Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
The sum of the weight of all the atoms in a molecule.
A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.
A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.
Cyclin-dependent kinase 6 associates with CYCLIN D and phosphorylates RETINOBLASTOMA PROTEIN during G1 PHASE of the CELL CYCLE. It helps regulate the transition to S PHASE and its kinase activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P18.
A potent inhibitor of CYCLIN-DEPENDENT KINASES in G1 PHASE and S PHASE. In humans, aberrant expression of p57 is associated with various NEOPLASMS as well as with BECKWITH-WIEDEMANN SYNDROME.
Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
Tumors or cancer of the human BREAST.
The profession of writing. Also the identity of the writer as the creator of a literary production.
Collections of facts, assumptions, beliefs, and heuristics that are used in combination with databases to achieve desired results, such as a diagnosis, an interpretation, or a solution to a problem (From McGraw Hill Dictionary of Scientific and Technical Terms, 6th ed).
An aberration in which a chromosomal segment is deleted and reinserted in the same place but turned 180 degrees from its original orientation, so that the gene sequence for the segment is reversed with respect to that of the rest of the chromosome.
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Mice which carry mutant genes for neurologic defects or abnormalities.
Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.
A cyclin subtype that is found associated with CYCLIN-DEPENDENT KINASE 9. Unlike traditional cyclins, which regulate the CELL CYCLE, type T cyclins appear to regulate transcription and are components of positive transcriptional elongation factor B.
A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.
Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults.

Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. (1/4016)

Telomerase is a ribonucleoprotein enzyme that adds hexanucleotide repeats TTAGGG to the ends of chromosomes. Telomerase activation is known to play a crucial role in cell-immortalization and carcinogenesis. Telomerase is shown to have a correlation with cell cycle progression, which is controlled by the regulation of cyclins, cyclin dependent kinases (cdks) and cyclin dependent kinase inhibitors (cdkis). Abnormal expression of these regulatory molecules may cause alterations in cell cycle with uncontrolled cell growth, a universal feature of neoplasia. Skin cancer is the most prevalent form of cancer in humans and the solar UV radiation is its major cause. Here, we investigated modulation in telomerase activity and protein expression of cell cycle regulatory molecules during the development of UVB-induced tumors in SKH-1 hairless mice. The mice were exposed to 180 mjoules/cm2 UVB radiation, thrice weekly for 24 weeks. The animals were sacrificed at 4 week intervals and the studies were performed in epidermis. Telomerase activity was barely detectable in the epidermis of non-irradiated mouse. UVB exposure resulted in a progressive increase in telomerase activity starting from the 4th week of exposure. The increased telomerase activity either persisted or further increased with the increased exposure. In papillomas and carcinomas the enzyme activity was comparable and was 45-fold higher than in the epidermis of control mice. Western blot analysis showed an upregulation in the protein expression of cyclin D1 and cyclin E and their regulatory subunits cdk4 and cdk2 during the course of UVB exposure and in papillomas and carcinomas. The protein expression of cdk6 and ckis viz. p16/Ink4A, p21/Waf1 and p27/Kip1 did not show any significant change in UVB exposed skin, but significant upregulation was observed both in papillomas and carcinomas. The results suggest that telomerase activation may be involved in UVB-induced tumorigenesis in mouse skin and that increased telomerase activity may be associated with G1 phase of the cell cycle.  (+info)

Comparative molecular genetic profiles of anaplastic astrocytomas/glioblastomas multiforme and their subsequent recurrences. (2/4016)

Malignant glial tumors (anaplastic astrocytomas and glioblastomas multiforme) arise mostly either from the progression of low grade precursor lesions or rapidly in a de novo fashion and contain distinct genetic alterations. There is, however, a third subset of malignant gliomas in which genetic lesions remain to be identified. Following surgical resection, all gliomas appear to have an inherent tendency to recur. Comparative molecular analysis of ten primary malignant gliomas (three anaplastic astrocytomas and seven glioblastomas multiforme) with their recurrences identified two distinct subgroups of recurrent tumors. In one group, primary tumors harbored genetic aberrations frequently associated with linear progression or de novo formation pathways of glial tumorigenesis and maintained their genetic profiles upon recurrence. In the other subset with no detectable known genetic mutations at first presentation, the recurrent tumors sustained specific abnormalities associated with pathways of linear progression or de novo formation. These included loss of genes on chromosomes 17 and 10, mutations in the p53 gene, homozygous deletion of the DMBTA1 and p16 and/ or p15 genes and amplification and/or overexpression of CDK4 and alpha form of the PDGF receptor. Recurrent tumors from both groups also displayed an abnormal expression profile of the metalloproteinase, gel A, and its inhibitor, TIMP-2, consistent with their highly invasive behavior. Delineation of the molecular differences between malignant glioblastomas and their subsequent recurrences may have important implications for the development of rational clinical approaches for this neoplasm that remains refractory to existing therapeutic modalities.  (+info)

The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis. (3/4016)

The first appearance of G1 during Drosophila embryogenesis, at cell cycle 17, is accompanied by the down-regulation of E2F-dependent transcription. Mutant alleles of rbf were generated and analyzed to determine the role of RBF in this process. Embryos lacking both maternal and zygotic RBF products show constitutive expression of PCNA and RNR2, two E2F-regulated genes, indicating that RBF is required for their transcriptional repression. Despite the ubiquitous expression of E2F target genes, most epidermal cells enter G1 normally. Rather than pausing in G1 until the appropriate time for cell cycle progression, many of these cells enter an ectopic S-phase. These results indicate that the repression of E2F target genes by RBF is necessary for the maintenance but not the initiation of a G1 phase. The phenotype of RBF-deficient embryos suggests that rbf has a function that is complementary to the roles of dacapo and fizzy-related in the introduction of G1 during Drosophila embryogenesis.  (+info)

Coupling of the cell cycle and myogenesis through the cyclin D1-dependent interaction of MyoD with cdk4. (4/4016)

Proliferating myoblasts express the muscle determination factor, MyoD, throughout the cell cycle in the absence of differentiation. Here we show that a mitogen-sensitive mechanism, involving the direct interaction between MyoD and cdk4, restricts myoblast differentiation to cells that have entered into the G0 phase of the cell cycle under mitogen withdrawal. Interaction between MyoD and cdk4 disrupts MyoD DNA-binding, muscle-specific gene activation and myogenic conversion of 10T1/2 cells independently of cyclin D1 and the CAK activation of cdk4. Forced induction of cyclin D1 in myotubes results in the cytoplasmic to nuclear translocation of cdk4. The specific MyoD-cdk4 interaction in dividing myoblasts, coupled with the cyclin D1-dependent nuclear targeting of cdk4, suggests a mitogen-sensitive mechanism whereby cyclin D1 can regulate MyoD function and the onset of myogenesis by controlling the cellular location of cdk4 rather than the phosphorylation status of MyoD.  (+info)

Cyclin D-CDK subunit arrangement is dependent on the availability of competing INK4 and p21 class inhibitors. (5/4016)

The D-type cyclins and their major kinase partners CDK4 and CDK6 regulate G0-G1-S progression by contributing to the phosphorylation and inactivation of the retinoblastoma gene product, pRB. Assembly of active cyclin D-CDK complexes in response to mitogenic signals is negatively regulated by INK4 family members. Here we show that although all four INK4 proteins associate with CDK4 and CDK6 in vitro, only p16(INK4a) can form stable, binary complexes with both CDK4 and CDK6 in proliferating cells. The other INK4 family members form stable complexes with CDK6 but associate only transiently with CDK4. Conversely, CDK4 stably associates with both p21(CIP1) and p27(KIP1) in cyclin-containing complexes, suggesting that CDK4 is in equilibrium between INK4 and p21(CIP1)- or p27(KIP1)-bound states. In agreement with this hypothesis, overexpression of p21(CIP1) in 293 cells, where CDK4 is bound to p16(INK4a), stimulates the formation of ternary cyclin D-CDK4-p21(CIP1) complexes. These data suggest that members of the p21 family of proteins promote the association of D-type cyclins with CDKs by counteracting the effects of INK4 molecules.  (+info)

