KinasesCDKsPhosphorylationProteinsCDK4Novel cyclin-dependIncluding D-type cyclinsMitoticKinase InhibitorCdc2MitosisInhibitionCdk1ProgressionComplexesActivity of this kinaseTransitionCKIsCdk2Transcriptional regulationReplicationDependentArrestApoptosisRibociclibPolymeraseAccumulationGeneFibroblastsEukaryotesActivationInhibitsTranscriptionEnzymesAmino acidsCdc28Targets
Kinases10
- Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (nature.com)
- 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)
- 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)
- 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)
- Cyclin-dependent kinases (CDKs), are members of the serine-threonine protein kinase family and are responsible for taking control of cell cycle regulation in eukaryotic cells. (spandidos-publications.com)
- Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)
- 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)
- Palbociclib and ribociclib are cyclin-dependent kinases (CDK) 4, 6 inhibitors indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. (medscape.com)
CDKs4
- 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)
- 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)
- CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
Phosphorylation11
- Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. (wikipedia.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)
- Phosphorylation of Clb5-specific targets during S phase was reduced by replacing Clb5 with Clb2 or by mutating the substrate RXL motif, confirming the importance of Clb5 specificity in vivo . (nature.com)
- Thus, Clb5 and Clb2 use distinct mechanisms to enhance the phosphorylation of S-phase and M-phase substrates. (nature.com)
- Activation of CDK4 requires binding of a D-type Cyclin and phosphorylation of Thr172 by the CAK kinase complex. (rndsystems.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. (proteopedia.org)
- 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)
- USP37 is activated by phosphorylation and thus triggers G1-S transition. (proteopedia.org)
- Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. (proteopedia.org)
Proteins5
- Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a), CDKN2A and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
- The Clb5-specific targets include several proteins (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events. (nature.com)
- 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)
- In the hippocampus, one of the first areas affected by the disease, both AD and MCI samples had robust staining for cyclin D1, DNA polymerase, and cyclin B1, proteins that are synthesized only during the G1, S and G2 phases of the cell cycle, respectively. (alzforum.org)
CDK411
- Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene. (wikipedia.org)
- CDK4 is a member of the cyclin-dependent kinase family. (wikipedia.org)
- Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
- Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
- Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
- It is regulated by Cyclin D. Ribociclib are US FDA approved CDK4 and CDK6 inhibitors for the treatment of estrogen receptor positive/ HER2 negative advanced breast cancer. (wikipedia.org)
- The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. (nih.gov)
- This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D1, Cdk4, INK4a and INK4b, pRb etc. (nih.gov)
- Cyclin-dependent Kinase 4 (CDK4) is a 303 amino acid (aa) member of the Ser/Thr kinase family with a predicted molecular weight of 33.7 kDa. (rndsystems.com)
- The CDK4/Cyclin D complex is also negatively regulated by p21/CIP1/CDKN1A and p27/Kip1. (rndsystems.com)
- Consistent with these results, PMFs and ATST combinations decreased expression levels of phospho Rb, cyclin D1, and CDK4. (umass.edu)
Novel cyclin-depend1
- 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)
Including D-type cyclins1
- The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)
Mitotic5
- It has been suggested that once cells pass Start, Cln proteolysis is triggered by the mitotic cyclins Clb1, 2, 3 and 4 (ref. 6). (uky.edu)
- Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)
- Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
- Mitotic cyclins stably associate with CDC2 and function as regulatory subunits. (caslab.com)
- Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
Kinase Inhibitor1
- Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. (koreamed.org)
Cdc24
- Stern, B. & Nurse, P. A quantitative model for the cdc2 control of S phase and mitosis in fission yeast. (nature.com)
- Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (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)
- CDC2 is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF) , which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. (caslab.com)
Mitosis2
- 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. (proteopedia.org)
- It is required in higher cells for entry into S-phase and mitosis. (caslab.com)
Inhibition6
- It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21 Cip/Waf and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. (nature.com)
- Anticancer effects of the HDAC inhibitor, 3β,6β‑dihydroxyurs‑12‑en‑27‑oic acid, in MCF‑7 breast cancer cells via the inhibition of Akt/mTOR pathways. (iasp-pain.org)
- 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)
- Escape from G1 arrest during acute MEK inhibition drives the acquisition of drug resistance. (babraham.ac.uk)
- This suggests that DNA replication following escape from G1 arrest in drug is more error prone and provides a potential explanation for the DNA damage observed under long-term RAF-MEK-ERK1/2 pathway inhibition. (babraham.ac.uk)
- The inhibition of cell proliferation was related to arrest of the cell cycle in the G0/G1 phase and increased apoptosis in response to PTGR1 knockdown as indicated by flow cytometry. (go.jp)
Cdk11
