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)
The protein encoded by this gene is a member of the Ser/Thr protein kinase family. (wikipedia.org)
It is a catalytic subunit of the protein kinase complex that is important for cell cycleG1 phase progression. (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)
Overexpression of the RNA-binding protein HuR (ELAVL1) occurs during colon tumorigenesis and is abnormally present within the cytoplasm, where it post-transcriptionally regulates genes through its interaction with 3'UTR AU-rich elements (AREs). (oncotarget.com)
Orthologous to human CDK2AP1 (cyclin dependent kinase 2 associated protein 1). (nih.gov)
UBF may activate rDNA transcription by recruiting Pol I towards the rDNA promoter stabilizing binding of SL1 and contending with nonspecific DNA binding protein such as for example histone H1 (21). (cancerrealitycheck.com)
p18INK4C Protein is suitable for use in Western Blot and Kinase Assay. (rockland.com)
Apigenin reduced CCAAT/enhancer binding protein (C/EBP) α and peroxisome proliferator-activated receptor γ levels. (kist.re.kr)
In addition, apigenin inhibited the DNA-binding activity of C/EBPβ in differentiating 3T3-L1 cells by down-regulating the 35 kDa isoform of C/EBPβ (liver-enriched activating protein) and up-regulating the expression of two different sets of C/EBP inhibitors: C/EBP homologous protein and the phospho-liver-enriched inhibitory protein isoform of C/EBPβ. (kist.re.kr)
The researchers sought to develop a drug that inhibits a protein called cyclin-dependent kinase 2 (CDK2), which belongs to the cyclin-dependent kinase protein family. (technologynetworks.com)
Western blotting was performed to detect the protein levels of cyclin‑dependent kinase inhibitor P21 (P21), B‑cell lymphoma‑2 (Bcl‑2), matrix metalloproteinase 9 (MMP9) and E26 oncogene homolog 1 (ETS1). (spandidos-publications.com)
p27 is a protein that binds to and prevents the activation of different G1. (lu.se)
Homo sapiens CGG triplet repeat binding protein 1 (CGGBP1), transcript variant 1, mRNA. (dbcls.jp)
Protein phosphatase 2A (PP2A) also binds separase but the physiological role of this interaction remains enigmatic. (uni-bayreuth.de)
The p16(INK4A) protein attaches (binds) to two other proteins called CDK4 and CDK6. (medlineplus.gov)
BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. (lu.se)
Inhibitors9
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)
Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (prospecbio.com)
2018) Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors. (guidetopharmacology.org)
2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. (guidetopharmacology.org)
Although options for the treatment of ER-positive metastatic breast cancer have evolved considerably, perhaps the most striking development in recent years has been the advent of potent tyrosine kinase inhibitors that selectively bind to cyclin-dependent kinases 4 and 6 (CDK4/6) and block the cell-cycle transition from the G1 phase to the S phase. (nejm.org)
Although ESR1 mutations confer estrogen independence (and therefore potential resistance to aromatase inhibitors), tumors with ESR1 mutations are still ER-dependent and could be inhibited by drugs that target the ER directly, such as fulvestrant. (nejm.org)
Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
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)
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)
UBF1 is normally turned on during G1 development by phosphorylation of serine 484 by cdk 4/cyclin D1 (42) and serine 388 by cdk2/cyclin E and A (41) leading to complete activation of rRNA transcription. (cancerrealitycheck.com)
Georg and colleagues identified a previously unknown site in CDK2 and a dye molecule that binds to it. (technologynetworks.com)
They selected one molecule for further optimization: EF-4-177, which bound to CDK2 more strongly than the dye. (technologynetworks.com)
Activation of the CDK2-cyclin E complex results in hyperphosphorylation of Rb and fully releases E2F. (shu.edu)
Phosphorylation7
This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (wikipedia.org)