Induced expression of p16(INK4a) inhibits both CDK4- and CDK2-associated kinase activity by reassortment of cyclin-CDK-inhibitor complexes. (6/4016)

To investigate the mode of action of the p16(INK4a) tumor suppressor protein, we have established U2-OS cells in which the expression of p16(INK4a) can be regulated by addition or removal of isopropyl-beta-D-thiogalactopyranoside. As expected, induction of p16(INK4a) results in a G1 cell cycle arrest by inhibiting phosphorylation of the retinoblastoma protein (pRb) by the cyclin-dependent kinases CDK4 and CDK6. However, induction of p16(INK4a) also causes marked inhibition of CDK2 activity. In the case of cyclin E-CDK2, this is brought about by reassortment of cyclin, CDK, and CDK-inhibitor complexes, particularly those involving p27(KIP1). Size fractionation of the cellular lysates reveals that a substantial proportion of CDK4 participates in active kinase complexes of around 200 kDa. Upon induction of p16(INK4a), this complex is partly dissociated, and the majority of CDK4 is found in lower-molecular-weight fractions consistent with the formation of a binary complex with p16(INK4a). Sequestration of CDK4 by p16(INK4a) allows cyclin D1 to associate increasingly with CDK2, without affecting its interactions with the CIP/KIP inhibitors. Thus, upon the induction of p16(INK4a), p27(KIP1) appears to switch its allegiance from CDK4 to CDK2, and the accompanying reassortment of components leads to the inhibition of cyclin E-CDK2 by p27(KIP1) and p21(CIP1). Significantly, p16(INK4a) itself does not appear to form higher-order complexes, and the overwhelming majority remains either free or forms binary associations with CDK4 and CDK6.  (+info)

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. (7/4016)

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by +info)

Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. (8/4016)

The response of the uterine epithelium to female sex steroid hormones provides an excellent model to study cell proliferation in vivo since both stimulation and inhibition of cell proliferation can be studied. Thus, when administered to ovariectomized adult mice 17beta-estradiol (E2) stimulates a synchronized wave of DNA synthesis and cell division in the epithelial cells, while pretreatment with progesterone (P4) completely inhibits this E2-induced cell proliferation. Using a simple method to isolate the uterine epithelium with high purity, we have shown that E2 treatment induces a relocalization of cyclin D1 and, to a lesser extent, cdk4 from the cytoplasm into the nucleus and results in the orderly activation of cyclin E- and cyclin A-cdk2 kinases and hyperphosphorylation of pRb and p107. P4 pretreatment did not alter overall levels of cyclin D1, cdk4, or cdk6 nor their associated kinase activities but instead inhibited the E2-induced nuclear localization of cyclin D1 to below the control level and, to a lesser extent, nuclear cdk4 levels, with a consequent inhibition of pRb and p107 phosphorylation. In addition, it abrogated E2-induced cyclin E-cdk2 activation by dephosphorylation of cdk2, followed by inhibition of cyclin A expression and consequently of cyclin A-cdk2 kinase activity and further inhibition of phosphorylation of pRb and p107. P4 is used therapeutically to oppose the effect of E2 during hormone replacement therapy and in the treatment of uterine adenocarcinoma. This study showing a novel mechanism of cell cycle inhibition by P4 may provide the basis for the development of new antiestrogens.  (+info)

Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
Uncontrolled cell proliferation is the hall mark of many cancers, and is typically manifested by a deregulation of the cell-division cycle. CDKs play critical roles in regulating cell cycle, apop- tosis and cell differentiation. AG-024322 is a multitargeted CDK inhibitor that has been shown to induce cancer cell apoptosis and de- monstrate significant antitumor activity in hu-man tumor xenograft models. This compound is under clinical development as an intravenous anticancer agent. AG-024322 exhibited moder-ate to high systemic clearance across preclini-cal species. In vitro metabolism in human liver microsomes and hepatocytes demonstrates that glucuronidation and oxidation represent the major metabolic pathways of AG-024322. The experiments of chemical inhibition and micro-somes containing individual CYP or UGT iso-forms revealed that CYP3A and UGT1A1 appear to predominantly mediate AG-024322 oxidation and glucuronidation, respectively. Formation kinetics of the two pathways in human liver mi-crosomes
Cyclin-Dependent Protein Kinase Inhibitor Set - Calbiochem The Cyclin-Dependent Protein Kinase Inhibitor Set controls the biological activity of Cyclin-Dependent Protein Kinase. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications. - Find MSDS or SDS, a COA, data sheets and more information.
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[65 Pages Report] Check for Discount on Cyclin-Dependent Kinase 2 (p33 Protein Kinase or cdc2-Related Protein Kinase or EC 2.7.11.22) - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, Cyclin-Dependent Kinase 2 (p33 Protein...
[51 Pages Report] Check for Discount on Cyclin-Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or CDK1 or EC 2.7.11.22) - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, Cyclin-Dependent Kinase 1 (p34 Protein...
CDKs (Cyclin-dependent kinases) are serine-threonine kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase.. There are around 20 Cyclin-dependent kinases (CDK1-20) known till date. CDK1, 4 and 5 are involved in cell cycle, and CDK 7, 8, 9 and 11 are associated with transcription.. CDK levels remain relatively constant throughout the cell cycle and most regulation is post-translational. Most knowledge of CDK structure and function is based on CDKs of S. pombe (Cdc2), S. ...
The cyclin-dependent kinase (CDK) inhibitor p27Kip1 has been shown to regulate cellular proliferation via inhibition of CDK activities. routine and g27Kip1 (hereafter g27) can regulate CDK actions.1-3 The p27 protein was originally known as an inhibitor of CDK activities for things containing CDK2 and shown to inhibit cyclin E and cyclin A activities which regulate G1 and S phase traverse.4-6 In addition to CDK inhibition, g27 provides other multifarious connections with cyclin N/cdk4 processes putatively.7 Since cellular amounts of g27 are elevated in response to high cell thickness, serum deprival, and TGF, it was hypothesized g27 brought cells into quiescence and held them in G0 through the inhibition of CDK actions.8 Numerous reviews have got characterized the control of p27 including the control of its transcription,9,10 translation,11,12 post-translational adjustments.7,13,14 cellular localization15-19 and balance.20-23 The regulations of its stability has a main role in adjusting mobile ...
Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) and adventitial fibroblasts play an important role in the pathobiology of vascular occlusive disease (eg, atherosclerosis, in-stent restenosis, transplant vasculopathy, and vessel bypass graft failure).1,2 Thus, understanding the molecular mechanisms that control hyperplastic growth and the locomotion of vascular cells should aid in the development of novel therapeutic strategies to reduce neointimal thickening.. Cell cycle progression is controlled by several cyclin-dependent kinases (CDKs) that associate with regulatory cyclins.3 Mitogenic stimuli activate CDK/cyclin holoenzymes, thus causing hyperphosphorylation of the retinoblastoma protein (pRb) and related pocket proteins from mid G1 to mitosis. CDK-dependent pRb hyperphosphorylation releases E2F transcription factors, thus contributing to the expression of several growth and cell cycle-regulatory genes with functional E2F-binding sites in their ...
Recombinant human CDKN1B protein, fused to His-tag at N-terminus, was expressed in E. coli and purified by using conventional chromatography. MW: 24.2 kDa.
The human cyclin-dependent kinase inhibitor 2A (CDKN2A) gene generates several transcript variants that differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported. One of these, cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) or p16INK4a, interacts with, and sequesters, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. Thus, p16-INK4a functions as a tumor suppressor in a variety of cells. Mutations in the CDKN2A gene are often found in many tumors. p16INK4a is also suggested to play a role in controlling cell proliferation and apoptosis during mammary gland development. p16-INK4a is also known as cyclin-dependent kinase 4 inhibitor A, CDK4 inhibitor p16-INK4, cell cycle negative regulator beta, multiple tumor suppressor 1 (MTS-1), ARF, MLM, p14, p16, p19, CMM2, INK4, INK4A, TP16, CDK4I, CDKN2, p14-ARF, p19-ARF, and p16-INK4.. ...
TY - JOUR. T1 - Systematic determination of human cyclin dependent kinase (CDK)-9 interactome identifies novel functions in RNA splicing mediated by the DEAD Box (DDX)-5/17 RNA helicases. AU - Yang, Jun. AU - Zhao, Yingxin. AU - Kalita, Mridul. AU - Li, Xueling. AU - Jamaluddin, Mohammad. AU - Tian, Bing. AU - Edeh, Chukwudi B.. AU - Wiktorowicz, John E.. AU - Kudlicki, Andrzej. AU - Brasier, Allan R.. PY - 2015/10/1. Y1 - 2015/10/1. N2 - Inducible transcriptional elongation is a rapid, stereotypic mechanism for activating immediate early immune defense genes by the epithelium in response to viral pathogens. Here, the recruitment of a multifunctional complex containing the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional elongation activating resting RNA polymerase engaged with innate immune response (IIR) genes. To identify additional functional activity of the CDK9 complex, we conducted immunoprecipitation (IP) enrichment-stable isotope labeling LC-MS/MS of the CDK9 ...
p21 is a potent cyclin-dependent kinase inhibitor. The p21 protein binds to and inhibits the activity of cyclin-CDK2 or -CDK1 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein me
In this report, we describe PD 0332991 as a potent and highly selective inhibitor of Cdk4 and Cdk6 and show that suppression of these enzymes in human tumor xenografts results in significant antitumor activity. Given that a major obstacle to establishing the usefulness of a Cdk4/6 inhibitor has been the difficulty in obtaining a molecule with complete specificity for these enzymes versus other Cdks and protein kinases, considerable effort was taken to establish the selectivity of this compound. PD 0332991 was tested against 39 individual serine, threonine, and tyrosine kinases, representing most of the primary protein kinase families (84). Other than Cdk4 and Cdk6, the compound had little or no activity against any of these enzymes. Based on the understood role of Cdk4/6 in cell cycle progression, a specific Cdk4/6 inhibitor is predicted to produce an exclusive G1 arrest. Consistent with this expectation, cells treated with concentrations of PD 0332991 as high as 200-fold above the IC50 for ...
Substituted guanines and pyrimidines were tested as inhibitors of cyclin B1/CDK1 and cyclin A3/CDK2 and soaked into crystals of monomeric CDK2. O6-Cyclohexylmethylguanine (NU2058) was a competitive inhibitor of CDK1 and CDK2 with respect to ATP (Ki values: CDK1, 5 +/- 1 microM; CDK2, 12 +/- 3 microM) and formed a triplet of hydrogen bonds (i.e., NH-9 to Glu 81, N-3 to Leu 83, and 2-NH2 to Leu 83). The triplet of hydrogen bonding and CDK inhibition was reproduced by 2,6-diamino-4-cyclohexylmethyloxy-5-nitrosopyrimidine (NU6027, Ki values: CDK1, 2.5 +/- 0.4 microM; CDK2, 1.3 +/- 0.2 microM). Against human tumor cells, NU2058 and NU6027 were growth inhibitory in vitro (mean GI50 values of 13 +/- 7 microM and 10 +/- 6 microM, respectively), with a pattern of sensitivity distinct from flavopiridol and olomoucine. These CDK inhibition and chemosensitivity data indicate that the distinct mode of binding of NU2058 and NU6027 has direct consequences for enzyme and cell growth inhibition.
Cancer develops due to an imbalance between cell proliferation and cell death. Various mechanisms of carcinogenesis as well as of novel anticancer agents that could be targeted for the treatment of cancer have been proposed by different studies. Among these, p21 is recognized as a potent cyclin-dependent kinase inhibitor that facilitates cell-cycle arrest by interacting with different stimuli such as p53, DNA repair process, CDK, E2F1, MYC, PCNA, STAT3 AP4, proteasomes, K1F, CDX2, and ER-α. p21 acts both as a tumor-suppressor gene and an inhibitor of apoptosis by interacting with various molecules and transition factors. In this review, we discuss the complex role of p21 in the development of cancer and as a target in its treatment. We conclude that, in the future, the tumor-suppressor activity of p21 should be the focus of a novel treatment strategies, which may lead to the devolvement of new and selective anti-cancer agents for the targeted therapy of cancers.. ...
