• Lundberg, A. S. & Weinberg, R. A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. (nature.com)
  • Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. (wuxibiortus.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)
  • 8 , 9 Cell cycle program is regulated by cyclin/cyclin-dependent kinase (CDK) complexes. (jcpjournal.org)
  • During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. (arigobio.cn)
  • The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (affbiotech.cn)
  • Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. (affbiotech.cn)
  • Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. (affbiotech.cn)
  • CDKs show their action by interacting with cyclins and different CDK-cyclin complexes regulate the cell cycle in the G1, S and G2/M phases ( 1 ). (spandidos-publications.com)
  • New anticancer therapy strategies refer to the inhibition of CDK-cyclin complexes as an important target to prevent uncontrolled proliferation and induce apoptosis in cancer cells ( 2 ). (spandidos-publications.com)
  • The N-terminal phosphorylation of RB by p38 bypasses its inactivation by CDKs and prevents proliferation in cancer cells. (nature.com)
  • 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. (wuxibiortus.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. (wuxibiortus.com)
  • NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. (wuxibiortus.com)
  • 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. (wuxibiortus.com)
  • USP37 is activated by phosphorylation and thus triggers G1-S transition. (wuxibiortus.com)
  • 12 The activation of cyclin/CDK complex accelerates cell cycle progression, which are regulated by phosphorylation. (jcpjournal.org)
  • Here we show that cells transactivate the mitotic gene network as they exit the S phase through a CDK1 (cyclin-dependent kinase 1)-directed FOXM1 phosphorylation switch. (elsevierpure.com)
  • Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. (arigobio.cn)
  • Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. (arigobio.cn)
  • In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. (arigobio.cn)
  • HCT 116 colon cancer cells were exposed to purvalanol, which activated ER stress via upregulation of PERK, IRE1α gene expression, eIF-2α phosphorylation and ATF-6 cleavage at early time-points in the HCT 116 colon cancer cells. (spandidos-publications.com)
  • HIV-1 is not restricted in cycling cells and it has been proposed that this is due to phosphorylation of SAMHD1 at T592 in these cells inactivating the enzymatic activity. (biomedcentral.com)
  • Interestingly, no T592 mutants were able to restrict WT HIV-1 in cycling cells, despite not being regulated by phosphorylation and retaining their ability to hydrolyse dNTPs. (biomedcentral.com)
  • However, preventing phosphorylation of SAMHD1 and/or lowering dNTP levels by adding hydroxyurea was not enough to restore restriction in cycling cells. (biomedcentral.com)
  • M3K is activated upon single phosphorylation whereas M2K and MK are both activated upon double phosphorylation[ 2 - 4 ]. (biomedcentral.com)
  • Low PDCD4 level was associated with reduced proliferation but not apoptosis or phosphorylation of endothelial nitric oxide synthase caused by pulsatile shear stress to help maintain the homeostasis of endothelial cells. (plos.org)
  • Fig. 2: p38γ compensates for the loss of CDK1 or CDK2. (nature.com)
  • CDK2/Cyclin A2-H00A-Wuxi Biortus Biosciences Co. Ltd. (wuxibiortus.com)
  • Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (wuxibiortus.com)
  • Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. (affbiotech.cn)
  • Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. (arigobio.cn)
  • Important regulator of cell cycle progression. (affbiotech.cn)
  • Increased levels of polyamines in cells are considered to be involved in cancer progression. (spandidos-publications.com)
  • In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • Although PDCD4 in general suppresses the development and progression of tumors, its specific biological functions differ by cell type [8] . (plos.org)
  • Ample evidence shows that pro-atherosclerotic disturbed flow induces sustained activation of atherogenic genes in endothelial cells to promote their oxidation, inflammation, cell cycle progression and proliferation, whereas pulsatile shear stress tends to maintain endothelial cells in a quiescent and less proliferative state with a low level of oxidation and inflammation [16] , [17] . (plos.org)
  • Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. (nature.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)
  • Feedback loops, both positive and negative are embedded in the Mitogen Activated Protein Kinase (MAPK) cascade. (biomedcentral.com)
  • Signal transduction pathways such as the Mitogen Activated Protein Kinase (MAPK) cascade responds to wide range of external stimuli to trigger growth, cell-division and proliferation[ 1 , 2 ]. (biomedcentral.com)
  • This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. (affbiotech.cn)
  • Purvalanol, a novel cyclin-dependent kinase inhibitor, is referred to as a strong apoptotic inducer which causes cell cycle arrest in various cancer cells such as prostate, breast and colon cancer cell lines. (spandidos-publications.com)
