• Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (proteopedia.org)
  • Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases. (proteopedia.org)
  • Cyclins and cyclin-dependent kinases (cdks) are evolutionarily conserved proteins that are essential for cell-cycle control in eukaryotes. (bdbiosciences.com)
  • Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
  • In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. (ox.ac.uk)
  • Preeminent among these proteins are the cyclin dependent kinases, which upon binding to cyclins, phosphorylate numerous targets to trigger cell cycle progression. (smadpathway.com)
  • Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. (wuxibiortus.com)
  • Cyclins function as regulators of CDK kinases. (creative-biolabs.com)
  • Serine/Threonine Kinases (STKs), Plant B-type Cyclin-Dependent protein Kinase (CdkB) subfamily, catalytic (c) domain. (umbc.edu)
  • The interactions of cyclins, cyclin-dependent kinases (CDKs), and their inhibitors regulate cell cycle progression. (springeropen.com)
  • Repetitive cell cycles, which are essential to the perpetuation of life, are orchestrated by an underlying biochemical reaction network centered around cyclin-dependent protein kinases (Cdks) and their regulatory subunits (cyclins). (ox.ac.uk)
  • These changes are orchestrated by a small number of master regulators, including the cyclin-dependent kinases (Cdks) and the anaphase-promoting complex/cyclosome (APC/C). Each Cdk or APC/C isoform has a large number of substrates, and the substrates of each isoform are modified in a specific order that leads to sequential substrate activation or inactivation. (biomedcentral.com)
  • The laboratory of Dr. Hasan studies the interplay between anti-apoptotic proteins and cyclin dependent kinases and how this interplay can serve as a potential therapeutic target in Acute Myeloid Leukemia (AML). (actrec.gov.in)
  • Development through mitosis depends upon three major regulatory systems, each involving several serine/threonine kinases, referred to as mitotic kinases. (survivinpathway.com)
  • Right chromosome segregation is closely controlled by mitotic kinases such as cyclin dependent NIMA related kinase 2, Pololike kinase, kinase 1 and Aurora kinases. (survivinpathway.com)
  • Within this review, we summarize the functions that all of the Aurora kinases has in cancer biology and mitosis, and discuss the binding modes of Aurora A kinase inhibitors, the spot elements in the binding sites and the fortunate inhibitor components. (survivinpathway.com)
  • 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)
  • CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
  • 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)
  • CDKs belong to a large family of STKs that are regulated by their cognate cyclins. (umbc.edu)
  • 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)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • Using degron tags for rapid inducible protein removal, we analyse how acute depletion of these proteins affects mitosis . (bvsalud.org)
  • Cells lacking cyclin B can enter mitosis and phosphorylate most mitotic proteins , because of parallel PP2AB55 phosphatase inactivation by Greatwall kinase . (bvsalud.org)
  • During anaphase of mitosis, the proteins that connect these chromatids are destroyed. (visionaryforge.com)
  • The centromere proteins (CENPs), a critical mitosis-related protein complexes, are involved in the kinetochore assembly and chromosome segregation. (ijbs.com)
  • Both proteins may play a role in UC progression and can have a value as prognostic and/or diagnostic markers of UC, as well as targeted therapies. (springeropen.com)
  • Survivin belongs to the family of inhibitors of apoptosis proteins (IAPs) that plays a pivotal role in mitotic progression, apoptosis inhibition, angiogenesis, progression of cancer, and invasion [ 5 ]. (springeropen.com)
  • Progression through the cell cycle is accompanied by dramatic changes in cellular content and behavior, and involves a large number of proteins and processes. (biomedcentral.com)
  • The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.com)
  • The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that regulates progression through the cell cycle by marking key cell division proteins for destruction. (ugent.be)
  • controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. (proteopedia.org)
  • Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (bdbiosciences.com)
  • Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. (eur.nl)
  • Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. (eur.nl)
  • Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells. (eur.nl)