Activation of the cyclin-dependent kinases to promote cell cycle progression requires their association with cyclins as well as phosphorylation of a threonine (residue 161 in human p34cdc2). This phosphorylation is carried out by CAK, the Cdk-activating kinase. We have purified and cloned CAK from S …
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7. Serine/Threonine Kinases (STKs), Cyclin-Dependent protein Kinase 7 (CDK7) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CDK7 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. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the ...
4216 Cell cycle related kinase (CCRK) is a newly identified cyclin-dependent kinase (CDK)-activating kinase (CAK). CCRK is indispensable for cell growth. Here we studied the expression profile of CCRK in colon tumor tissues by semi-quantitative RT-PCR. We found that 78% of the colon tumor tissues had an elevated level of CCRK expression, comparing with matched normal tissues. This result suggested that CCRK was involved in colon cancer tumorgenesis. Furthermore we found that CCRK was detectable in all cell lines derived from colon tumor, including p53 wild type cell lines (HCT116 and LoVo), and p53 mutant cell lines (colo205, DLD1, HT29, SW1116 and SW480). Suppression of CCRK by small interfering RNA (siRNA) significantly inhibited the proliferation of both LoVo and SW1116 cells. Flow cytometry analysis demonstrated that siCCRK caused a characteristic G1/S phase arrest, but no apoptosis, which is demonstrated by nuclear DAPI staining. In addition, we showed CCRK interacted with and activated ...
G1 cyclin-dependent kinase (Cdk)-triggered degradation of the S-phase Cdk inhibitor Sic1p has been implicated in the transition from G1 to S phase in the cell cycle of budding yeast. A multidimensional electrospray mass spectrometry technique was used to map G1 Cdk phosphorylation sites in Sic1p both in vitro and in vivo. A Sic1p mutant lacking three Cdk phosphorylation sites did not serve as a substrate for Cdc34p-dependent ubiquitination in vitro, was stable in vivo, and blocked DNA replication. Moreover, purified phosphoSic1p was ubiquitinated in cyclin-depleted G1 extract, indicating that a primary function of G1 cyclins is to tag Sic1p for destruction. These data suggest a molecular model of how phosphorylation and proteolysis cooperate to bring about the G1/S transition in budding yeast. ...
Coxon CR, Anscombe E, Harnor SJ, Martin MP, Carbain B, Golding BT, Hardcastle IR, Harlow LK, Korolchuk S, Matheson CJ, Newell DR, Noble ME, Sivaprakasam M, Tudhope SJ, Turner DM, Wang LZ, Wedge SR, Wong C, Griffin RJ, Endicott JA, Cano C. Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines. J Med Chem. 2017 03 09; 60(5):1746-1767 ...
Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase. Serine/Threonine Kinases (STKs), Plant B-type Cyclin-Dependent protein Kinase (CdkB) subfamily, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CdkB 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. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata ...
Phosphorylation of Sic1, a Cyclin-dependent Kinase (Cdk) Inhibitor, by Cdk Including Pho85 Kinase Is Required for Its Prompt Degradation: In the yeast Saccharom
Although most efforts to develop antagonists of CDK function have focused on identifying and optimizing ATP-competitive CDK inhibitors, a number of studies have been published in which new, creative strategies have been used. Most of these approaches focus on CDK2 inhibition. This is in part due to the fact that X-ray crystal structures of CDK2 and the cyclin A/CDK2 complex have been available longer than similar data for other CDK and cyclin/CDK complexes. A crystal structure of cyclin A/CDK2 in complex with ATP and a substrate peptide (Brown et al., 1999) (Fig. 3A) shows ATP bound in a cleft formed on one side by the GEGTYG nucleotide-binding motif (red- and blue-colored residues). The peptide substrate is bound in a cleft adjacent to the ATP binding site and in close apposition to ATP. Interestingly, binding of the endogenous CDK inhibitor p27 to cyclin A/CDK2 causes large-scale structural changes to the cyclin A/CDK2 complex (Fig. 3B) (Russo et al., 1996). p27 inserts itself into the ATP ...
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Cow (Bovine). Source: Yeast. Order product ABIN1616360.
Recombinant Cyclin-Dependent Kinase 10 (CDK10) Protein (His tag). Species: Human. Source: Insect Cells. Order product ABIN3091398.
https://astx.com/wp-content/uploads/2019/11/logo_white.png 0 0 webadmin https://astx.com/wp-content/uploads/2019/11/logo_white.png webadmin2010-11-29 12:06:482016-11-29 12:06:57Cho et al. 4-(Pyrazol-4-yl)-pyrimidines as Selective Inhibitors of Cyclin-Dependent Kinase 4/6. Journal of Medicinal Chemistry 53, no. 22 2010: 7938-7957. DOI: 10.1021/jm100571n. ...
The conversation the turned to patient eligibility and the panel agreed that it was prudent to offer the best possible treatment first to patients, where possible, due to the proven response rates seen with CDK 4/6 inhibitors. This point was of particular interest to Dr Beresford as ribociclib and palbocilcib are not approved for 2nd line use in the U.K., and therefore will not be an option for those who are treated with hormone therapy, for example, as an initial option. The panel also reiterated the importance of considering CDK 4/6 inhibitors as a 1st line option to avoid the over use of chemotherapy; a strategy that was backed up by the PALOMA-1 study that showed treatment with a CDK 4/6 inhibitor delayed the time until a patient received subsequent chemotherapy treatment ...
Synonyms: Regulation of Nuclear Pre-MRNA Domain Containing 1A, RPRD1A, P15RS, Cyclin-Dependent Kinase 2B-Inhibitor-Related Protein, Cyclin-Dependent Kinase Inhibitor 2B-Related Protein (P15INK4B-Related Protein), P15INK4B-Related Protein, HsT3101, Regulation of Nuclear Pre-MRNA Domain-Containing Protein 1A, Cyclin-Dependent Kinase Inhibitor 2B-Related Protein, FLJ10656.. ...
Professor Nadia Harbeck Chairs an expert discussion on the latest in CDK inhibition in breast cancer and what this means for patients for ecancer at the 40th
Disruption of the cyclin-dependent kinase-inhibitory domain of p27 enhances growth of mice. Growth is attributed to an increase in cell number, due to increased cell proliferation, most obviously in tissues that ordinarily express p27 at the highest levels. Disruption of p27 function leads to nodula …
p53 induction and cell cycle arrest occur following DNA damage, possibly to allow repair prior to replication. p21WAF1/CIP1, a cyclin-cyclin-dependent kinase inhibitor and proliferating cell nuclear antigen-interacting protein, is induced by p53 and mediates the cell cycle arrest. To investigate a role for p21 in DNA repair in vivo, we studied the expression of in vitro damaged reporter DNA transfected into p21 +/+ or -/- HCT116 human colon cancer cells. Introduction of UV-damaged or cis-platinum-damaged cytomegalovirus-driven β-galactosidase reporter DNA into tumor cells revealed a significant decrease (2-5-fold) in reporter expression in p21 -/- versus +/+ cells. In the absence of DNA damage, there was a significant increase (2-3-fold) in the number of 6-TG-resistant colonies derived from p21 -/- versus +/+ cells. Reintroduction of wild-type p21, but not a p21 C-terminal truncation mutant which lacks the proliferating cell nuclear antigen interaction domain, stimulated (2-3-fold) the repair ...
CDKN2A - CDKN2A (untagged)-Human cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A), transcript variant 4 available for purchase from OriGene - Your Gene Company.
Lenti ORF clone of Human cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) (CDKN2A), transcript variant 1, mGFP tagged
p27/Kip1 antibody to detect human cyclin-dependent kinase inhibitor 1. Validated on up to 12 cell lysates for western blotting. Try a trial size today.
Principal Investigator:ANDO Shoji, Project Period (FY):1996 - 1997, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Bioorganic chemistry
Dysregulation of cell cycle machinery is implicated in a number of neuronal death contexts, including stroke. Increasing evidence suggests that cyclin-dependent kinases (Cdks) are inappropriately activated in mature neurons under ischemic stress conditions. We previously demonstrated a functional role for cyclin D1/Cdk4/pRb pathway in delayed neuronal death induced by ischemia. However, the molecular signal(s) leading to cyclin D/Cdk4/pRb activation following ischemic insult is presently not clear. Here, we investigate the cell division cycle 25 (Cdc25) dual specificity phosphatases as potential upstream regulators of ischemic neuronal death and Cdk4 activation. We show that a pharmacologic inhibitor of Cdc25 family members (A, B & C) protects mouse primary neurons from hypoxia-induced delayed death. The major contributor to the death process appears to be Cdc25A. shRNA mediated knockdown of Cdc25A protects neurons in a delayed model of hypoxia-induced death in vitro. Similar results were ...