  • Cdk1 (cyclin-dependent kinase 1), also known as p34Cdc2 (cell division control protein kinase 2) depends on cyclin A and B and is triggered by a positive feedback loop at the end of G2 phase, which is the key event that initiates mitotic entry. (arigobio.cn)
  • Destruction of cyclin B during metaphase results in inactivation of Cdk1, allowing mitotic exit and cell division. (arigobio.cn)
  • Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
  • Chromosome association of minichromosome maintenance proteins in Drosophila mitotic cycles. (colorado.edu)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • Activated and released IRE1α acts as an RNase to initiate transcription of XBP1 mRNA and it becomes a transcriptional activator for unfolded protein response (UPR) gene targets, such as BiP and calreticulin ( 10 ). (spandidos-publications.com)
  • The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
  • Application of unidirectional pulsatile shear stress to human umbilical vein endothelial cells (HUVECs) decreased PDCD4 protein but not mRNA level. (plos.org)
  • Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (wuxibiortus.com)
  • The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. (biomedcentral.com)
  • Inhibitory effect of EESR on cancer cell growth and proliferation was determined by water-soluble tetrazolium salt assay. (jcpjournal.org)
  • EESR possessing antioxidant activity efficiently inhibits proliferation of HT29 cells by inducing both cell cycle arrest and apoptosis. (jcpjournal.org)
  • 6 , 7 Therefore, the inhibition of cancer cell proliferation by inducing cell cycle arrest and apoptosis is being an important preventive strategy against cancer. (jcpjournal.org)
  • Natural polyamines, putrescine, spermidine and spermine, play essential roles in the regulation of cell growth and proliferation. (spandidos-publications.com)
  • There is a growing body of evidence which demonstrates that following ACS, microRNAs might inhibit fibroblast proliferation and scarring, as well as harmful apoptosis of cardiomyocytes, and stimulate fibroblast reprogramming into induced cardiac progenitor cells. (archivesofmedicalscience.com)
  • Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. (intechopen.com)
  • Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
  • 13 The expression of CDK inhibitor p21 is upregulated by activated p53, resulting in the suppression of G2/M transition by the inactivation of cyclin/CDK complex. (jcpjournal.org)
  • β-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. (biomedcentral.com)
  • Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient β-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis. (biomedcentral.com)
  • To investigate the mechanism of EESR-mediated cytotoxicity, HT29 cells were treated with various concentrations of EESR and the induction of cell cycle arrest and apoptosis was analyzed by flow cytometry, 4,6-diamidino-2-phenylindole staining, and Western blot analysis. (jcpjournal.org)
  • Cancer cells can grow unusually via limitless number of cell division and can avoid apoptosis. (jcpjournal.org)
  • Although purvalanol-induced cell cycle arrest and apoptotic cell death were demonstrated in prostate ( 5 ), breast ( 6 ) and colon cancer cells ( 7 ), the exact molecular mechanism of purvanol-induced apoptosis has not been elucidated yet. (spandidos-publications.com)
  • Concurrent deletion of cyclin E1 and cyclin-dependent kinase 2 in hepatocytes inhibits DNA replication and liver regeneration in mice. (nature.com)
  • activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. (wuxibiortus.com)
  • During normal DNA replication, the checkpoint kinase ATR (ataxia-telangiectasia and Rad3-related) is activated by ETAA1 to block this switch until the S phase ends. (elsevierpure.com)
  • Cdk1 also contributes to the control of DNA replication. (arigobio.cn)
  • Altogether, we found that the amino acid at residue 592 has a strong effect on tetramer formation and, although this is not a simple "on/off" switch, this does correlate with the ability of SAMHD1 to restrict HIV-1 replication in differentiated cells. (biomedcentral.com)
  • Nonetheless, lowering the affinity of HIV-1 RT for dNTPs, showed that restriction is mediated by dNTP levels and we were able to observe for the first time that SAMHD1 is active and capable of inhibiting HIV-1 replication in cycling cells, if the affinity of RT for dNTPs is reduced. (biomedcentral.com)
  • Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
  • Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
  • inositol-requiring enzyme 1 (IRE1α), PRKR-like ER kinase (PERK) and activating transcription factor-6 (ATF-6). (spandidos-publications.com)
  • When the C-terminal zinc fingers of Tzfp were fused to the transactivation domain of VP16, the chimera activated transcription of a reporter construct containing multiple copies of the tbs. (lookformedical.com)
  • Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. (abcam.cn)
  • The primary microRNA (Pri-miRNA) is produced in the cell nucleus through the transcription of a DNA strand mediated by RNA polymerase II [ 2 ]. (archivesofmedicalscience.com)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • Programmed cell death 4 (PDCD4) is an important tumor suppressor in the development of various human cancers [1] and inhibits translation rather than transcription. (plos.org)
