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Cyclin ECyclin D1Cyclin ACyclin BCyclin B1Cyclin D3Cyclin D2Cyclin A1Cyclin DCyclin A2CyclinsCyclin-Dependent Kinase 2Cyclin-Dependent KinasesCyclin G1Cyclin GCDC2-CDC28 KinasesCell CycleCyclin CG1 PhaseCyclin-Dependent Kinase 4Cyclin B2Cell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p27S PhaseCyclin TRetinoblastoma ProteinCyclin G2Cyclin HOncogene ProteinsCDC2 Protein KinaseProtein-Serine-Threonine KinasesCyclin-Dependent Kinase Inhibitor p21PhosphorylationF-Box ProteinsMitosisCell Line, TumorCell ProliferationE2F Transcription FactorsTumor Suppressor ProteinsCell DivisionGene Expression Regulation, NeoplasticCyclin ICyclin-Dependent Kinase 6RNA, MessengerMicrotubule-Associated ProteinsGenes, bcl-1Signal TransductionProto-Oncogene ProteinsE2F1 Transcription FactorTranscription FactorsBlotting, WesternNuclear ProteinsCell LineTumor Cells, CulturedDown-RegulationTumor Suppressor Protein p53ApoptosisG2 PhaseImmunohistochemistryMolecular Sequence DataDNA-Binding ProteinsRetinoblastoma-Binding Protein 1Transcription Factor DP1cdc25 PhosphatasesGene Expression RegulationMutationProto-Oncogene Proteins c-mycProliferating Cell Nuclear AntigenTransfectionG0 PhaseCyclin-Dependent Kinase Inhibitor p16Protein BindingPromoter Regions, GeneticCell NucleusBreast NeoplasmsTranscription, GeneticCells, CulturedRNA, Small InterferingCell Transformation, NeoplasticReverse Transcriptase Polymerase Chain ReactionRetinoblastoma-Like Protein p1073T3 CellsS-Phase Kinase-Associated ProteinsBase SequenceFibroblastsProtamine KinaseAmino Acid SequenceHeLa CellsDNA ReplicationUbiquitin-Protein LigasesModels, BiologicalProtein KinasesSKP Cullin F-Box Protein LigasesCentrosomeUp-RegulationEnzyme ActivationEnzyme InhibitorsGene ExpressionCarrier ProteinsXenopus Proteins
KinasesPhosphorylationProteinsInhibitorsPathwayKinase inhibitor 2AOverexpressionCDK2ProgressionDependentCDK4MRNASubunitsDifferentiationApoptosisTranslocationRetinoblastomaMitoticInhibitionTranscriptionalExpressionRegulatoryAbsenceMalignantNuclearTumorsCDK6Cdk5CellsGrowthCancerMajorDevelopmentStatusAnalysis
Kinases10
Phosphorylation16
  • 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)
  • After binding the Cyclin in the PSTAIRE helix, the protein changes its conformational structure to expose the phosphorylation motif. (wikipedia.org)
  • Endogenous regulation of the cell cycle depends on phosphorylation and dephosphorylation of the cyclin- cyclin-dependent kinase (CDK)-cyclin-dependent kinase inhibitor (CDKI) pathway. (jcancer.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)
  • As a result, it negatively regulates cyclin-D-dependent phosphorylation of the retinoblastoma (pRb) gene product, thus blocking cell-cycle progression from G 1 -to S-phase ( 2 - 4 ). (iiarjournals.org)
  • Studies with Mcl-1 phosphorylation mutants show that cyclin E/Cdk2-dependent phosphorylation of Mcl-1 residues on its PEST domain resulted in increased Mcl-1 stability (Thr92, and Thr163) and Bim binding (Ser64). (oncotarget.com)
  • These enzymes are controlled by transient associations with cyclin regulatory subunits, binding of inhibitory polypeptides and reversible phosphorylation reactions. (unibas.ch)
  • Subsequently, a different set of CDK/cyclin complexes triggers the phosphorylation of numerous proteins to promote the profound structural reorganizations that accompany the entry of cells into mitosis. (unibas.ch)
  • v-Jun overrides the mitogen dependence of S-phase entry by deregulating retinoblastoma protein phosphorylation and E2F-pocket protein interactions as a consequence of enhanced cyclin E-cdk2 catalytic activity. (ox.ac.uk)
  • D-cyclin-cdk activity is required for Rb phosphorylation in v-Jun-transformed cells, since ectopic expression of the cdk4- and cdk6-specific inhibitor p16(INK4A) inhibits both DNA synthesis and cell proliferation. (ox.ac.uk)
  • In particular, hormonal activation of a conditional v-Jun-estrogen receptor fusion protein in quiescent, growth factor-deprived cells stimulates cyclin E-cdk2 activity and triggers Rb phosphorylation and DNA synthesis. (ox.ac.uk)