Cyclin-dependent kinases (CDKs) contribute to the cancer hallmarks of uncontrolled proliferation and increased survival. As a result, over the last two decades substantial efforts have been directed towards identification and development of pharmaceutical CDK inhibitors. Insights into the biological consequences of CDK inhibition in specific tumor types have led to the successful development of CDK4/6 inhibitors as treatments for certain types of breast cancer. More recently, a new generation of pharmaceutical inhibitors of CDK enzymes that regulate the transcription of key oncogenic and pro-survival proteins, including CDK9, have entered clinical development. Here, we provide the first disclosure of the chemical structure of fadraciclib (CYC065), a CDK inhibitor and clinical candidate designed by further optimization from the aminopurine scaffold of seliciclib. We describe its synthesis and mechanistic characterization. Fadraciclib exhibits improved potency and selectivity for CDK2 and CDK9 ...
Clone REA756 recognizes the human CD20L, an intracytoplasmic membrane protein, which is also known as Htm4 or MS4A3. It is present specifically in hematopoietic cells and tissues. CD20L functions as a hematopoietic modulator for the G1-S cell cycle transition. It binds to cyclin-dependent kinase inhibitor 3 (CDKN3/KAP) and modulates the level of phosphorylation of cyclin-dependent kinase 2 (CDK2). Additional information: Clone REA756 displays negligible binding to Fc receptors. - Österreich
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1OIT: Imidazo[1,2-A]Pyridines: A Potent and Selective Class of Cyclin-Dependent Kinase Inhibitors Identified Through Structure-Based Hybridisation
We manufacture and offer the CCRK Antibody (N-Term)(Ascites) for signal transduction and crown antibody research areas. Order the CDK20 antibody from Abgent!
Looking for online definition of cyclin-dependent kinase 15 in the Medical Dictionary? cyclin-dependent kinase 15 explanation free. What is cyclin-dependent kinase 15? Meaning of cyclin-dependent kinase 15 medical term. What does cyclin-dependent kinase 15 mean?
Cyclin/cyclin-dependent kinase (CDK) complexes are critical regulators of cellular proliferation. A complex network of regulatory mechanisms has evolved to control their activity, including activating and inactivating phosphorylation of the catalytic CDK subunit and inhibition through specific regulatory proteins. Primate herpesviruses, including the oncogenic Kaposi sarcoma herpesvirus, encode cyclin D homologues. Viral cyclins have diverged from their cellular progenitor in that they elicit holoenzyme activity independent of activating phosphorylation by the CDK-activating kinase and resistant to inhibition by CDK inhibitors. Using sequence comparison and site-directed mutagenesis, we performed molecular analysis of the cellular cyclin D and the Kaposi sarcoma herpesvirus-cyclin to delineate the molecular mechanisms behind their different behavior. This provides evidence that a surface recognized for its involvement in the docking of CIP/KIP inhibitors is required and sufficient to modulate ...
The molecular mechanisms underlying erlotinib resistance in breast cancer have not been well defined. In our screening of breast cancer cell lines, down-regulation of CDK2 after treatment with erlotinib showed association with erlotinib sensitivity. Moreover, our study provides that erlotinib sensitivity is causally linked with CDK2 activity, indicating that erlotinib sensitivity depends, at least in part, on CDK2 activity. Some reports have indicated that the growth-inhibitory effect induced by EGFR-TKIs in sensitive cell lines depends mainly on G1 cell cycle arrest (1, 7, 11, 13); others have shown CDK2 activity to be down-regulated after treatment with an EGFR-TKI (12, 13). However, this is the first report establishing cause and effect relationship between erlotinib sensitivity and CDK2 activity.. The erlotinib sensitivity of breast cancer cell lines has clinical relevance for several reasons. The limited clinical activity of EGFR-TKIs in breast cancer was also echoed by the findings of this ...
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The EL2 gene of rice (Oryza sativa), previously classified as early response gene against the potent biotic elicitor N-acetylchitoheptaose and encoding a short polypeptide with unknown function, was identified as a novel cell cycle regulatory gene related to the recently reported SIAMESE (SIM) gene of Arabidopsis thaliana. Iterative two-hybrid screens, in vitro pull-down assays, and fluorescence resonance energy transfer analyses showed that Orysa; EL2 binds the cyclin-dependent kinase (CDK) CDKA1;1 and D-type cyclins. No interaction was observed with the plant-specific B-type CDKs. The amino acid motif ELERFL was identified to be essential for cyclin, but not for CDK binding. Orysa;EL2 impaired the ability of Orysa; CYCD5;3 to complement a budding yeast (Saccharomyces cerevisiae) triple CLN mutant, whereas recombinant protein inhibited CDK activity in vitro. Moreover, Orysa;EL2 was able to rescue the multicellular trichome phenotype of sim mutants of Arabidopsis, unequivocally demonstrating that Orysa
The cortactin oncoprotein is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC), often due to amplification of the encoding gene (CTTN). While cortactin overexpression enhances invasive potential, recent research indicates that it also promotes cell proliferation, but how cortactin regulates the cell cycle machinery is unclear. In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. Cortactin regulated expression of p21(WAF1/Cip1) and p27(Kip1) at the transcriptional and posttranscriptional levels, respectively. The direct roles of p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) ...
TY - JOUR. T1 - Molecular cloning of a cyclin-like protein associated with cyclin-dependent kinase 3 (cdk 3) in vivo. AU - Matsuoka, Masaaki. AU - Matsuura, Yoshiharu. AU - Semba, Kentaro. AU - Nishimoto, Ikuo. PY - 2000/7/5. Y1 - 2000/7/5. N2 - cdk3 has been considered to be rate-limiting for cell cycle progression of mammalian cells while its precise function remains to be elucidated, To assess cdk3 function, a cDNA coding for a cyclin-like protein (designated as ik3-1 from an interactor-1 with cdk3) was isolated with the yeast two-hybrid system using a cyclin-dependent kinase 3 (cdk3) cDNA as bait. p70(ik3-1) (a 70-kDa protein designated as p70(ik3-1)) seems to belong to the cyclin family as its C-terminal domain composed of 124 amino acids resembles the highly conserved cyclin box. Coimmunoprecipitation indicated that p70(ik3-1) binds to p35(cdk3) in vivo. The ik3-1 gene may belong to a multigene family and is highly conserved during evolution. mRNA expression of ik3-1 was low in the early ...
In this paper, we report that (+)-preussin, a pyrrolidinol alkaloid originally identified as an antifungal agent, has growth-inhibitory and cytotoxic effects on human cancer cells. Preussin was found to be a potent inhibitor of cyclin E kinase (CDK2-cyclin E) in vitro (50% inhibitory concentration; approximately 500 nM) and to inhibit cell cycle progression into S phase. In agreement with these findings, the level of the cyclin-dependent kinase inhibitor p27(KIP-1) is increased in response to preussin treatment while the expression of both cyclin A and the transcription factor E2F-1 is down-regulated. Preussin also induces programmed cell death (apoptosis), which requires caspase activation and involves the release of cytochrome c from mitochondria. This induction of apoptosis is not blocked by high levels of Bcl-2, which usually confers resistance to chemotherapeutic agents. Taken together, our data indicate that preussin could be a promising lead compound for the development of a new class of potent
Cyclin-dependent kinases (CDKs) are a family of sugar kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The consensus sequence for the phosphorylation site in the amino acid sequence of a CDK substrate is [S/T*]PX[K/R], where S/T* is the ...
Supinoxin, also known as RX-5902, is orally bioavailable small molecule inhibitor of phosphorylated-p68 RNA helicase (P-p68), with potential anti-proliferative and antineoplastic activity. Upon oral administration, P-p68 inhibitor RX-5902 may both inhibit the activity of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein and facilitate the induction of cyclin-dependent kinase inhibitor 1 (p21). This may prevent G2/M cell cycle progression and lead to growth inhibition in tumor cells. P-p68 is overexpressed in various types of solid tumors but absent in normal tissues, and plays a role in tumor progression and metastasis. p21 is a potent cyclin-dependent kinase inhibitor which regulates cell cycle progression and mediates both growth arrest and cellular senescence. (Last updated: 6/16/2015)
