• In this model, the senescence-sensitive promoter from the cyclin-dependent kinase inhibitor 2A ( Cdkn2a ) gene, also known as p16 INK4a , drives expression of 3MR, a fusion protein that is composed of luciferase and red fluorescent protein (RFP) reporters and herpes simplex virus-1 thymidine kinase, which converts ganciclovir (GCV) into an apoptosis inducer. (jax.org)
  • Cyclins are a group of proteins that play a key role in the control and regulation of the cell cycle. (iiarjournals.org)
  • 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)
  • Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
  • This process is carried out by the human spliceosome machinery, in which over 300 proteins sequentially assemble with uridine-rich small nuclear RNA molecules (U snRNAs) to form distinct small nuclear ribonucleoprotein complexes (snRNPs). (biomedcentral.com)
  • Proteins of the TCF subfamily form a ternary complex by binding to the the serum response factor and the serum reponse element in the promoter of the c-fos proto-oncogene. (nih.gov)
  • This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS. (lookformedical.com)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Serine/Threonine Kinases (STKs), Cyclin-dependent protein kinase 2 (CDK2) and CDK3 subfamily, catalytic (c) domain. (umbc.edu)
  • The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. (umbc.edu)
  • CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. (umbc.edu)
  • The CDK2/cyclin A complex plays a role in regulating DNA replication. (umbc.edu)
  • Cyclin-dependent kinase 2 (CDK2) is a key mediator for EGF-induced cell transformation mediated through the ELK4/c-Fos signaling pathway. (nih.gov)
  • Similarly, depletion in the STRIPAK component STRIP1 affects activation of GCKIII kinases and cell cycle disruption through elevated expression of cyclin dependent kinase inhibitors p21 and p27, enhanced levels of which lead to a protective effect from therapeutic treatments and increased proliferation. (lu.se)
  • Cdk5 is a proline-directed serine/threonine kinase, which was first identified as a CDK family member due to its similar structure to CDC2/CDK1 in humans, a protein that plays a crucial role in the regulation of the cell cycle. (wikipedia.org)
  • Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3. (umbc.edu)
  • We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. (nih.gov)
  • Cdk5 is named after its structural similarity to members of the serine/threonine cyclin-dependent kinase family. (frontiersin.org)
  • Cyclin-dependent kinase 5 is a protein, and more specifically an enzyme, that is encoded by the Cdk5 gene. (wikipedia.org)
  • Even though Cdk5 has a similar structure to other cyclin-dependent kinases, its activators are highly specific (CDK5R1 and CDK5R2). (wikipedia.org)
  • The Cdk5 kinase has an original design as well. (wikipedia.org)
  • Cdk5 belongs to the eukaryotic protein kinases (ePKs). (wikipedia.org)
  • Recently Cdk5 has emerged as an essential kinase in sensory pathways. (wikipedia.org)
  • Unlike other cyclin-dependent kinases, CDK5 does not also require phosphorylation on the T loop. (wikipedia.org)
  • In order to perform, Cdk5 needs to be activated by p35 (these 3 amino acids, Asp-259, Asn-266, and Ser-270, are involved in the formation of hydrogen bonds with Cdk5) or p39 (the isoform of p35), which are two of its neuron-specific regulatory subunits. (wikipedia.org)
  • Here, we enlarge the diversity of chemical decorations, present the synthesis and, The pathological characteristics of Alzheimer's Disease (AD) have been linked to the activity of three particular kinases-Glycogen Synthase Kinase 3β (GSK3β), Cyclin-Dependent Kinase 5 (CDK5) and Extracellular-signal Regulated Kinase 2 (ERK2). (cynioch.pl)
  • 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)
  • 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 I-Cdk5 preferentially phosphorylates tau. (jci.org)
  • 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)
  • In contrast, cyclin I-Cdk5 preferentially phosphorylated tau (lane 6) rather than histone H1 (lane 2). (jci.org)
  • No kinase activity was detected in the presence of a kinase-inactive dominant negative Cdk5 mutant (HA-D145N-Cdk5, lane 3, 7) or in the absence of either Cdk5 (lanes 1, 5) or p35/cyclin I (lanes 4, 8). (jci.org)
  • B ) To compare the kinase kinetics by which cyclin I-Cdk5 phosphorylates tau in comparison with p35-Cdk5, a time-course experiment was performed in HEK293 cells cotransfected with myc-p35 and HA-Cdk5 or myc-cyclin I and HA-Cdk5. (jci.org)
  • Cyclin I-Cdk5 showed phosphorylation kinetics similar to those of p35-Cdk5. (jci.org)
  • GSK3β and Cdk5 are the two kinases in the center of research on Alzheimer's disease (AD), involved in the pathological symptoms of AD, Aβ plaque formation, tau hyperphosphorylation and neurodegeneration. (frontiersin.org)
  • So far, both kinases have mostly been examined in isolation, leading to a schism of the research field into defenders of the GSK3β-versus the Cdk5 hypotheses of AD. (frontiersin.org)
  • Inhibition of Cdk5 by olomoucine enhanced phosphorylation of kinesin, suggesting that the effect was mediated by negative regulation of other kinases. (frontiersin.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)
  • Although we did not identify any highly Clb2-specific substrates, we found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1, enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets. (nature.com)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. (umbc.edu)
  • Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (bdbiosciences.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)
