• The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. (wikipedia.org)
  • At the cellular level, the process is controlled by different levels of cyclin-dependent kinases (Cdks) and their partner cyclins. (wikipedia.org)
  • b) 4-Hydroxytamoxifen (but not tamoxifen), genistein (but not genistin), daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (biomedcentral.com)
  • Cyclins and cyclin dependent kinases, or CDK. (jove.com)
  • Positive regulators include two protein groups that allow cells to pass through regulatory checkpoints: cyclins and cyclin-dependent kinases (CDKs). (jove.com)
  • Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
  • Cyclins and cyclin-dependent kinases (cdks) are evolutionarily conserved proteins that are essential for cell-cycle control in eukaryotes. (bdbiosciences.com)
  • Among the major cyclin-dependent kinases (Cdks), Cdk1 is most abundantly expressed in IDG-SW3 cells, and its expression is down-regulated during differentiation into osteocytes. (lu.se)
  • 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)
  • 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)
  • 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)
  • 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)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • Activation of the Cyclin B/Cdc2 kinase complex triggers entry into mitosis in all eukaryotic cells. (duke.edu)
  • Cyclin B1 localization changes dramatically during the cell cycle, precipitously transiting from the cytoplasm to the nucleus at the beginning of mitosis. (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)
  • It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. (wikipedia.org)
  • The disappearance of cyclin B at the end of mitosis is regulated spatially in Drosophila cells. (ox.ac.uk)
  • We show that the anaphase-promoting complex/cyclosome (APC/C) specifically interacts with microtubules in embryo extracts, but it is not confined to the spindle in mitosis, suggesting that the spatially regulated disappearance of cyclin B may reflect the spatially regulated activation of the APC/C. (ox.ac.uk)
  • After A is degraded, concentrations of cyclin B peak in M phase and the complex will activate the different stages of mitosis. (jove.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)
  • 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)
  • Its activity is also regulated by phosphorylation. (wikipedia.org)
  • Prior to G1 phase, levels of Cdk4 and Cdk6 increase along with cyclin D. This allows for the partial phosphorylation of Rb, and partial activation of E2F at the beginning of G1 phase, which promotes cyclin E synthesis and increased Cdk2 activity. (wikipedia.org)
  • DARPP-32 can itself inhibit the following PKA DARPP-32 phosphorylation by cyclin-dependent kinase 5 (Cdk5). (pp1a.com)
  • Further studies with pharmacological and genetic approaches revealed that TIGAR regulated the phosphorylation of ATM, a key protein in DDR, through Cdk5. (nature.com)
  • We found Plk1 plays a critical role in maintaining intralysosomal pH by regulating ATP6V1A phosphorylation, and inhibition of Plk1 impaired lysosomal function leading to blockade of autophagic flux. (nature.com)
  • Protein phosphorylation is the most common post-translation modification of proteins and regulates many biological processes. (lu.se)
  • The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. (johnshopkins.edu)
  • Depleting cyclin C in unstressed cells produced an approximately equal number of genes (2400) that were repressed by, or whose transcription required, cyclin C. Consistent with the possibility that cyclin C nuclear release contributes to transcriptional remodeling in response to oxidative stress, we found that 37% cyclin C-dependent genes were downregulated following stress. (researchwithrowan.com)
  • Moreover, 20% of cyclin C- repressed genes were induced in response to stress. (researchwithrowan.com)
  • These findings are consistent with a model that cyclin C relocalization to the cytoplasm, and corresponding inactivation of Cdk8, represents a regulatory mechanism to repress and stimulate transcription of stress-responsive genes. (researchwithrowan.com)
  • Orthologous to several human genes including CCNB1 (cyclin B1). (nih.gov)
  • Treatment with honey stops the tumour cells cycle by regulating some genes (cyclin D1, CDK2, p27Kip. (agenciasinc.es)
  • Taken together, our results demonstrate that the exposure of cells to cadmium chloride resulted in cytotoxicity and cell death due to the enhanced ubiquitination and proteolysis and the consequent inhibition of eIF4E gene expression leading to diminished cellular level of critical genes such as cyclin D1. (cdc.gov)
  • 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)
  • Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the CDK2 gene. (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)
  • We identify an important role for DDX5 in G 1 -S-phase progression where it directly regulates DNA replication factor expression by promoting the recruitment of RNA polymerase II to E2F-regulated gene promoters. (aacrjournals.org)
  • 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)
  • Cyclin-G-associated kinase (GAK) , a PD susceptibility gene identified through genome-wide association studies (GWAS), is a ubiquitous serine/threonine kinase involved in clathrin uncoating (see Drosophila Clathrin heavy chain ), though its PD-related function remains elusive. (sdbonline.org)
  • Furthermore, exposure of cells to Cd resulted in a significant inhibition of expression of the cell cycle and growth regulating gene, cyclin D1. (cdc.gov)