CDC25A plays a role in the unperturbed cell cycle (Ben-Yehoyada et al., 2007); to address the concern that the CDC25A siRNA was slowing down replication, which would affect the result, we pulsed cells with BrdU after 48 h of CDC25A siRNA transfection and chased the cells for 8 h. Flow cytometric analysis revealed that the progression through S phase at these time points was largely unaffected by the lower cellular concentration of CDC25A (Fig. S3 E). Thus, repression of DNA damage after CDC25A depletion is not caused by markedly slowed progression through S phase or G1-phase arrest.. Finally, we asked whether CDC25A accumulation could be an important determinant of the proliferative capability of cells depleted for CHK1 because coknockdown of CDC25A with CHK1 abolished the majority of DNA damage. Importantly, TIG-3-tert cells depleted for CHK1 proliferated very poorly, whereas this phenotype was partly rescued by codepletion of CDC25A. In fact, cells depleted for both CDC25A and CHK1 ...
TY - JOUR. T1 - SU9516, a cyclin-dependent kinase 2 inhibitor, promotes accumulation of high molecular weight E2F complexes in human colon carcinoma cells. AU - Yu, Bo. AU - Lane, Maureen E.. AU - Wadler, Scott. PY - 2002/10/1. Y1 - 2002/10/1. N2 - The E2F family plays a critical role in the expression of genes required for entry into and progression through S phase. E2F-mediated transcription is repressed by the tumor suppressor retinoblastoma protein (pRb), which results in sequestration of E2F in a multiprotein complex that includes pRb. Derepression of E2F results from a series of complex phosphorylation events mediated by cyclin D/cdk4 and cyclin E/cdk2. We have employed a novel 3-substituted indolinone compound, 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), which selectively inhibits cdk2 activity (Lane et al., Cancer Res 2001;61:6170-7) to investigate these events. Electrophoretic mobility gel shift assays were performed on SU9516-treated and ...
p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. Here, we recorded CA1 pyramidal cell activity in freely behaving p35 cKO and control mice and found that place cells in the mutant mice have elevated firing rates and impaired spatial coding, accompanied by changes in the temporal organization of spiking both during exploration and rest. These data shed light on the role of p35 in maintaining cellular and network excitability and provide a physiological correlate of the spatial learning deficits in these mice.
Background Over the last decade a number of species, from farm animals to rodents, have been cloned using somatic cell nuclear transfer technology (SCNT). This technique has the potential to revolutionize the way that genetically modified animals are made. In its current state, the process of SCNT is very inefficient (|5% success rate), with several technical and biological hurdles hindering development. Yet, SCNT provides investigators with powerful advantages over other approaches, such as allowing for prescreening for the desired level of transgene expression and eliminating the excess production of undesirable wild-type animals. The rat plays a significant role in biomedical research, but SCNT has been problematic for this species. In this study, we address one aspect of the problem by evaluating methods of activation in artificially constructed rat embryos. Principal Findings We demonstrate that treatment with a calcium ionophore (ionomycin) combined with a variety of cyclin-dependent kinase
The cyclin-dependent kinases (Cdks) regulate many cellular processes, including the cell cycle, neuronal development, transcription, and posttranscriptional processing. To perform their functions, Cdks bind to specific cyclin subunits to form a functional and active cyclin/Cdk complex. This review is focused on Cyclin K, which was originally considered an alternative subunit of Cdk9, and on its newly identified partners, Cdk12 and Cdk13. We briefly summarize research devoted to each of these proteins. We also discuss the proteins functions in the regulation of gene expression via the phosphorylation of serine 2 in the C-terminal domain of RNA polymerase II, contributions to the maintenance of genome stability, and roles in the onset of human disease and embryo development.
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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. Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. CDKs regulate the cells progression through the phases of the cell cycle by modulating the activity of key substrates. Downstream targets of CDKs include transcription factor E2F and its regulator Rb. Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. 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. Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. In response to DNA ...
Cyclin D-CDK4/6 are the first CDK complexes to be activated in G1 phase in response to oncogenic pathways. The specific CDK4/6 inhibitor PD0332991 (Palbociclib) was recently approved by the FDA to treat advanced ER+ breast tumors. Unfortunately, reliable predictive tools are lacking to identify potentially responsive or insensitive tumors. We have shown that the activating T172 phosphorylation of CDK4 is the central rate-limiting event that initiates the cell cycle decision and signals the presence of active CDK4. Here, we found that, in breast cancer cell lines, the CDK4 T172 phosphorylation best correlates with the sensitivity to PD0332991. Moreover, the modification profile of CDK4 differs among breast tumors and it associates with their subtypes and risk. A gene expression signature faithfully predicted CDK4 modification profiles in tumors and cell lines. This surrogate biomarker identifies tumors that are unlikely to respond to CDK4/6 inhibitors and could allow extending the indication of the drug
Cyclin-dependent kinase 4 (CDK4) is a member of cyclin-dependent kinase family which regulates G1 to S cell cycle transition. CDK4 activity is increased in many tumor types. Here, we report a...
Cyclin Dependent Kinase 1 (p34 Protein Kinase or Cell Division Protein Kinase 1 or Cell Division Control Protein 2 Homolog or CDK1 or EC 2.7.11.22 or EC 2.7.11.23) - Pipeline Review, H2 2017 Size and Share Published in 2017-08-29 Available for US$ 3500 at Researchmoz.us
Vol 7: PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis.. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
A novel synthetic retinoid, 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437), is a selective ligand of the RARgamma nuclear receptor. We examined the in vitro effects of CD437 and found that CD437 induces S phase arrest within 24 to 48 h, followed by cell death, in the p53-negative Hep3B and the p53-positive HepG2 human hepatoma cell lines. Based on observations of cellular and nuclear fragmentation, chromatin condensation, and DNA fragmentation, the CD437-mediated cell-killing effect appears to be due to apoptosis. On morphological examination, a number of CD437-treated cells were found to have increased 5- to 10-fold in size and persisted as single giant cells without cell division, while the remainder underwent nuclear division (multiple nuclei) but were unable to complete cytokinesis, and finally all died by apoptosis. In HepG2 cells that possessed wild-type p53, CD437-induced S phase arrest and apoptosis were accompanied by the up-regulation of cyclin A, cyclin B, p53, p21
Centrosome Duplication And Separation Are Linked Inextricably To Certain Cell Cycle Events, In Particular Activation Of Cyclin-dependent Kinases (CDKs). However, Relatively Few CDK Targets Driving These Events Have Been Uncovered. Here, We Have Performed
DESCRIPTION (provided by applicant): This Phase II SBIR project is aimed at developing a novel type of drugs, termed SNX9-class compounds, with a unique combination of two anticancer activities. The first is a selective antiproliferative effect on tumor cells relative to normal cells. The second is the inhibition of chemotherapy- or radiation-induced expression of multiple genes encoding secreted tumor-supporting factors with mitogenic, antiapoptotic and angiogenic activities; as a result, SNX9-class compounds potentiate the induction of apoptosis by conventional chemotherapeutic drugs. Studies conducted during Phase I of this project showed that both activities of SNX9- class compounds are due to their ability to inhibit CDK3. This understudied member of the cyclin-dependent kinase (CDK) family is apparently unneeded by normal cells, based on its very low expression in normal human tissues and spontaneous germline inactivation in laboratory mice. However, CDK3 is overexpressed in different ...
Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1-independent manner.