  • 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)
  • Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.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 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)
  • 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)
  • The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. (johnshopkins.edu)
  • Concurrent deletion of cyclin E1 and cyclin-dependent kinase 2 in hepatocytes inhibits DNA replication and liver regeneration in mice. (nature.com)
  • Meriolin 3 potently inhibits tumor growth in two mouse xenograft cancer models, namely, Ewing's sarcoma and LS174T colorectal carcinoma. (rcsb.org)
  • GR-induced dormancy is dependent on a single GR-target gene, CDKN1C, regulated through chromatin looping of a GR-occupied upstream distal enhancer in a SWI/SNF-dependent fashion. (nih.gov)
  • The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.com)
  • Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 and polycomb repressive complex 2. (lookformedical.com)
  • We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
  • Kinases are enzymes that catalyze reactions of phosphorylation. (wikipedia.org)
  • Figure 3: Clb5-specific substrate phosphorylation occurs in vivo . (nature.com)
  • TGF-β1 acts predominantly through phosphorylation of the C-terminal MH2 domains of SMAD2 and SMAD3 via activin receptor-like kinase 5 (ALK5), of which activity is located at the C-terminal part of TGFBR1. (springer.com)
  • Upon phosphorylation, R-SMADs recruit the co-SMAD SMAD-4 to form protein complexes that translocate into the nucleus and exhibit transcriptional activity. (springer.com)
  • Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. (rcsb.org)
  • Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)
  • While the LAP peptides confer latency, LTBP is needed to release active TGF-β1 ligand from the L-TGF-β1 complex upon appropriate stimuli [ 4 ]. (springer.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)
  • 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)
  • This gene is a member of the Ets family of transcription factors and of the ternary complex factor (TCF) subfamily. (nih.gov)
  • The protein encoded by this gene is phosphorylated by the kinases, MAPK1 and MAPK8. (nih.gov)
  • Therefore activities of the other kinases Erk, CK1 and GSK3β were tested after oloumucine treatment. (frontiersin.org)
  • Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. (nih.gov)
  • The molecule belongs to the cyclin-dependent kinase family. (wikipedia.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)
  • Receptor-interacting protein kinase 1 (RIPK1), a key molecule mediating necroptosis and regulated by transforming growth factor β-activated kinase 1 (TAK1), was reported to be associated with cognitive impairment in several neurodegenerative diseases. (imperial.ac.uk)
  • Mild stress-activated TP53 transcriptionally induced FBXO22, which in turn ubiquitinated KDM4B (lysine-specific demethylase 4B) complexed with MYC-NCOR1 suppressors for degradation, leading to transcriptional induction of TFEB. (elsevierpure.com)
  • Group 3 cyclins (G1, G2 and I) may play a role distinct from either cell cycle or transcriptional regulation. (bdbiosciences.com)
  • 2. E2F is released when RB is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex, 3. (ctsqena.com)
  • Surprisingly, purified and endogenous phosp27-CDK4-CycD1 complexes were insensitive to the CDK4-targeting drug palbociclib. (rcsb.org)
  • Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors. (rcsb.org)
  • 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)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • The Zhou laboratory is interested in understanding the epigenetic mechanisms that integrate environmental factors with the genetic code to govern brain development and function, elucidating the pathophysiology of specific neurodevelopmental disorders with known genetic causes such as Rett syndrome and CDKL5 deficiency, and illuminating the pathogenesis of selective neuropsychiatric disorders with complex genetic traits such as autism and major depression. (upenn.edu)
  • The expression of FTO, Proliferating cell nuclear antigen, Cyclin D1, B-cell lymphoma 2 (Bcl2) and BCL2 assaciated X was detected by Western blot and Real-time quantitative polymerase chain reaction, respectively. (bvsalud.org)
  • The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. (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)
  • Like many cyclins, the expression of cyclin C oscillates throughout the cell cycle, with a peak observed during G1 phase. (bdbiosciences.com)
  • West syndrome is an age-dependent expression of a damaged brain, and most patients with infantile spasms have some degree of developmental delay. (medscape.com)
  • Some investigations have reported that the active states of protein kinases structurally differ from each other in order to preserve the geometry of its machinery so that catalytic output works properly. (wikipedia.org)
  • One critical step involves recruitment of the pre-assembled U4/U6.U5 tri-snRNP to Complex A, which engages 5′ and 3′ splice sites, to form the pre-catalytic Complex B. Complex B then undergoes profound structural and conformational changes that lead to catalytic activation and conversion to Complex B act , which initiates catalysis and nucleates the formation of Complex C, which completes the splicing reaction [ 3 , 4 ]. (biomedcentral.com)
  • These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. (johnshopkins.edu)