  • The final barrier to mitotic establishment corresponds to nuclear envelope breakdown, which requires a decisive shift in the balance of cyclin-dependent kinase Cdk1 and PP2AB55 activity. (bvsalud.org)
  • Beyond this point, cyclin B /Cdk1 is essential for phosphorylation of a distinct subset of mitotic Cdk1 substrates that are essential to complete cell division . (bvsalud.org)
  • Our results identify how cyclin A , cyclin B and Greatwall kinase coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phosphorylation . (bvsalud.org)
  • Along with Cdk1/cyclin N, members of the Aurora/Ipl1 kinase family are also crucial regulators of mitosis. (smadpathway.com)
  • The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. (wuxibiortus.com)
  • Oscillations of Cdk1/CycB activity between low and high levels during the cycle trigger DNA replication and mitosis in the correct order. (ox.ac.uk)
  • In eukaryotes, the entry into mitosis is regulated by the activation of CDC2/Cyclin B1 complex (M-phase promoting factor, MPF). (biomedcentral.com)
  • The studies on checkpoint control have identified a mechanism by which entry into mitosis is regulated in response to incomplete DNA replication and DNA damage and the identification of a potential target for therapeutic intervention. (actrec.gov.in)
  • In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells. (wikipedia.org)
  • Forms of mitosis (of karyokinesis step) in eukaryotes closed intranuclear pleuromitosis closed extranuclear pleuromitosis closed orthomitosis semiopen pleuromitosis semiopen orthomitosis open orthomitosis In the mitotic metaphase (see below), typically the chromosomes (each containing 2 sister chromatids that developed during replication in the S phase of interphase) align themselves on the metaphase plate. (wikipedia.org)
  • Two mitotic cyclin types, cyclin A and B, exist in higher eukaryotes , but their specialised functions in mitosis are incompletely understood. (bvsalud.org)
  • Multicellular eukaryotes undergo mitosis in order to become an entire organism. (visionaryforge.com)
  • regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (proteopedia.org)
  • NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. (proteopedia.org)
  • Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (proteopedia.org)
  • β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. (ox.ac.uk)
  • Alternatively, in the quantitative model, the gradual rise of Cdk activity from G1 phase to mitosis leads to ordered substrate phosphorylation at sequential thresholds. (crick.ac.uk)
  • DARPP-32 can itself inhibit the following PKA DARPP-32 phosphorylation by cyclin-dependent kinase 5 (Cdk5). (pp1a.com)
  • Exposure of the cells to gemcitabine at G2/M transition abolished the progression of mitosis, caused mitotic arrest and failure to exit mitosis as evidenced by the inhibition of Cyclin B degradation and absence of de-phosphorylation of cdc-2 at Tyr 15 residue. (bmj.com)
  • PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.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)
  • PHOSPHORYLATION of stathmin occurs during CELL CYCLE progression, and stathmin functions as a microtubule-destabilizing protein that promotes MICROTUBULE depolymerization during INTERPHASE and late MITOSIS. (bvsalud.org)
  • Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)
  • It is inhibited by Cyclin-dependent kinase inhibitors (CKI). (biomedcentral.com)
  • Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
  • β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
  • The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. (ox.ac.uk)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (creative-biolabs.com)
  • Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C Cdc20 , a key regulator of chromosome segregation in mitosis. (biomedcentral.com)
  • The activator Cdc20 is then replaced by a second activator, Cdh1, and APC/C Cdh1 promotes complete degradation of M cyclin, followed by polo-like kinase 1, Aurora A, and other substrates, to complete mitosis and cytokinesis and drive progression into G1 [ 1 , 2 ]. (biomedcentral.com)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. (creative-biolabs.com)
  • Recently, we have identified ULTRAVIOLET-B-INSENSITIVE4 (UVI4) as a plant-specific component of the APC/C. Here, we demonstrate that UVI4 uses conserved APC/C interaction motifs to counteract the activity of the CELL CYCLE SWITCH52 A1 (CCS52A1) activator subunit, inhibiting the turnover of the A-type cyclin CYCA2;3. (ugent.be)
  • Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase. (umbc.edu)
  • 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)