  • One of these events is protein phosphorylation, which when altered may result in system-wide disruption and deregulation of signal transduction. (ubigene.us)
  • It is well understood that changes in phosphorylation signaling can be due to deregulation of kinase and phosphatase function, usually detected through altered gene expression. (ubigene.us)
  • Disruptions of phosphorylation sites are associated with cancer, for instance, mutations of T286 in cyclin D1 (CCND1). (ubigene.us)
  • Phosphorylation of T286 by GSK3B in the wild type form of cyclin D1 initiates its nuclear export and subsequent degradation in the cytoplasm, while the loss of phosphorylation is causatively implicated in nuclear accumulation of cyclin D1 in esophageal cancer and generally increased oncogenic potential. (ubigene.us)
  • A mechanism of signal transduction deregulation in cancer is mediated by either removal or creation of phosphorylation sites thereby causing either a loss or a gain of phosphorylation function, depending on the role of the phosphorylated residue. (ubigene.us)
Proteins3
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)
  • Here, we show that cyclin E/Cdk2 phosphorylates and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). (oncotarget.com)
  • Collectively, our findings identify a novel mechanism of cyclin E-mediated Mcl-1 regulation that provides a rationale for clinical use of Bcl-2 family and Cdk inhibitors for Mcl-1-dependent tumors. (oncotarget.com)
  • Controlling the deregulation with cell cycle inhibitors has shown to be beneficial for survival. (ucc.ie)
  • Deregulation of cell cycle and transcriptional control are general features of tumor cells, highlighting the potential for the use of CDK7 inhibitors as novel cancer therapeutics. (imperial.ac.uk)
Pathway7
  • Pope PA, Bhaduri S, Pryciak PM. Regulation of cyclin-substrate docking by a G1 arrest signaling pathway and the Cdk inhibitor Far1. (umassmed.edu)
  • Defects of the retinoblastoma protein (pRb)/cyclin-D1/p16 pathway have been shown to play a critical role in the development of human malignancies. (iiarjournals.org)
  • Activating the HH pathway affects expression of Ptch1 cyclin D1 cyclin E insulin-like growth factor 2 (IGF2) insulin-like growth factor binding protein 6 (IGFBP6) GILZ and other species (2-5). (acancerjourney.info)
  • HH pathway deregulation occurs in many tumors including lung (6) breast (7) and pancreatic (8) cancers. (acancerjourney.info)
  • The HH pathway regulates growth of small cell lung Protopanaxdiol IC50 cancer (SCLC) and non-small cell lung tumor (NSCLC) (6 15 HH pathway people are abundantly indicated within the premalignant and malignant lungs of cyclin E-expressing transgenic mice (16). (acancerjourney.info)
  • Cyclin E-driven transgenic and transplantable murine lung tumor versions that spontaneously triggered the HH pathway had been available for research as was a combined human being normal-malignant lung cells array Protopanaxdiol IC50 with an connected clinical data source. (acancerjourney.info)
  • Oxidative stress and deregulations in base excision repair pathway as contributors to gallbladder anomalies and carcinoma - a study involving North-East Indian population. (cdc.gov)
Kinase inhibitor 2A1
  • In particular, the p16/cyclin-dependent kinase inhibitor 2A (CDKN2A) gene located on chromosomal region 9p21 frequently is altered in several types of cancer. (iiarjournals.org)
Overexpression6
  • The genetic characteristic of MCL is definitely the capital t (11;14)(q13;q32) mutation, resulting in the overexpression of cyclin M1. (mdm2-inhibitors.com)
  • Overexpression of cyclin D1 and cyclin E in 1,2-dimethylhydrazine dihydrochloride-induced rat colon carcinogenesis. (ewha.ac.kr)
  • Our results indicate that the overexpression of cyclin D1 and cyclin E may play an important role during the multistage process of rat colon carcinogenesis, at a relatively early stage, and may disturb cell-cycle control in benign adenomas, and thereafter, participate in tumor progression. (ewha.ac.kr)
  • The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1). (lookformedical.com)