For example, in frogs, cyclin dependent protein kinase 2 (CDK2) binds to cyclin B to form an active kinase which phosphorylates a prereplication complex initiating S phase and mitosis. Cyclin B, a 45Kd protein, accumulates to high levels just before S phase. Its concentration drops sharply at the end of mitosis. The kinase, a 34 Kd protein, is encoded by the CDC2 gene (for cell division cycle gene). A homologous gene exists in humans - the CDK2 gene (cyclin dependent kinase 2) - and controls entry in S phase. These kinases can be considered heterodimers with a kinase catalytic subunit and a cyclin regulatory subunit. In animal cells, there are at least ten different cyclins (A, B, .....) and at least eight different cyclin-dependent kinases (CDK1-8). Another Look at Neurotransmission and Ion Channels. You may have noticed above that some signaling molecules, whose effects are regulated by kinases (b-adrenergic and some olfactory signals by PKA and acetylcholine by PKC for example), are ...
View and buy high purity Purvalanol B from Tocris Bioscience. Selective cdk inhibitor; potently inhibits cdk1, cdk2 and cdk5. Cited in 3 publications.
Mcl-1 (myeloid cell leukaemia-1) is a Bcl-2 family member with short-term pro-survival functions but whose other functions, demonstrated by embryonic lethality of knockout mice, do not involve apoptosis. In the present study, we show a cell-cycle-regulatory role of Mcl-1 involving a shortened form of the Mcl-1 polypeptide, primarily localized to the nucleus, which we call snMcl-1. snMcl-1 interacts with the cell-cycle-regulatory protein Cdk1 (cyclin-dependent kinase 1; also known as cdc2) in the nucleus, and Cdk1 bound to snMcl-1 was found to have a lower kinase activity. The interaction with Cdk1 occurs in the absence of its cyclin partners and is enhanced on treatment of cells with G2/M blocking agents, but not by G1/S blocking. The snMcl-1 polypeptide is present during S and G2 phases and is negligible in G1. Overexpression of human Mcl-1 in a murine myeloid progenitor cell line resulted in a lower rate of proliferation. Furthermore, Mcl-1-overexpressing cells had lower total Cdk1 kinase ...
In early S-phase, Clb5 and Clb6 initiate replication, and Clb5 simultaneously inhibits rereplication, probably acting through phosphorylation of Mcm and the Orc complex, since both are likely to be favored phosphorylation targets of Clb5 (Wilmes et al. 2004; Archambault et al. 2005a; Loog and Morgan 2005).. A clb1 clb2(ts) clb3 clb4 strain (Amon et al. 1993) additionally containing ORC6-ps,rxl GAL-CDC6ΔNT(m) showed G2 accumulation and no rereplication at a nonpermissive temperature in galactose (supplemental Figure S2 at http://www.genetics.org/supplemental/). In this strain, replication is driven exclusively by Clb5,6 (Schwob et al. 1994). This supports the hypothesis that S-phase cyclins, in addition to targeting Orc6, can regulate other rereplication-limiting substrates independently of Orc6 binding or Orc6 phosphorylation, such as the Mcm complex (Loog and Morgan 2005). In the converse situation, when initiation is driven in the absence of CLB5,6 and all replication is under control of ...
Plays a key role in the control of the eukaryotic cell cycle. It is required in higher cells for entry into S-phase and mitosis. p34 is a component of the kinase complex that phosphorylates the repetitive C-terminus of RNA polymerase II.
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CGP74514A is a CDK1 inhibitor with potential anticancer activity. In U937 cells, CGP74514A - induced apoptosis (5 microM) became apparent within 4 hr and approached 100% by 24 hr. The pan- caspase inhibitor Boc-fmk and the caspase-8 inhibitor lETD-fmk opposed CGP74514A -induced caspase-9 activation and PARP degradation, but not cytochrome c or Smac/DIABLO release. CGP74514A -mediated apoptosis was substantially blocked by ectopic expression of full-length Bel- 2, a loop-deleted mutant Bcl-2, and Bcl-x(L). CGP74514A treatment (5 microM; 18 hr) resulted in increased p21(CIP1) expression, p27(KIP1) degradation, diminished E2F1 expression, and dephosphorylation of p34(CDC2). It also induced early (i.e., within 2 hr) inhibition of CDK1 activity and dephosphorylation of pRb, followed by pRb degradation, but did not block pRb phosphorylation at CDK2- and CDK4- specific sites. These findings indicate that the selective CDK1 inhibitor, CGP74514A , induces complex changes in cell cycle-related proteins in human
To achieve faithful replication of the genome once in each cell cycle, reinitiation of S phase is prevented in G(2) and origins are restricted from refiring within S phase. We have investigated the block to rereplication during G(2) in fission yeast. The DNA synthesis that occurs when G(2)/M cyclin-dependent kinase (CDK) activity is depleted has been assumed to be repeated rounds of S phase without mitosis, but this has not been demonstrated to be the case. We show here that on G(2)/M CDK depletion in G(2), repeated S phases are induced, which are correlated with normal G(1)/S transcription and attainment of doublings in cell size. Mostly normal mitotic S-phase origins are utilized, although at different efficiencies, and replication is essentially equal across the genome. We conclude that CDK inhibits reinitiation of S phase during G(2), and if G(2)/M CDK is depleted, replication results from induction of a largely normal S-phase program with only small differences in origin usage and efficiency ...
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Cell proliferation is an important determinant of plant growth and development. In addition, modulation of cell-division rate is an important mechanism of plant plasticity and is key in adapting of plants to environmental conditions. One of the greatest challenges in understanding the cell cycle of flowering plants is the large families of CDKs and cyclins that have the potential to form many different complexes. However, it is largely unclear which complexes are active. In addition, there are many CDK- and cyclin-related proteins whose biological role is still unclear, i.e. whether they have indeed enzymatic activity. Thus, a biochemical characterization of these proteins is of key importance for the understanding of their function. Here we present a straightforward system to systematically express and purify active CDK-cyclin complexes from E. coli extracts. Our method relies on the concomitant production of a CDK activating kinase, which catalyzes the T-loop phosphorylation necessary for kinase
Cell proliferation is an important determinant of plant growth and development. In addition, modulation of cell-division rate is an important mechanism of plant plasticity and is key in adapting of plants to environmental conditions. One of the greatest challenges in understanding the cell cycle of flowering plants is the large families of CDKs and cyclins that have the potential to form many different complexes. However, it is largely unclear which complexes are active. In addition, there are many CDK- and cyclin-related proteins whose biological role is still unclear, i.e. whether they have indeed enzymatic activity. Thus, a biochemical characterization of these proteins is of key importance for the understanding of their function. Here we present a straightforward system to systematically express and purify active CDK-cyclin complexes from E. coli extracts. Our method relies on the concomitant production of a CDK activating kinase, which catalyzes the T-loop phosphorylation necessary for kinase
CDK2 is a catalytic subunit of the cyclin-dependent protein kinase complex, and is essential for cell cycle G1S phase transition. This protein is coexpressed and copurified with CyclinA.
Alsterpaullone, cyclin-dependent kinase (CDK) and GSK-3beta inhibitor (CAS 237430-03-4), with |96% purity. Join researchers using our high quality biochemicals.
Complete information for CDKN2D gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 2D, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for CDKN2B gene (Protein Coding), Cyclin Dependent Kinase Inhibitor 2B, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional machinery, where it phosphorylates the C-terminal domain (CTD) of RNAP polymerase II (RNAPII). Because many tumor types are critically dependent on transcription for maintenance of their oncogenic state, pharmacological modulation of CDK7 kinase activity is considered as an approach to treat cancer. Multiple series of CDK7 inhibitors were identified by iterative medicinal chemistry efforts and SAR based approach. Early compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumor activity. We have identified compounds from two distinct chemical series that are highly potent in inhibiting CDK7 in biochemical assays. These inhibitors demonstrate time-dependent inhibition of CDK7 indicating covalent nature of binding. The compounds showed potent anti-proliferative activity in cell lines derived from ...
The researchers examined a protein called cyclin-dependent kinase 2 (CDK2), which works as a quality control inspector. As normal cells divide, they pause in the replication process when they find inaccurate genetic code embedded in their DNA. The health and well-being of offspring cells depends on accurate genetic code transfer from one generation of cells to the next. The Mayo researchers showed that when errors in genes are irreparable, CDK2 modifies another cellular protein -- FOXO1 -- to send a signal that results in the death of the cell. This protein-to-protein relationship invites targeted drug intervention to control unregulated growth of cancer cells ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