  • Here, we study the relative contributions of qualitative and quantitative Cdk control in Saccharomyces cerevisiae All S phase and mitotic cyclins can be replaced by a single mitotic cyclin, albeit at the cost of reduced fitness. (crick.ac.uk)
  • In yeast and Drosophila, Cdh1-dependent APC (Cdh1-APC) activity targets mitotic cyclins from the end of mitosis to the G 1 phase. (elsevierpure.com)
  • However, similarly to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G 1 , resulting in abrogation of G 1 , arrest caused by treatment with rapamycin, an inducer of p27 Kipl . (elsevierpure.com)
  • In yeast and Drosophila, Cdh1-dependent APC (Cdh1-APC) activity targets mitotic cyclins from the end of mitosis to the G1 phase. (elsevierpure.com)
  • However, similarly to yeast and Drosophila, loss of Cdh1 induced unscheduled accumulation of mitotic cyclins in G1, resulting in abrogation of G1, arrest caused by treatment with rapamycin, an inducer of p27Kipl. (elsevierpure.com)
  • A single cyclin can also replace all G1 cyclins to support ordered cell cycle progression, fulfilling key predictions of the quantitative model. (crick.ac.uk)
  • However, single-cyclin cells fail to polarize or grow buds and thus cannot survive. (crick.ac.uk)
  • PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. (ox.ac.uk)
  • This ordering of substrate modification allows a small number of master regulators to carry out their functions over a large time window with high temporal resolution, enabling precise and robust control of the numerous processes underlying cell cycle progression [ 1 , 2 ]. (biomedcentral.com)
  • Group 3 cyclins (G1, G2 and I) may play a role distinct from either cell cycle or transcriptional regulation. (bdbiosciences.com)
  • Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle. (ox.ac.uk)
  • This event is required to promote mitotic progression and favors the activation of a transcriptional program required for mitosis. (ox.ac.uk)
  • 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)
  • These problems start early in mitosis and are alleviated by depletion of isoform 1 of PRC1 (PRC1-1), by gene ablation of its binding partner KIF4, or by abrogation of KIF4 motor activity. (eur.nl)
  • 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)
  • In the present study, we investigated the relationship of gene expression profiles with malignant progression of human glioma. (biomedcentral.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)
  • Two models have been put forward for cyclin-dependent kinase (Cdk) control of the cell cycle. (crick.ac.uk)
  • Our results suggest that budding yeast has become dependent on G1 cyclin specificity to couple cell cycle progression to essential morphogenetic events. (crick.ac.uk)
  • Human cancer cells are usually seen as a changes in the amount or organization of DNA because of mistakes in mitosis, causing chromosome instability and aneuploidy. (survivinpathway.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)
  • embryos were observed (Physique 1C) consisted with the early embryonic lethality associated with a cyclin A-null phenotype. (immune-source.com)
  • The different stages of mitosis all together define the mitotic (M) phase of animal cell cycle-the division of the mother cell into two genetically identical daughter cells. (wikipedia.org)
  • PSMA-expressing cells prematurely degrade cyclin B and exit mitosis due to increased APC activity and incomplete inactivation of APC by the spindle assembly checkpoint. (nih.gov)
  • cyclin A function was essential for proliferation of hematopoietic and embryonal stem cells. (immune-source.com)
  • 1992 In addition cyclin A2 was postulated to play a role in access of cells into mitosis (Swenson et al. (immune-source.com)
  • Cyclin A2f/+ ES cells were then injected into mouse blastocysts and homozygous cyclin A2f/f animals were generated using standard procedures (Geng et al. (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)
  • 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)
  • Two new cells are formed during mitosis, the step in the cell cycle when the newly duplicated DNA is separated. (visionaryforge.com)
  • In mitosis, new cells are produced. (visionaryforge.com)
  • The first round of mitosis results in only two cells. (visionaryforge.com)
  • Both of these cells undergo mitosis, and there are four of them. (visionaryforge.com)
  • The pathways that initiate mitosis are activated by nearby cells without sensing their neighbors. (visionaryforge.com)
  • It is expressed in cancer cells during the G2/M phase of the cell cycle and counteracts apoptosis activation during mitosis by interfering with caspase activity [ 6 ]. (springeropen.com)