  • The translocation t(11;14)(q13;q32) is considered the precipitating oncogenic event that induces cell cycle deregulation in mantle cell lymphoma due to overexpression of cyclin D1 . (wikidoc.org)
  • This translocation juxtaposes the CCDN1 gene encoding cyclin D1 to the immunoglobulin heavy chain (IgH) leading to its overexpression. (wikidoc.org)
CDK25
  • Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (oncotarget.com)
  • Cyclin E levels were elevated and there was increased association of cyclin E/Cdk2 with Mcl-1 in ABT-737-resistant compared to parental cells. (oncotarget.com)
  • We show that v-Jun enables cells to express cyclin A and cyclin A-cdk2 kinase activity in the absence of growth factors and that deregulation of cdk2 is required for S-phase entry. (ox.ac.uk)
  • Despite this, v-Jun does not stimulate D-cyclin-cdk activity but does induce a marked deregulation of cyclin E-cdk2. (ox.ac.uk)
  • This is the first report, however, that cyclin E-cdk2, rather than D-cyclin-cdk, is likely to be the critical Rb kinase target of v-Jun. (ox.ac.uk)
Progression2
  • Cyclin-dependent kinase (CDK) 10, is reported to play an essential role in the progression from the G2 to M phase of the cell cycle. (jcancer.org)
  • Deregulation of cell cycle progression is considered to be critical for carcinogenesis ( 9 ). (jcancer.org)
Dependent6
  • The protein encoded by this gene is a member of the cyclin-dependent kinase, (CDK) family, which includes CDK4. (wikipedia.org)
  • 3 We previously described that deregulation of cyclin-dependent kinase 5 (Cdk5) activity induced by mutant huntingtin increases the susceptibility of striatal neurons to dopamine via D1 receptor activation. (bmj.com)
  • 4Paoletti P, Vila I, Rifé M, Lizcano JM, Alberch J, Ginés S. Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin dependent kinase 5. (bmj.com)
  • Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronal apoptosis. (bmj.com)
  • Cyclin E knock-down restored ABT-737 sensitivity to acquired and inherently resistant Mcl-1-dependent tumor cells. (oncotarget.com)
  • Purpose: CDK-activation kinase (CAK) is required for the regulation of the cell-cycle and is a trimeric complex consisting of Cyclin Dependent Kinase 7 (CDK7), Cyclin H and the accessory protein, MAT1. (imperial.ac.uk)
CDK41
MRNA3
  • Mechanistically, p100 inhibited Cyclin D1 protein translation by activating the transcription of LARP7 and its hosted miR-302d, which could directly bind to 3′-UTR of cyclin d1 mRNA and inhibited its protein translation. (oncotarget.com)
  • Cyclin E depletion in various human tumor cell-lines and cyclin E -/- mouse embryo fibroblasts showed decreased levels of Mcl-1 protein, with no change in Mcl-1 mRNA levels. (oncotarget.com)
  • Overall, cyclin D1, cyclin E and PCNA expression was significantly increased at both the mRNA and protein levels in normal colonic mucosa, adenomas and adenocarcinomas, but there was no significant difference in the degree of expression of these genes in adenomas and adenocarcinomas. (ewha.ac.kr)
Subunits1
  • Deletions of multiple GID subunits compromise cell proliferation, and this defect is accompanied by deregulation of critical cell cycle markers such as the retinoblastoma (Rb) tumor suppressor, phospho-Histone H3 and Cyclin A. We identify the negative regulator of pro-proliferative genes Hbp1 as a bonafide GID/CTLH proteolytic substrate. (elifesciences.org)
Differentiation3
  • Runx2, p53, and pRB status as diagnostic parameters for deregulation of osteoblast growth and differentiation in a new pre-chemotherapeutic osteosarcoma cell line (OS1). (umassmed.edu)
  • At present, much research is focused on elucidating the links between CDK/cyclin complexes and signal transduction pathways controlling cell growth, differentiation and death. (unibas.ch)
  • p18INK4C can function as a tumor suppressor gene in Hodgkins lymphoma and its inactivation may contribute to the cell cycle deregulation and defective terminal differentiation characteristic of the Reed-Sternberg cells (2). (rockland.com)
Apoptosis1