Activation of CDK4 requires binding of a D-type Cyclin and phosphorylation of Thr172 by the CAK kinase complex. (rndsystems.com)
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)
During early G1 phase, mitogenic signals trigger activation of the CDK4/6-cyclin D complex, which partially deactivates Rb by phosphorylation. (shu.edu)
The p16 family (p15, p16, p18 and p19) binds to and inhibits the activities of CDK4 and CDK6. (prospecbio.com)
The 113insArg mutant p16(INK4a) was unable to bind cdk4 and cdk6 in an in vitro binding assay. (lu.se)
Early G1 phase1
6) Upon destruction of this last cyclin B1 in early G1 phase, separase is released from the late Cdk1-cyclin B1-separase complex and triggers centriole disengagement, thereby licensing later centrosome duplication. (uni-bayreuth.de)
Proteins6
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)
Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. (hindawi.com)
SL1 a proteins Sotrastaurin (AEB071) complex filled with the TATA-binding proteins (TBP) and three Pol I-specific TBP-associated elements (TAFs) (9) confers promoter specificity. (cancerrealitycheck.com)
The participation of most three proteins have already been described as getting in charge of cell routine through alteration of or connections with key mobile regulator proteins such as for example p53 p21 cyclins aswell as transcription elements proto-oncogenes and development elements/ cytokines (20). (cancerrealitycheck.com)
NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. (oncotarget.com)
CDKN2A1
0001). Families with breast cancer also had a propensity for multiple melanomas in females, suggesting that a sex-dependent factor may modify the phenotypic expression of CDKN2A alterations. (lu.se)
Palbociclib1
Ibrance (palbociclib) is an inhibitor of cyclin-dependent kinase (CDK) 4 and 6. (shu.edu)
Mutation1
Dr. Gray has also developed structure-based, generalized approaches for designing drugs to overcome one of the most common mechanisms of resistance observed against most kinase inhibitor drugs, mutation of the so-called 'gatekeeper' residue, which has been observed in resistance to drugs targeting BCR-ABL, c-KIT and PDGFR. (stanford.edu)
Gene1
4. Both copies of Rb gene must be knocked out for tumor formation (Knudson twohit hypothesis). (ctsqena.com)
Inhibit3
The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (prospecbio.com)
Plumbagin, for example, was shown to inhibit the DNA-binding activity of NF-B and induce apoptosis in triple-negative MDA-MB-231 breast tumor cells (20). (unambitiousus.com)
It is enabled by SAC-activated Mad2 to bind and inhibit separase and can functionally replace securin. (uni-bayreuth.de)
Cdk14
Targets of the cyclin-dependent kinase Cdk1. (nature.com)
Separase can alternatively be inhibited by association with Cdk1-cyclin B1 but the corresponding complex is scarce in early mitosis and cannot explain why vertebrate securin is dispensable. (uni-bayreuth.de)
4) Pin1 catalyzed trans-to-cis isomerization of separase is essential for Cdk1-cyclin B1-dependent inhibition and explains why the kinase and securin bind separase in a mutually exclusive manner. (uni-bayreuth.de)
Dephosphorylation results in a second peak of Cdk1-cyclin B1-separase complex formation in late mitosis when most cyclin B1 has already been degraded. (uni-bayreuth.de)
Receptor1
Receptor binding causes GDP to be replaced with GTP, activating ras. (ctsqena.com)
Mitosis2
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)
While free securin is phosphorylated in mitosis, separase-bound securin is kept in an unphosphorylated state by associated PP2A. (uni-bayreuth.de)
Complexes2
Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
CDK4 may be useful as a prognostic marker for hepatocellular carcinoma and its kinase activity has been reported to promote the progression of T cell acute lymphoblastic leukemia. (rndsystems.com)
The expression of further E2F target genes, as cyclin A, facilitates progression through S phase. (shu.edu)
4, Cell cycle regulators mediate progression through the cell cycle {e.g., cyctin and cyclin-dependent kinase). (ctsqena.com)
