Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. (rcsb.org)
OBJECTIVE: To review preclinical and clinical information on flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs), tested as an antitumor agent. (usuhs.edu)
Cyclin dependent kinases (CDKs) phosphorylate several substrates such as transcription factors and cytoskeletal proteins, which leads to the transition of the cell into the next cell cycle phase. (onkoview.com)
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)
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)
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)
P27KIP11
Cyclin-dependent kinase inhibitor p27Kip1 expression and interaction with other cell cycle-associated proteins in mammary carcinoma. (ox.ac.uk)
CDKs10
DATA SYNTHESIS: Flavopiridol is an inhibitor of several CDKs and displays unique anticancer properties. (usuhs.edu)
CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs). (biomedcentral.com)
Cyclins function as the positive regulators of CDKs. (biomedcentral.com)
D-type and E-type cyclins assemble with CDKs during the G1 phase and these holoenzymes act as rate-limiting controllers to regulate passage through the restriction point and the subsequent onset of DNA replication [ 2 , 3 ]. (biomedcentral.com)
Cyclins and CDKs assemble into complexes with one another as cells progress through G1 phase, cyclins being required to activate the serine-threonine kinase activity of their catalytic partners. (biomedcentral.com)
Furthermore, CDK-activating kinase (CAK) phosphorylates cyclin-bound CDKs on a single threonine residue, a modification that is essential for their activity [ 6 - 9 ]. (biomedcentral.com)
Cyclin-dependent kinase inhibitors (CDKIs) are proteins that bind to and inhibit the activity of CDKs. (biomedcentral.com)
Importantly, CDKs are inhibited by specific cyclin dependent kinase inhibitors. (onkoview.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)
CDK29
The new inhibitor is 1,000-fold more potent than the parent compound (K(i) values for CDK1 = 9 nM and CDK2 = 6 nM versus 5,000 nM and 12,000 nM, respectively, for O(6)-cyclohexylmethylguanine). (rcsb.org)
The increased potency arises primarily from the formation of two additional hydrogen bonds between the inhibitor and Asp 86 of CDK2, which facilitate optimum hydrophobic packing of the anilino group with the specificity surface of CDK2. (rcsb.org)
The work represents the first successful iterative synthesis of a potent CDK inhibitor based on the structure of fully activated CDK2-cyclin A. Furthermore, the potency of O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine was both predicted and fully rationalized on the basis of protein-ligand interactions. (rcsb.org)
Cdk2 promotes DNA replication and is a promising cancer therapeutic target, but its functions appear redundant with Cdk1, an essential Cdk affected by most Cdk2 inhibitors. (rcsb.org)
To confirm this we designed inhibitor-resistant (ir)-Cdk2 mutants using a novel bioinformatics approach. (rcsb.org)
Additionally, crystal structures and kinetics reveal alternative binding modes of Cdk1-selective and Cdk2-selective inhibitors and mechanisms of Cdk2 inhibitor resistance. (rcsb.org)
Cyclin E forms complexes during this interval with CDK2. (biomedcentral.com)
Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. (mdpi.com)
Recently, the first crystal structure of CDK2 with allosteric inhibitor has been reported, which provides new opportunities to design pure allosteric inhibitors of CDK2. (mdpi.com)
Cdkn2a2
We studied the roles of cyclin-dependent kinase inhibitors Cdkn2a and Cdkn2b, known as cellular stress-related senescence markers, in N-methyl-d-aspartate (NMDA)-induced RGC death. (elsevierpure.com)
also known as CDK4I, Cyclin-dependent kinase 4 inhibitor A, Multiple tumor suppressor 1, MTS-1, p16-INK4, p16-INK4a, p16INK4A) is encoded by the CDKN2A (also known as CDKN2, MTS1) gene (Gene ID 1029) in human. (sigmaaldrich.com)
Complexes5
Cyclin-dependent kinase inhibitor 1C is a tight-binding inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. (wikipedia.org)
The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.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)
CDK42
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)
Selective2
Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. (rcsb.org)
Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. (rcsb.org)
CDKIs2
The INK and CIP/KIP families of cyclin dependent kinase inhibitors (CDKis) protect cells from oncogenic signals-initiated cellular transformation. (sigmaaldrich.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)
Gene9
Cyclin-dependent kinase inhibitor 1C (p57, Kip2), also known as CDKN1C, is a protein which in humans is encoded by the CDKN1C imprinted gene. (wikipedia.org)
There was a statistically significant association between the expression of p27 and both cyclin D1 and the retinoblastoma gene product (pRb), corresponding to their close interactions in regulating the G1/S transition in the cell cycle. (ox.ac.uk)
Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. (biomedcentral.com)
A to MC-Val-Cit-PAB-carfilzomib fragment of pL3700.stop [22] was inserted into the corresponding region in the v-cyclin gene of pGS-3700.cycFdR, to create pGS-3700.cycFdR.stop, containing a translational stop linker, and referred to throughout text as gHV-cycKO. (galeriaespacio48.com)
Pre-exposure of cells to proteasome inhibitors blocked the Cd-induced inhibition of eIF4E gene expression as well as the resulting cytotoxicity and cell death. (cdc.gov)
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 D1gene 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)
