The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. (proteopedia.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)
Cell cycle regulation is largely based on protein phospho-dephosphorylation events, catalyzed by cyclin dependent kinases (Cdks) and phosphatases (PPases), respectively. (encyclopedia.pub)
Most kinase inhibitors work on tyrosine kinases . (callaix.com)
Tyrosine kinase inhibitors (TKIs) are a class of chemotherapy medications that inhibit, or block, one or more of the enzyme tyrosine kinases. (callaix.com)
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
CDKs are cyclin-dependent serine-/threonine-specific proteins kinases, the experience of which depends upon cyclin binding. (niepokorny.org)
The CDK1 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)
Phosphorylation9
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)
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)
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)
Cdc55 counteracts the Cdk1 phosphorylation of the APC/C subunit Cdc16 [ 11 ] [ 10 ] , keeping the spindle checkpoint assembly (SAC) active until the cell is prepared for anaphase. (encyclopedia.pub)
Studies with Mcl-1 phosphorylation mutants show that cyclin E/Cdk2-dependent phosphorylation of Mcl-1 residues on its PEST domain resulted in increased Mcl-1 stability (Thr92, and Thr163) and Bim binding (Ser64). (oncotarget.com)
Substrates3
Figure 1: Identification of Clb5-specific Cdk1 substrates in budding yeast. (nature.com)
Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
Furthermore to people indirect results on cell routine legislation, the viral proteins kinase pUL97 straight cross-talks with CDKs since it mimics CDKs in phosphorylating partly-identical substrates and evidently possesses commonalities in protein framework and functionality. (niepokorny.org)
Progression2
In addition with their main function in the legislation of cell routine progression, particular types of CDKs and cyclins get excited about transcription also, splicing, epigenetic legislation, neuronal features, stem cell regeneration, spermatogenesis, and differentiation [10]. (niepokorny.org)
CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. (umbc.edu)
Serine1
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes-like. (umbc.edu)
CDK28
The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. (cancerindex.org)
We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. (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)
In HCMV-infected cells, particular subsets of CDK-cyclin complexes are downregulated/suppressed (CDK4-cyclin D, CDK6-cyclin D, CDK2-cyclin A) or upregulated/turned on (CDK1-cyclin B, CDK2-cyclin E), leading to an early on S stage arrest termed pseudomitosis [11] eventually. (niepokorny.org)
Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (oncotarget.com)
Here, we show that cyclin E/Cdk2 phosphorylates and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). (oncotarget.com)
Cyclin E levels were elevated and there was increased association of cyclin E/Cdk2 with Mcl-1 in ABT-737-resistant compared to parental cells. (oncotarget.com)
Mitotic3
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 phasecyclins in replication origin firing. (nature.com)
Stern, B. & Nurse, P. A quantitative model for the cdc2 control of S phase and mitosis in fission yeast. (nature.com)
CDK91
Furthermore, we previously confirmed the fact that selective CDK9 and CDK7 inhibitors R22 and LDC4297 exert solid anticytomegaloviral activity in cell lifestyle versions [9]. (niepokorny.org)
Interacts2
Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. (cancerindex.org)
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)
Here we present an overview of the protein phosphatase 2A family's roles during mitosis. (encyclopedia.pub)
An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
Current scientific trials are looking into cyclin-dependent kinase (CDK) inhibitors, such as for example roscovitine, an inhibitor of CDK1, -2, -5, -7, and -9, that lowers viral DNA synthesis, creation of late protein and infectious pathogen particles [4]. (niepokorny.org)
Cyclin E depletion in various human tumor cell-lines and cyclin E -/- mouse embryo fibroblasts showed decreased levels of Mcl-1 protein, with no change in Mcl-1 mRNA levels. (oncotarget.com)
In the absence of cyclin E, Mcl-1 ubiquitination was enhanced, leading to decreased protein stability. (oncotarget.com)
CDK71
Along with CDK1 and -2, CDK7 and -9 are necessary for effective HCMV replication and had been discovered upregulated in HCMV-infected cells [3,12,13,14,15]. (niepokorny.org)
Proteins3
About 24% of these proteins were phosphorylated more efficiently by Clb5-Cdk1 than Clb2-Cdk1. (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)
Replication1
The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
Degradation1
It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. (umbc.edu)
CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. (umbc.edu)
20012
The first kinase inhibitor introduced for cancer was imatinib, which the FDA approved in 2001. (callaix.com)
An article published in the journal Molecular Cancer in 2018 claimed that over 10,000 patents had been filed in the US for kinase inhibitors since 2001. (callaix.com)
Targets2
Targets of the cyclin-dependent kinase Cdk1. (nature.com)
Extremely, CDKs and pUL97 phosphorylate Rb at similar residues [17,26]. (niepokorny.org)
Apoptosis2
In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. (umbc.edu)
Activation of CDK1 may contribute to HIV-1 induced apoptosis and neuronal apoptosis in neurodegenerative diseases. (umbc.edu)
Tumor1
Cyclin E knock-down restored ABT-737 sensitivity to acquired and inherently resistant Mcl-1-dependent tumor cells. (oncotarget.com)
Regulation1
Collectively, our findings identify a novel mechanism of cyclin E-mediated Mcl-1 regulation that provides a rationale for clinical use of Bcl-2 family and Cdk inhibitors for Mcl-1-dependent tumors. (oncotarget.com)
Genes1
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)
Increases1
Moreover, the identification of fork protection as a key mechanism of resistance to chemo- and poly (ADP-ribose) polymerase inhibitor therapy in ovarian cancer further increases the priority that should be accorded to the development of strategies targeting replicative stress. (bmj.com)
Activity2
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)
Furthermore, partially overlapping features between CDKs and pUL97 had been also postulated in light from the discovering that ADOS the HCMV-inhibitory aftereffect of the pUL97 inhibitor maribavir (MBV) was elevated when CDK activity was concurrently suppressed [11]. (niepokorny.org)
Phase3
CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. (umbc.edu)
The CDK1/cyclin B complex is critical for G2 to M phase transition. (umbc.edu)
M any kinase inhibitor compounds have been found. (callaix.com)
Higher1
This subfamily is composed of CDK1 from higher eukaryotes. (umbc.edu)
Main1
During many years the Cdks were considered the main component of the cell cycle control system. (encyclopedia.pub)
Potential1
Combined, the results demonstrate the potential of this new inhibitors series for further development into CDK-specific chemical probes or therapeutics. (proteopedia.org)
Major1
Kinase inhibitors are now one of the major categories of chemotherapy medicine. (callaix.com)
Development1
Over 50 kinase inhibitors are approved in the US for cancer treatment with more under development. (callaix.com)