- Targets of the cyclin-dependent kinase Cdk1. (nature.com)
Progression4
- CLN transcription is modulated by physiological signals that regulate G1 progression, but it is unclear whether Cln protein stability is cell- cycle-regulated. (uky.edu)
- It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.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)
- Approval of palbociclib for initial endocrine-based therapy in postmenopausal women was based on the phase II trial (PALOMA-1) which measured median progression-free survival (PFS) duration. (medscape.com)
Complexes2
- A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
- p27 is a protein that binds to and prevents the activation of different G1 and S phase cyclin-CDK complexes. (lu.se)
Activity of this kinase1
- The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. (wikipedia.org)
Transition2
- It promotes the transition from G1 to S phase by phosphorylating and inactivating RB1. (rndsystems.com)
- Focusing on cyclin D1 as a major cell cycle regulator, we present evidence that a crucial cell cycle function of cyclin D1 is to prevent the transition into quiescence and identify a unique cyclin D1 protein kinetics that are indicative of very short G1 phases. (cam.ac.uk)
CKIs1
- 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)
Cdk24
- Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
- Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (proteopedia.org)
- Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
- We hypothesize that a dynamic equilibrium between the dominant buried state and an transiently open, kinase-accessible state is present in the p27-cyclin A-CDK2 complex, and aim to test this hypothesis through the use of unbiased molecular dynamics and metadynamics simulations. (lu.se)
Transcriptional regulation2
- Cln instability thus provides a means to couple Cln-Cdc28 activity to transcriptional regulation and protein synthetic rate in pre-Start G1 cells. (uky.edu)
- Group 3 cyclins (G1, G2 and I) may play a role distinct from either cell cycle or transcriptional regulation. (bdbiosciences.com)
Replication1
- Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
Dependent8
- Start is triggered by the cyclin- dependent kinase Cdc28 and three rate-limiting activators, the G1 cyclins Cln1, Cln2 and Cln3 (ref. 3). (uky.edu)
- Roscovitine is a cyclin-dependent kinase (cdk) inhibitor. (tocris.com)
- Schulman, B. A., Lindstrom, D. L. & Harlow, E. Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. (nature.com)
- Cell-cycle arrest was associated with the engagement of checkpoint kinase 2-cell division cycle 25C-cyclin-dependent kinase 1/cyclin B1 signaling. (bioone.org)
- Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. (koreamed.org)
- Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. (koreamed.org)
- ACT‑3 significantly reduced the expression levels of cyclin D1 and cyclin‑dependent kinase 4, and upregulated the expression levels of p21 and p53. (iasp-pain.org)
- Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. (bvsalud.org)
Arrest5
- Moreover, cell cycle arrest at G0/G1 phase was triggered by decreased LAPTM5 as well, which could lead to delayed BCa cell growth. (spandidos-publications.com)
- Taken together, our results suggested that decreased LAPTM5 inhibited proliferation and viability, as well as induced G0/G1 cell cycle arrest possibly via deactivation of ERK1/2 and p38 in BCa cells. (spandidos-publications.com)
- Flow cytometry analysis showed that both NBT/ATST and TAN/ATST combinations caused significant cell cycle arrest at G0/G1 phase in MDAMB231 cells (ER+). (umass.edu)
- To test the hypothesis that escape from G1 arrest in drug promotes amplification, we exploited the combination of palbociclib and selumetinib. (babraham.ac.uk)
- Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
Apoptosis2
- JAM3 knockdown additionally inhibited trophoblast proliferation and increased the number of trophoblasts in the sub-G1 and G2/M phases, indicating cell-cycle disturbance and apoptosis. (bioone.org)
- A significant increase in the G1 phase cell population was observed in MCF‑7 cells and ACT‑3 induced apoptosis by reducing the ratio of B‑cell lymphoma‑2 (Bcl‑2)/Bcl‑2‑associated X (Bax) and releasing cleaved caspase 9. (iasp-pain.org)
Ribociclib1
- Approval of ribociclib was based on interim analysis results from the pivotal phase 3 MONALEESA-2 trial in postmenopausal women who received no prior systemic therapy for their advanced breast cancer. (medscape.com)
Polymerase1
- Though they caution that the precise anatomical location of the samples varied from case to case, which could introduce some margin of error, the number of DNA polymerase- and cyclin D1-positive neurons were identical in both MCI and AD tissues, at five percent. (alzforum.org)
Accumulation1
- Cyclin accumulation in G1 is driven in part by the cell-cycle-regulated transcription of CLN1 and CLN2, which peaks at Start. (uky.edu)
Gene3
- The molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). (medscape.com)
- 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)
Fibroblasts1
- Western blot analysis of cyclin C in NIH 3T3 mouse fibroblasts. (bdbiosciences.com)
Eukaryotes1
- In most eukaryotes, commitment to cell division occurs in late G1 phase at an event called Start in the yeast Saccharomyces cerevisiae, and called the restriction point in mammalian cells. (uky.edu)
Activation1
- ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
Inhibits1
- Inhibits M phase promoting factor (MPF) kinase activity. (enzolifesciences.com)
Transcription1
- It acts as a transcription repressor of E2F target genes, whose activity is required for progress from the G1 to the S phase of the cell cycle. (nih.gov)
Enzymes1
- 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)
Amino acids1
- 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)
Cdc281
Targets1
- p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. (kegg.jp)