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)
Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity. (cdc.gov)
Tumor1
Comparison of pre- and post-treatment paired tumor biopsies from patients treated with fulvestrant revealed an upregulation of cyclin E2 upon development of resistance. (lu.se)
Adjuvant2
This is going to give you a question to ponder in your high-risk, ER-positive patients who are appropriate to consider for adjuvant cyclin-dependent kinase inhibitors. (medscape.com)
5. Adjuvant treatment with CDK 4/6-inhibitors is allowed provided a disease-free interval from treatment end >12 months. (who.int)
INK41
An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. (childrensmercy.org)
CDKI1
PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). (biomedcentral.com)
Endogenous2
Inhibitor-1, the first identified endogenous inhibitor of protein phosphatase 1 (PP-1), was previously reported to be a substrate for cyclin-dependent kinase 5 (Cdk5) at Ser 67 . (elsevierpure.com)
Whereas only the viral cyclins can perform all v-cyclin dependent parameters of infection, our data also suggest that expression of endogenous host cyclins could complement v-cyclin-dependent functions in vivo. (galeriaespacio48.com)
Substrate Specificity1
These studies reveal that the unusual biochemical features of viral cyclins, such as broad substrate specificity and increased kinase activity, are not absolutely required to mediate specific processes within viral infection. (galeriaespacio48.com)
Kinase activity1
These data also indicate that v-cyclin features, such as resistance to cell cycle inhibitors or enhanced kinase activity, are necessary for optimal gammaherpesvirus pathogenesis. (galeriaespacio48.com)
Aromatase2
Premenopausal women and men also had an LHRH agonist in addition to an aromatase inhibitor - that could have been either letrozole or anastrozole - then randomized to ribociclib or placebo. (medscape.com)
A prior period of treatment with aromatase inhibitors or fulvestrant for up to 28 days from the CDK 4/6-inhibitor initiation is allowed. (who.int)
Inhibition1
In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. (usuhs.edu)
This led to an intensive development of small-molecule CDK9 inhibitors or new emerging strategies, such as proteolysis targeting chimeras (PROTACs). (rsc.org)
Fulvestrant2
Cyclin E2 overexpression was identified as a biomarker of a persistent fulvestrant-resistant phenotype. (lu.se)
Moreover, overexpression of this cyclin was found to be a prognostic factor determining resistance to fulvestrant and shorter progression-free survival. (lu.se)
In animals, CDK inhibitors are tightly regulated, especially by posttranslational mechanisms of which control of nuclear access and regulation of protein turnover are particularly important. (uni-bielefeld.de)
Here we address the posttranslational regulation of INHIBITOR/INTERACTOR OF CDK 1 (ICK1)/KIP RELATED PROTEIN 1 ( KRP1), an Arabidopsis ( Arabidopsis thaliana) CDK inhibitor. (uni-bielefeld.de)
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)
Cell5
Description: A sandwich ELISA for quantitative measurement of Human Cyclin dependent kinase inhibitor 3(CDKN3) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. (hudsen.org)
Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)
Notably, the studied models presented adaptation at different cell cycle nodes to facilitate progression through the cell cycle and responded differently to CDK inhibitors. (lu.se)
Resistance1
CONCLUSIONS: These data highlight the complexity of estrogen receptor positive breast cancer and suggest that the development of diverse resistance mechanisms dictate levels of ER independence and potentially cross-resistance to CDK inhibitors. (lu.se)
Phase1
D-type cyclins are usually synthesized by mid-G1 phase and accumulate to a maximum as cells advance through the G1/S boundary. (biomedcentral.com)
MeSH1
Cyclin-Dependent Kinase Inhibitor p18" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (childrensmercy.org)
Biochemical3
E) Purified genomic viral DNA was digested with biochemical studies corresponds to genetically distinct and required functions during virus infection, and that both the gHV68 and KSHV viral cyclins share this multifunctional capacity in infection. (galeriaespacio48.com)
Additionally, this study revealed distinct genetic complementation groups of the mammalian cyclins, demonstrating that mammalian cyclins can fulfill the biochemical features of the v-cyclin in infection. (galeriaespacio48.com)
And yet, cyclin D3 restored v-cyclin dependent reactivation less effectively than did the viral cyclins, suggesting that unique biochemical feature(s) of viral cyclins may be required to facilitate robust activity in reactivation. (galeriaespacio48.com)
Cancer1
Evidence Central , evidence.unboundmedicine.com/evidence/view/EBMG/1305408/all/Cyclin_dependent_kinase_inhibitor_for_advanced_breast_cancer. (unboundmedicine.com)
Expression2
DHA-enriched fish oil upregulates cyclin-dependent kinase inhibitor 2A (P16 INK ) expression and downregulates telomerase activity without modulating effects of PPARγ Pro12Ala polymorphism in type 2 diabetic patients: A randomized, double-blind, placebo-controlled clinical trial. (bvsalud.org)
When the combined expression of p27 and cyclin D1 was related to survival, patients with high levels of p27, regardless of their cyclin D1 status, did well, whilst those with low p27 had a poor outcome. (ox.ac.uk)
Absence1
This idea is consistent with our observations that neither persistent infection nor reactivation from latency is completely abrogated in absence of the v-cyclin. (galeriaespacio48.com)