  • Transfection of cells with SiRNA specifically targeting eIF4E gene expression also resulted in a significant inhibition of cyclin D1 gene expression suggesting that the observed inhibition of cyclin D1 gene in the Cd-treated cells is most likely mediated through inhibition of eIF4E gene. (cdc.gov)
  • MEN 4 is caused by an inactivating mutation of the CDKN1B gene, which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. (msdmanuals.com)
  • To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin-dependent kinase complex Bur1/2 as a regulator of telomere length. (johnshopkins.edu)
  • Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.com)
  • p27 regulates G1 /S transition by abrogating the activity of cyclin/CDK complexes. (umass.edu)
  • Nuclear import of Cdk/cyclin complexes: identification of distinct mechanisms for import of Cdk2/cyclin E and Cdc2/cyclin B1. (duke.edu)
  • Consequently, most cyclin-dependent kinase (Cdk)/cyclin complexes are localized to the nucleus when active. (duke.edu)
  • 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)
  • In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. (researchwithrowan.com)
  • 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)
  • A cells cycle is positively regulated promoting progress through the stages via the interaction of two classes of proteins found in the cytoplasm. (jove.com)
  • This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. (wikipedia.org)
  • Cdk2 is capable of binding to many different cyclins, including cyclins A, B, E, and possibly C. Recent studies suggest Cdk2 binds preferentially to cyclins A and E, while Cdk1 prefers cyclins A and B. Cdk2 becomes active when a cyclin protein (either A or E) binds at the active site located between the N and C lobes of the kinase. (wikipedia.org)
  • Due to the location of the active site, partner cyclins interact with both lobes of Cdk2. (wikipedia.org)
  • It is important to note that throughout this activation process, cyclins binding to Cdk2 do not undergo any conformational change. (wikipedia.org)
  • Cyclin-dependent kinase 2 is structured in two lobes. (wikipedia.org)
  • Mutations in either BUR1 cyclin-dependent kinase or the associated BUR2 cyclin resulted in short telomeres. (johnshopkins.edu)
  • In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively stressed Mus musculus embryonic fibroblasts. (researchwithrowan.com)
  • By acting as a ligand-dependent transcription factor of the glucocorticoid receptor (GR) mediates the action of glucocorticoids and regulates many physiological processes. (pp1a.com)
  • p27(Kip1) is a cyclin-dependent kinase inhibitor. (biomedcentral.com)
  • The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)
  • Enables cyclin-dependent protein serine/threonine kinase regulator activity. (nih.gov)
  • The mechanism of OGF-OGFr action on DNA synthesis was related to the cyclin-dependent kinase inhibitory pathway because knockdown of p16 or p21 in OVCAR-3 cells, and p21 in SKOV-3 cells, eliminated OGF's inhibitory effect on growth. (nih.gov)
  • 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)
  • Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. (bvsalud.org)
  • It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18. (bvsalud.org)
  • [ 13 ] In one study, arecoline was found to elevate the mRNA and protein expression of cystatin C, a nonglycosylated basic protein consistently up-regulated in a variety of fibrotic diseases, in a dose-dependent manner in persons with oral submucous fibrosis. (medscape.com)
  • Oxidative stress pathways regulate redox balance by Nrf2 and other ways. (springer.com)
  • [ 7 ] Parafibromin can negatively regulate cyclin D1 and may be responsible at least in part for this. (medscape.com)
  • We have followed the behaviour of a cyclin B-green fluorescent protein (GFP) fusion protein in living Drosophila embryos in order to study how the localization and destruction of cyclin B is regulated in space and time. (ox.ac.uk)
  • These findings suggest that the inactivation of cyclin B is regulated spatially in Drosophila cells. (ox.ac.uk)
  • 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)
  • In addition, CPT compromised two- cell cysts differentiation by decreasing the expression of Bam and inducing cell arrest at G1/ S phase via cyclin A , eventually resulting in two- cell accumulation. (bvsalud.org)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • Keratin 19 interacts with GSK3beta to regulate its nuclear accumulation and degradation of cyclin D3. (addgene.org)
  • Scholars@Duke publication: 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)
  • GSK-3 has been shown to regulate cyclin D1 proteolysis and subcellular localization (5). (cellsignal.com)
  • This report addresses the question of whether various nutritional and chemopreventive anti-cancer agents up-regulate the expression of p27 in preneoplastic and neoplastic cells. (biomedcentral.com)
  • Experimental evidence presented in the first half of this report shows that these agents fairly faithfully up-regulate expression of p27 in mouse epidermal (JB6) and human breast cancer (MCF7, MDA-MB-321, and AU565) cells. (biomedcentral.com)
  • Based on these findings, we conclude that various nutritional and chemopreventive anti-cancer agents up-regulate expression of p27 in (pre)neoplastic cells. (biomedcentral.com)
  • Preliminary studies using in vivo model of MNU-induced rat mammary cancer and in vitro model of cultured cells had suggested - but not proved - that various nutritional and chemopreventive anti-cancer agents, including moderate dietary restriction, up-regulated the expression of p27 (Fig. 1a ). (biomedcentral.com)
  • 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)