  • This group focuses on the cell biology of normal and tumor cells and how these differences can explain tumor progression and possibly identify potential targets for therapeutic intervention. (actrec.gov.in)
  • The objectives of these studies are to provide novel insights into how the cell regulates organelle size and number, how these mechanisms are altered in tumor cells and the subsequent consequences for tumor progression. (actrec.gov.in)
  • During cell-cycle progression, substrates of a single master regulatory enzyme can be modified in a specific order. (biomedcentral.com)
  • To ensure correct cell cycle progression, accurate timing of APC/C activity is important, which is obtained through its association with both activating and inhibitory subunits. (ugent.be)
  • In the qualitative model, cell cycle events are ordered by distinct substrate specificities of successive cyclin waves. (crick.ac.uk)
  • Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (proteopedia.org)
  • CDK2/Cyclin A2-H00A-Wuxi Biortus Biosciences Co. Ltd. (wuxibiortus.com)
  • Immunohistochemical identification of molecular genetic events in the progression of preneoplastic lesions to spindle cell squamous-cell carcinoma enables early detection of lesions with the potential for malignant progression, thus permitting timely intervention 1,2 . (bvsalud.org)
  • Studies suggest that expression of cystatin A is inversely associated with malignant progression of cancer 9 . (bvsalud.org)
  • They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. (umbc.edu)
  • Increasingly numerous results have demonstrated overexpression of CDC2/Cyclin B1 in various tumors however there is still no report of CDC2/Cyclin B1 expression in clinical samples from patients with gliomas. (biomedcentral.com)
  • They are characterized by the cyclin binding motif PPT[A/T]LRE. (umbc.edu)
  • The results demonstrated that JIB extract combined with cisplatin enhanced the inhibition of cell growth, proliferation, and survival through the obstruction of cell cycle progression and AKT/mTOR and MAPK signaling as well as the induction of cell apoptosis. (medsci.org)
  • The laboratory of Dr. Teni also focuses on understanding the regulation of tumor progression by p53 family members and their downstream targets in oral and cervical cancer progression. (actrec.gov.in)
  • Ovarian cancer is frequently sensitive to chemotherapy at diagnosis but rapid development of drug resistance leads to disease progression and ultimately death in the majority of patients. (biomedcentral.com)
  • The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. (creative-biolabs.com)
  • We have also argued that bistability underlies irreversible transitions between low and high Cdk activity states and thereby ensures directionality of cell cycle progression. (ox.ac.uk)
  • The laboratories of Dr. Dalal, Dr. Hasan and Dr. Teni study cell cycle progression and checkpoint control. (actrec.gov.in)
  • More recently, cyclins are being shown to have additional functions not restricted to cell cycle regulation. (bdbiosciences.com)
  • Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. (biomedcentral.com)
  • Appropriate regulation of CDC2 is essential for the entry into mitosis. (biomedcentral.com)
  • however, the mechanisms underlying the regulation of cyclin F are poorly understood. (ox.ac.uk)
  • Conclusion: p63, p16, MIB, Cal A, Cys A are markedly expressed and p16 is strongly suppressed in oral cavity tumors, which suggests that the latter protein may play a role in negative regulation of cell cycle progression. (bvsalud.org)
  • 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)
  • Tissue microarrays (TMAs) including I-IV grade clinical glioma samples was used to determine the prognostic effect of the CDC2/Cyclin B1 expression in gliomas on different grades. (biomedcentral.com)
  • To reveal the roles of CDC2/Cyclin B1 in human malignant gliomas, CDC2 in glioma cell line, it was down-regulated by retrovirus vectors expressing short hairpin RNAs (shRNAs) ex vivo and in vivo. (biomedcentral.com)
  • Tumor specimens were obtained with informed consent from a 37-year-old female patient who underwent initial surgical removal in January 1999 and subsequent recurrent resections of a right temporal tumor July 1999 and February 2001 at the 2nd Affiliated Hospital of Soochow University (Suzhou, China) and did not receive chemotherapy and radiation between these stages of progression. (biomedcentral.com)
  • Thus, these findings provide the first evidence that PSMA has a causal role in the induction of aneuploidy and might play an etiologic role in the progression of prostate cancer. (nih.gov)