  • They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
  • Protein kinases represent promising anticancer drug targets. (rcsb.org)
  • Of these, indirubin-3'-monoxime, SP 600125, KT 5823 and ML-9 were found to inhibit a number of protein kinases and conclusions drawn from their use in cell-based assays are likely to be erroneous. (nih.gov)
  • Cytochrome c leaks from the mitochondria activating apoptosis, 3. (ctsqena.com)
  • 3. B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma. (ctsqena.com)
  • Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. (hindawi.com)
  • Recent reports have indicated that terpinen-4-ol exerts its antitumor effects by triggering caspase-dependent apoptosis in human melanoma cells or by inducing necrotic cell death and cell-cycle arrest in mouse mesothelioma and melanoma cell lines without affecting normal cells [ 14 , 15 ]. (hindawi.com)
  • Our results indicated that terpinen-4-ol induced apoptosis through a mitochondria-mediated pathway in NSCLC cells and that the apoptosis elicited by terpinen-4-ol was p53 dependent. (hindawi.com)
  • Interestingly, PTHrP(12-48) treatment dose-dependently suppressed osteoclastogenesis, via the induction of apoptosis in both OCL precursors as well as in mature OCLs, as measured by the activation of cleaved caspase 3. (phoenixpeptide.com)
  • Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a time- and concentration-dependent manner. (mdpi.com)
  • 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)
  • 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)
  • The genetic underpinnings of neuropsychiatric disorders are highly complex, involving multifaceted interactions between risk genes and the environment. (upenn.edu)
  • We performed additional in silico analyses to identify more evidence for the associated variants and genes in relation to the plasma MPO-DNA complex levels. (frontiersin.org)
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • a metabolic energy sensor or cellular fuel gauge), tuberous sclerosis complex (TSC), and mammalian target of rapamycin (mTOR). (biomedcentral.com)
  • It is found as a subunit of protein complexes that are in involved in the enzymatic modification of histones including the Mi2 and Sin3 histone deacetylase complexes and the polycomb repressive complex 2. (lookformedical.com)
  • This triggered an increase in paracellular permeability via cellular redistribution of claudin 3 (CLDN3) from TJs into cell nuclei followed by disruption of epithelial integrity and formation of epithelial lesions. (springer.com)
  • Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation. (johnshopkins.edu)
  • Increased sub-G1 population and annexin-V binding, activation of caspases 9 and 3, cleavage of poly(ADPribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated involvement of the mitochondrial apoptotic pathway in terpinen-4-ol-treated A549 and CL1-0 cells. (hindawi.com)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • TGF-β1 binding to either subunit initiates their assembly into a heteromeric protein complex that consists of two type I and two type II subunits. (springer.com)
  • Therefore, binding with the activator is sufficient to activate the kinase. (wikipedia.org)
  • Mutations in either BUR1 cyclin-dependent kinase or the associated BUR2 cyclin resulted in short telomeres. (johnshopkins.edu)
  • Western blot analysis of extracts from Akt1 (lane 1), Akt2 (lane 2) and Akt3 (lane 3) knock-out mouse embryonic fibroblasts (MEFs) and matched wild-type MEFs (lane 4) using Akt1 (C73H10) Rabbit mAb (upper) and Akt2 Antibody #2962 (lower). (cellsignal.com)
  • Western blot analysis of cyclin C in NIH 3T3 mouse fibroblasts. (bdbiosciences.com)
  • The core spliceosome component PRPF8 is essential for spliceosome assembly through its participation in ribonucleoprotein (RNP) complexes for splice-site recognition, branch-point formation and catalysis. (biomedcentral.com)
  • The activation of the kinase function is then followed by a cascade of protein phosphorylations that promotes the transition through the cell-cycle checkpoint from the G 1 phase into the S phase ( 3 ). (iiarjournals.org)
  • We performed a genome-wide association study (GWAS) and exome-sequencing analysis to identify common and rare genetic variants associated with plasma myeloperoxidase (MPO)-DNA complex levels, a biomarker for NETs, in the population-based Rotterdam Study cohort. (frontiersin.org)
  • It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)
  • 4, Cell cycle regulators mediate progression through the cell cycle {e.g., cyctin and cyclin-dependent kinase). (ctsqena.com)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)
  • More recently, cyclins are being shown to have additional functions not restricted to cell cycle regulation. (bdbiosciences.com)
  • Cyclin I is an atypical cyclin because it is most abundant in postmitotic cells. (jci.org)
  • The A allele codes for a truncated variant, cyclin D1b, which may have higher transforming activity. (iiarjournals.org)
  • This truncated variant, cyclin D1b, does not have the part which is required for export from the nucleus into other cell localizations and therefore has higher transforming activity ( 8 ). (iiarjournals.org)
  • No. 558903) was titrated from 1:4000 to 1:12,000 (lanes 1 to 3) and identifies cyclin at ~ 36 kD. (bdbiosciences.com)
  • 17 Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands. (nih.gov)
  • During MD simulations, a trajectory, of conformations of a protein alone or in complex with other, molecular entities in a given biological environment is calculated, a bridge between theory and experiment. (cynioch.pl)