Far1. (umassmed.edu)
  • S cyclins bind to Cdk and the complex directly induces DNA replication. (wikipedia.org)
  • In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," says lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology. (sciencedaily.com)
  • However, in T-cell acute lymphoblastic leukemia (T-ALL), which predominately expresses CDK6 and the activating cyclin, cyclin D3, inhibition of CDK6 or cyclin D3 induces apoptosis. (aacrjournals.org)
  • The Cdk- G1/S cyclin complex begins to induce the initial processes of DNA replication, primarily by arresting systems that prevent S phase Cdk activity in G1. (wikipedia.org)
  • For instance, during G1, when one type of cyclin, named D, is synthesized and binds to a CDK, the cell transitions into S phase, as another cyclin, E, peaks and forms a complex with CDK to promote DNA replication. (jove.com)
  • We previously showed that cyclin I does not regulate proliferation, but rather controls survival of podocytes, terminally differentiated epithelial cells that are essential for the structural and functional integrity of kidney glomeruli. (jci.org)
  • cyclin A function was essential for proliferation of hematopoietic and embryonal stem cells. (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)
  • We found that BSW shMSLN cells had decreased cyclin E, and their proliferation rate was reverted to nearly that of untransformed cells. (cdc.gov)
  • Cdk5 activity was reduced in glomeruli and brain lysates from cyclin I-deficient mice, and inhibition of Cdk5 increased in vitro the susceptibility to apoptosis in response to cellular damage. (jci.org)
  • Cyclin D3-CDK6 inhibits the glycolytic enzymes PFK1 and PKM2 to prevent T-ALL cell apoptosis. (aacrjournals.org)
  • 6-phosphofructokinase (PFK1) and pyruvate kinase M2 (PKM2), enzymes that catalyze irreversible, rate-limiting steps in glycolysis, were directly phosphorylated and inhibited by cyclin D3-CDK6, suggesting that cyclin D3-CDK6 may have a unique role in glucose metabolism. (aacrjournals.org)
  • In contrast, Dox treatment was found to induced cyclin B1 accumulation as a result of stimulating its synthesis and inhibiting its degradation. (aspetjournals.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)
  • It promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. It also acts as a transcription repressor of E2F1 target genes. (nih.gov)
  • Downregulation of miR-4755-5p promotes fluoride-induced osteoblast activation via tageting Cyclin D1. (fluoridealert.org)
  • 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)
  • The first of which is the conserved cyclin box, outside of which cyclins are divergent. (wikipedia.org)
  • G1 cyclins do not behave like the other cyclins, in that the concentrations increase gradually (with no oscillation), throughout the cell cycle based on cell growth and the external growth-regulatory signals. (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)
  • 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)
  • 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)
  • Hence deletion of the "floxed" cyclin A2 sequences converts the conditional cyclin A2 allele into a functionally null allele. (immune-source.com)
  • Kaposi sarcoma herpesvirus (KSHV) encodes a D-type cyclin (ORF72) that binds CDK6 and is likely to contribute to KSHV-related cancers. (wikipedia.org)
  • The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. (aacrjournals.org)
  • Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. (sciencedaily.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)
  • 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)
  • 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)
  • Based on a previous study, the aim of this study is to explore the role of miRNA in osteoblast activation of skeletal fluorosis via targeting of Cyclin D1 . (fluoridealert.org)
  • Cyclins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (umassmed.edu)