Aberrant changes in epigenetic mechanisms regulating DNA methylation, histone methylation and acetylation, expression of noncoding RNAs, and mRNA methylation are associated with the initiation, growth, and progression of digestive system tumors [ 2 , 4 ]. (ijbs.com)
However, binding of p16(INK4A) blocks CDK4's or CDK6's ability to stimulate cell cycle progression. (medlineplus.gov)
Selectively1
Using the dye, they screened several thousand compounds to identify any that selectively target the binding site. (technologynetworks.com)
P16INK4a1
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)
Assay1
Our results indicated that terpinen-4-ol elicited a dose-dependent cytotoxic effect, as determined by MTT assay. (hindawi.com)
Apoptosis5
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)
Collectively, these data provide insight into the molecular mechanisms underlying terpinen-4-ol-induced apoptosis in NSCLC cells, rendering this compound a potential anticancer drug for NSCLC. (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)
It was identified that propofol inhibited the viability and invasion, but promoted apoptosis of HGC‑27 and AGS cells in a dose‑dependent manner. (spandidos-publications.com)
Activation3
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)
Activation of the VEGFA/VEGFR2 signaling and expression of blood vascular endothelial cell (BEC) markers, such as NRP1 and EphrinB2, further differentiate these precursor cells into BECs, which then form the hierarchical network of blood vessels 4 . (nature.com)
The NS5A-dependent IL25 antibody activation of rRNA transcription is apparently because of hyperphosphorylation and consequent activation of upstream binding aspect (UBF) a Pol I DNA binding transcription aspect. (cancerrealitycheck.com)
Complex4
Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
The CDK4/Cyclin D complex is also negatively regulated by p21/CIP1/CDKN1A and p27/Kip1. (rndsystems.com)
These kinases are expressed throughout the cell cycle, but are only activated upon complex formation with their corresponding cyclins. (shu.edu)
2. E2F is released when RB is phosphorylated by the cyclinD/cyclin-dependent kinase 4 (CDK4) complex, 3. (ctsqena.com)
Substrate2
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)
Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
Although these findings demonstrate the anticancer activity of terpinen-4-ol, the underlying molecular mechanisms of the antitumor activity of terpinen-4-ol remain unclear. (hindawi.com)
Predicted to enable DNA polymerase binding activity. (nih.gov)
Mitotic1
Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phasecyclins in replication origin firing. (nature.com)
Transcription initiation by individual RNA Pol I needs at least two elements furthermore to Pol I: the upstream binding aspect 1 (UBF1) and a species-specific aspect SL1. (cancerrealitycheck.com)
Mutations1
ESR1 mutations in the ligand-binding domain of the ER result in constitutively active ER conformation and confer estrogen-independent but ER-dependent signaling. (nejm.org)
Human5
In this study, the antitumor effects of terpinen-4-ol and the cellular and molecular mechanisms responsible for it were evaluated and studied, respectively on human nonsmall cell lung cancer (NSCLC) cells. (hindawi.com)
In addition, there is no report on the antitumor effects of terpinen-4-ol against human nonsmall cell lung cancer cells. (hindawi.com)
Therefore, in this study, the anticancer effects of terpinen-4-ol were evaluated on two NSCLC cell lines, namely, A549 and CL1-0 human lung adenocarcinoma cells. (hindawi.com)
ABCB5 is a poorly characterised member of the B-subfamily of human ATP Binding Cassette transporters. (qmul.ac.uk)
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human Cdkn3 - N-terminal region. (bioworldantibodies.com)
Mediate2
Subsequently released E2F factors mediate expression of pro-proliferative genes including cyclin E and Cdc25A. (shu.edu)
Silencing of the spindle assembly checkpoint (SAC) in metaphase enables the ubiquitin ligase APC/C to mediate the proteasomal destruction of securin (and cyclin B1), thereby activating separase. (uni-bayreuth.de)