  • We found that CDK1 phosphorylates Ser343 of ERK1c, thereby allowing the binding of phosphorylated ERK1c to a complex that consists of PI4KIIIβ (also known as PI4KB) and the 14-3-3γ dimer (encoded by YWHAB ). (biologists.com)
  • Avoid repeated freeze-thaw cycles. (wuxibiortus.com)
  • Shipped at 4°C. Upon delivery aliquot and store at -20°C. Avoid freeze / thaw cycles. (abcam.cn)
  • In contrast, the same chimera did not activate the reporter gene when an essential nucleotide fifth C was mutated to A at the tbs. (lookformedical.com)
  • Failure to execute these regulatory responses causes cell damage and inflammation or senescence, compromising cell survival and the ability to adapt to energetically demanding conditions. (nature.com)
  • Compellingly however, HIV-1 RT mutants with reduced affinity for dNTPs were significantly restricted by wild-type and T592 mutant SAMHD1 in both cycling U937 cells and Jurkat T-cells. (biomedcentral.com)
  • Abcam is leading the way in addressing this with our range of recombinant monoclonal antibodies and knockout edited cell lines for gold-standard validation. (abcam.cn)
  • Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. (wuxibiortus.com)
  • 10 , 11 The major molecules responsible for G2/M transition are cyclin A /CDK1 and cyclin B/CDK1. (jcpjournal.org)
  • In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
  • However, overexpression of aurora-A in particular cell lines such as NIH3T3 is sufficient to induce growth on soft agar. (lookformedical.com)
  • EESR showed significant antioxidant activity and inhibitory effect on HT29 cell growth in a dose-dependent manner. (jcpjournal.org)
  • We investigated whether atheroprotective unidirectional pulsatile shear stress affects the expression of PDCD4 in endothelial cells. (plos.org)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • However, the action of PDCD4 in endothelial cells is unclear. (plos.org)
  • Vascular endothelial cells, as a monolayer in direct contact with the flowing blood, bear the most of the wall shear stresses and have important homeostatic functions in response to stress [16] . (plos.org)
  • This suggests that the very high affinity of HIV-1 RT for dNTPs prevents HIV-1 restriction by SAMHD1 in cycling cells. (biomedcentral.com)
  • EESR induced cell cycle arrest at G2/M phase in a dose-dependent manner by modulating cyclin B, cyclin-dependent kinase 1 (CDK1), and CDK inhibitor p21 expression. (jcpjournal.org)
  • Whereas damage signals of cells activate p53 via CHK2 to repair damaged DNA, leading to cell cycle arrest. (jcpjournal.org)
  • Purvalanol is a purine-derived CDKI that binds with a high selectivity and competitively to the ATP binding side of CDK1/2 and leads to G2/M cell cycle arrest ( 4 ). (spandidos-publications.com)
  • The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. (jcpjournal.org)
  • The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. (biomedcentral.com)
  • In the present study, our aim was to determine the time-dependent, ER-mediated apoptotic and autophagy induction of purvalanol in HCT 116 colon cancer cells. (spandidos-publications.com)
  • Moreover, we determined that during purvalanol-mediated ER stress, autophagic machinery was also activated prior to apoptotic cell death finalization. (spandidos-publications.com)
  • Olomoucine, roscovitine and purvalanol are examples of CDK inhibitors (CDKIs) designed and investigated for their apoptotic potential on cancer cells ( 3 ). (spandidos-publications.com)
  • Τheir impact on the apoptotic cell death mechanism requires further elucidation. (spandidos-publications.com)
  • Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
  • To distinguish between theories for how SAMHD1 restricts HIV-1 in differentiated but not cycling cells, we analysed the effects of substitutions at T592 on restriction and dNTP levels in both cycling and differentiated cells as well as tetramer stability and enzymatic activity in vitro. (biomedcentral.com)
  • Mitochondrial energetic adaptations encompass a plethora of conserved processes that maintain cell and organismal fitness and survival in the changing environment by adjusting the respiratory capacity of mitochondria. (nature.com)
  • Golgi fragmentation is a highly regulated process that allows division of the Golgi complex between the two daughter cells. (biologists.com)
  • Key regulator of entry into cell division that acts as a tumor suppressor. (abcam.cn)
  • Fifteen micromoles of purvalanol induced a reduction in cell viability by 20 and 35% within 24 and 48 h, respectively. (spandidos-publications.com)
  • The evolutionarily conserved structure of the three layer MAPK cascade consists of the MAPKKK (henceforth referred as M3K), MAPKK (henceforth referred as M2K) and MAPK (henceforth referred as MK) from yeast to human, which processes the incoming signal through a series of covalent modification cycles[ 1 ]. (biomedcentral.com)
  • The CDKN2A/B locus contains genes encoding cell cycle inhibitors, including p16 Ink4a , which have not yet been implicated in the control of hepatic glucose homeostasis. (diabetesjournals.org)
  • We found that a subset of mutants lost their ability to restrict HIV-1 in differentiated cells which generally corresponded with a decrease in triphosphohydrolase activity and/or tetramer stability in vitro. (biomedcentral.com)