  • The group also examined cells lacking Dicer, and noted many similarities between Dicer-lacking and cyclin D1-lacking cells, in addition to failure of miRNA processing, suggesting a deeper connection between these two processes. (sciencedaily.com)
  • To consistently produce healthy cells, the cell cycle-the process that generates daughter cells-must be precisely regulated. (jove.com)
  • Understanding how DNA replication is regulated in human cells can provide insight into cancer development and may reveal vulnerabilities that can be exploited therapeutically. (aacrjournals.org)
  • Cyclin A degradation employs preferentially used lysines and a cyclin box function other than Cdk1 binding. (nih.gov)
  • Use of the triple-negative TMX2-28 breast cancer cell line to address the role of SKP2 in cell cycle progression confirmed that SKP2 contributes to a more rapid cell cycle progression and may regulates pSer10p27 levels. (umass.edu)
  • The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis. (sciencedaily.com)
  • This regulation did not function through the known role of BUR1 in regulating histone modification as bur1∆ set2∆ and bur2∆ set2∆ double mutants rescued cell growth but did not rescue the telomere shortening effects. (johnshopkins.edu)
  • When up-regulated, p27 inhibits G1-to-S phase transition of the cell cycle. (biomedcentral.com)
  • Some proto-oncogenes work to regulate cell death. (cancerquest.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)
  • 15. These proteins are involved in regulating the timing of the cell cycle. (classtools.net)
  • The decrease in the number and size of glutamatergic neuronal population affects all cortical layers but is restricted to the frontal and parietal cortices without any change in the occipital cortex, indicating that Fgf2 is necessary to regulate cell number and size in the anterior cerebral cortex. (jneurosci.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)
  • Cyclins can be categorized as G 1 , G 1 /S, S, or M cyclins based on the cell cycle phase or transition they are most involved in. (jove.com)
  • Generally, levels of a given cyclin are low during most of the cell cycle but abruptly increase at the checkpoint they most contribute to (G 1 cyclins are an exception, as they are required throughout the cell cycle). (jove.com)
  • More recently, cyclins are being shown to have additional functions not restricted to cell cycle regulation. (bdbiosciences.com)
  • Group 3 cyclins (G1, G2 and I) may play a role distinct from either cell cycle or transcriptional regulation. (bdbiosciences.com)
  • Like many cyclins, the expression of cyclin C oscillates throughout the cell cycle, with a peak observed during G1 phase. (bdbiosciences.com)
  • It helps regulate the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion. (medlineplus.gov)
  • Because p27 plays such a key role in controlling cell division, its activity is tightly regulated. (medlineplus.gov)
  • All of these mutations reduce the amount of functional p27 that is available in the nucleus to regulate the cell cycle. (medlineplus.gov)
  • The protein is involved in cellular growth and development and has an important role in regulating the cell cycle. (msdmanuals.com)
  • Amino acid deficiencies also up-regulate the expression of p27 using some components of this pathway. (biomedcentral.com)
  • Met(5)]-enkephalin) and the OGF receptor (OGFr) form an endogenous growth-regulating pathway in homeostasis and neoplasia. (nih.gov)
  • The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. (jneurosci.org)
  • Instead, CPT induced ectopic expression of a differentiation factor, bag of marbles (Bam), and regulated the expression of cyclin A , which contributed to GSC loss. (bvsalud.org)
  • Up-regulation appears to be specific to p27 because expression of cyclin D1, E, and A, and p21Cip1/Waf1 was not modulated by these agents. (biomedcentral.com)
  • c) Expression of p27 could also be up-regulated via RPTKs followed by MAPKs - MEK, ERK and p38MAPK - and probably MNK. (biomedcentral.com)
  • Finally, (d) global hypomethylation of 5'-m 7 G cap of mRNAs could also up-regulate expression of p27. (biomedcentral.com)
  • Tissue specificity of cyclin B expression in D. melanogaster]. (nih.gov)
  • 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)
  • These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. (researchwithrowan.com)
  • In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. (sciencedaily.com)
  • Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (intechopen.com)
  • Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. (researchwithrowan.com)
  • The endogenous cyclin B protein appears to behave in a similar manner. (ox.ac.uk)
  • Glycogen synthase kinase-3 (GSK-3) was initially identified as an enzyme that regulates glycogen synthesis in response to insulin (1). (cellsignal.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 researchers also measured, in each well, the level of two proteins found to be pluripotency markers, OCT4 and cyclin B1. (eurekalert.org)
  • 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)
  • The parathyroids are small endocrine glands in the neck that regulate the circulating calcium level by producing and secreting parathyroid hormone (PTH), which acts to maintain homeostasis by regulating bone mineral turnover, calcium reabsorption by the kidneys, and dietary calcium absorption from the gut. (medscape.com)
  • Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. (sciencedaily.com)
  • In most cases, when a cyclin is degraded, the CDK is inactivated, signaling the end of a particular phase. (jove.com)
  • 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)
  • In conclusion, this study demonstrated that Plk1 plays a pathogenic role in renal tubulointerstitial fibrosis by regulating autophagy/lysosome axis. (nature.com)