  • These paclitaxel resistant ovarian cells demonstrate: (1) Increased IC 50 for paclitaxel and docetaxel (10 to 75-fold) and cross-resistance to anthracyclines (2) Reduced cell apoptosis in the presence of paclitaxel (3) Gene depletion involving mitotic regulators BUB1 mitotic checkpoint serine/threonine kinase, cyclin BI (CCNB1), centromere protein E (CENPE), and centromere protein F (CENPF), and (4) Functional data validating gene depletion among mitotic regulators. (biomedcentral.com)
Translocation1
  • Many of the sufferers had been Compact disc5+ and/or CD43+ and indicated cyclin M1 or showed cyclin M1 translocation by FISH (supplemental Table 1A). (mdm2-inhibitors.com)
Retinoblastoma1
Mitotic1
  • Dephosphorylation of Rb and destruction of cyclin A nevertheless occur normally at mitosis, indicating that v-Jun enables cells to rephosphorylate Rb and reaccumulate cyclin A without exogenous mitogenic stimulation each time the mitotic "clock" is reset. (ox.ac.uk)
Inhibition1
  • We demonstrated that mHtt-induced Cdk5 activation is involved in the deregulation of the Drp1 GTPase activity since its inhibition prevents the aberrant activation of this fission protein. (bmj.com)
Transcriptional1
Expression4
  • To investigate the expression pattern of G1 cyclins in 1,2- dimethyl-hydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis, we studied the expression of cyclin D1 and cyclin E by quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and immunohistochemistry (IHC). (ewha.ac.kr)
  • Cyclin D1 expression was detected in 56.3% of the adenomas and in 61.5% of the adenocarcinomas examined, whereas cyclin E expression was detected in 87.5% of the adenomas and in 92.3% of the adenocarcinomas. (ewha.ac.kr)
  • Conclusions: Expression of components of the CAK complex, CDK7, MAT1 and Cyclin H are elevated in breast cancer and correlates with ER. (imperial.ac.uk)
  • To our knowledge, this is the first report to demonstrate the co-over expression of β-catenin and cyclin D1 in case with MCST and concurrent endometrial carcinoma, which may provide new insights to the tumor biology. (austinpublishinggroup.com)
Regulatory1
  • 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)
Absence2
Malignant1
  • Deregulation of normal cell cycle control is essential for malignant transformation. (pitt.edu)
Nuclear1
  • Immunohistochemical staining revealed exclusive nuclear staining of the neoplastic cells for cyclin D1, cyclin E and PCNA. (ewha.ac.kr)
Tumors1
  • Deregulation of G1 cyclins has been reported in several human and rodent tumors including colon cancer. (ewha.ac.kr)
CDK61
Cdk51
  • CDK5 represents an attractive pharmacological target as its deregulation is implicated in various neurodegenerative diseases such as Alzheimer's, Parkinson's, and Niemann-Pick type C diseases, ischemia, and amyotrophic lateral sclerosis. (rcsb.org)
Cells1
Growth2
  • Here we report another MCST case with a solid growth pattern, distinct immunophenotypes including β-catenin and cyclin D1 (a known β-catenin regulated oncogene), and a coexisting endometrial carcinoma. (austinpublishinggroup.com)
  • Here we report another MCST case with a pure solid growth pattern grossly and microscopically, and with a distinct immunophenotypes including cyclin D1 (diffusely positive) and c-Myc (completely negative). (austinpublishinggroup.com)
Cancer1
  • Cell cycle deregulation is regularly seen in pancreatic cancer. (ucc.ie)
Major1
  • This graph shows the total number of publications written about "Cyclins" by people in this website by year, and whether "Cyclins" was a major or minor topic of these publications. (umassmed.edu)
Development1
  • Ishidate T, Elewa A, Kim S, Mello CC, Shirayama M. Divide and differentiate: CDK/Cyclins and the art of development. (umassmed.edu)
Status1
  • SOX11 , a SOX family transcription factor , has recently been identified as an important molecular feature of MCL regardless of cyclin D1 status. (wikidoc.org)
Analysis1
  • Related to cyclin M1Cpositive MCL individuals, the median age at the time of analysis was 60 years (range, 51-65) with male predominance (5 of 7 individuals), and also showed a related immunophenotype, with appearance of B-cell guns and CD5. (mdm2-inhibitors.com)