Cyclin-dependent kinase 5[edit]. Cyclin-dependent kinase 5 (CDK5) is a kinase that has been previously hypothesized to ... A protein called kinase p38γ phosphorylates tau at the threonine-205 amino acid. The activity of this gamma kinase enzyme is ... It was found that the degree of tau pathology was dependent on time and the level of gene expression.[3] Groups receiving a ... As well as lead encephalopathy, tuberous sclerosis, Pantothenate kinase-associated neurodegeneration, and lipofuscinosis[28] ...
He holds a US and international patent on Activators of Cyclin-Dependent Kinases (ACDK) and has mentored many doctoral scholars ... "Activators of cyclin-dependent kinases". Google Patents. Retrieved 20 December 2017. "PhD Thesis" (PDF). ShodhGanga. 2011. ...
... is a family of cyclin-dependent kinase inhibitors (CKIs). The members of this family (p16INK4a, p15INK4b, p18INK4c, ... Ortega S, Malumbres M, Barbacid M (March 2002). "Cyclin D-dependent kinases, INK4 inhibitors and cancer". Biochimica et ... cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4))". Atlas of genetics and cytogenetics in oncology and haematology. ... Enforced expression of INK4 proteins can lead to G1 arrest by promoting redistribution of Cip/Kip proteins and blocking cyclin ...
... has been shown to interact with: C-jun, CREB-binding protein, CSRP3, Cyclin-dependent kinase 4, Cyclin-dependent kinase ... MyoD is inhibited by cyclin dependent kinases (CDKs). CDKs are in turn inhibited by p21. Thus MyoD enhances its own activity in ... Both MyoD and pRb are necessary for the repression of cyclin D1, but rather than acting directly on cyclin D1, they act on Fra- ... This is done through regulation of the Cyclin, Cyclin D1. Cell cycle arrest (in which myoblasts would indicate the conclusion ...
Shi J, Nelson MA (2005). "The cyclin-dependent kinase 11 interacts with NOT2". Biochem. Biophys. Res. Commun. 334 (4): 1310-6. ...
CDK7 is a cyclin-dependent kinase shown to be not easily classified. CDK7 is both a CDK-activating kinase (CAK) and a component ... "CAK-cyclin-dependent activating kinase: a key kinase in cell cycle control and a target for drugs?" Cell cycle 4.4 (2005): 565- ... 1995). Inhibition of cyclin-dependent kinases by p21. Mol. Biol. Cell 6, 387-400 Lolli, G., Lowe, E. D., Brown, N. R. and ... Mol Biol Cell 1993, 4:79-92 Matsuoka M, Kate JY, Fisher RP, Mor of cyclin-dependent kinase 4 (cdk4 by B mouse M015-an ...
"Cyclin Dependent Kinases and Cell Cycle Control" (PDF). nobelprize.org. Retrieved 4 June 2015. "Robert G. Edwards - ...
p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins ... "CDKN2A cyclin dependent kinase inhibitor 2A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2016-10-11. ... CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9, band p21.3. ... "CDKN2A - Cyclin-dependent kinase inhibitor 2A - Homo sapiens (Human) - CDKN2A gene & protein". www.uniprot.org. Retrieved 2016- ...
Dutta discovered how the cell cycle factor p21 interacts with and inhibits cyclin-dependent kinases and PCNA, identifying the ... Takeda, DY; Wohlschlegel, JA; Dutta, A (19 January 2001). "A bipartite substrate recognition motif for cyclin-dependent kinases ... Vaziri, C; Saxena, S; Jeon, Y; Lee, C; Murata, K; Machida, Y; Wagle, N; Hwang, DS; Dutta, A (April 2003). "A p53-dependent ... Chen, J; Saha, P; Kornbluth, S; Dynlacht, BD; Dutta, A (September 1996). "Cyclin-binding motifs are essential for the function ...
Jain SK, Bharate SB, Vishwakarma RA (2012). "Cyclin-dependent kinase inhibition by flavoalkaloids". Mini Rev Med Chem. 12 (7): ... Bose P, Simmons GL, Grant S (2013). "Cyclin-dependent kinase inhibitor therapy for hematologic malignancies". Expert Opin ... One example is alvocidib, a potent CDK9 kinase inhibitor that is being developed for the treatment of chronic lymphocytic ...
Nguyen, Van Q.; Co, Carl; Li, Joachim J. (2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple ... the pre-replication complex only occurs during late M phase and early G1 phase of the cell cycle when cyclin-dependent kinase ( ... The singular archaeal ORC protein recognizes the AT-rich tracts and binds DNA in an ATP-dependent fashion. Eukaryotes typically ... "DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1". EMBO Reports. 7 (11): 1134- ...
"Distinct roles for cyclin-dependent kinases in cell cycle control." Science 262.5142 (1993): 2050-2054. Harlow, E. D., et al. " ... "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5." (1994): 419-423. Meyerson, Matthew, et al. "A family ... Tsai, L (1994). "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature. 371: 419-23. doi:10.1038/ ... van den Heuvel, S (1993). "Distinct roles for cyclin-dependent kinases in cell cycle control". Science. 262: 2050-4. doi: ...
Cyclins are molecules that manage the timing of cell cycle events. Cyclin dependent kinases pair up with cyclins to become ... These include INKS for inhibitors of kinase, KIPS for kinase inhibitors and CKIPS for cyclin dependent kinases inhibitors. ... Cyclins are named because they are created or destroyed at predetermined points within the cell cycle. Kinase inhibitors add ... Kinase inhibitors are grouped into classes and are assigned not very descriptive acronyms. ...
... "ik3-1/Cables is a substrate for cyclin-dependent kinase 3 (cdk 3)". European Journal of Biochemistry / FEBS. 268 (23): 6076-82 ... "Specific regulation of E2F family members by cyclin-dependent kinases". Molecular and Cellular Biology. 17 (7): 3867-75. doi: ... He Y, Cress WD (Jun 2002). "E2F-3B is a physiological target of cyclin A". The Journal of Biological Chemistry. 277 (26): 23493 ... This protein and another 2 members, E2F1 and E2F2, have an additional cyclin binding domain. This protein binds specifically to ...
Cyclin dependant kinases (CDK) Cyclins DNA helicase DnaA Pre-replication complex Origin+Recognition+Complex at the US National ... Weinreich M, Liang C, Chen HH, Stillman B (September 2001). "Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the ... Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature. ... Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates ...
Cheng A, Ross KE, Kaldis P, Solomon MJ (November 1999). "Dephosphorylation of cyclin-dependent kinases by type 2C protein ... MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by ... This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. ... "Entrez Gene: PPM1A protein phosphatase 1A (formerly 2C), magnesium-dependent, alpha isoform". Flajolet M, Rakhilin S, Wang H, ...
This phosphatase has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle ... Cheng A, Ross KE, Kaldis P, Solomon MJ (2000). "Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases ... Cheng A, Kaldis P, Solomon MJ (2000). "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha ... "Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms". J. Biol. Chem. ...
... including cyclins and cyclin-dependent kinases. Unlike bacteria, eukaryotic DNA replicates in the confines of the nucleus. The ... Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature. ... The Mcm complex is recruited at late G1 phase and loaded by the ORC-Cdc6-Cdt1 complex onto the DNA via ATP-dependent protein ... Cdk-dependent phosphorylation of Mcm proteins promotes their export out of the nucleus along with Cdt1 during S phase, ...
Nguyen VQ, Co C, Li JJ (June 2001). "Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms". Nature. ... These control mechanisms rely on cyclin-dependent kinase (CDK) activity. DNA replication control mechanisms cooperate to ... When cyclin E is overexpressed in U-2-OS cell lines, the ATM/ATR-regulated DNA damage network results in increases in Ser 15- ... CDK-dependent phosphorylation of the MCM2-7 proteins results in the complex's export from the nucleus. (Cdt1 which associates ...
These include: Roscovitine is an inhibitor of cyclin-dependent kinase. It increases the current of calcium in neostriatal ... Cav2.1 voltage-dependent calcium channel Nimmrich V, Gross G (October 2012). "P/Q-type calcium channel modulators". Br. J. ... The P-type calcium channel is a type of voltage-dependent calcium channel. Similar to many other high-voltage-gated calcium ... The response is dose dependent as concentrations of 20nM and 200nM of Aβ globulomer are necessary for significant increase of ...
... by cyclin-dependent kinase 2-cyclin E and its role in centrosome duplication". The Journal of Biological Chemistry. 276 (24): ... "CDK2 cyclin dependent kinase 2 [Homo sapiens (human)]". Gene - NCBI. Retrieved 1 December 2019. Hinchcliffe EH, Li C, Thompson ... This link between the cell cycle and the centrosome cycle is mediated by cyclin-dependent kinase 2 (Cdk2). Cdk2 is a protein ... Matsumoto Y, Hayashi K, Nishida E (April 1999). "Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in ...
... cyclin-dependent kinase 12 is a protein kinase that in humans is encoded by the CDK12 gene. This enzyme is a member of ... "Entrez Gene: CDK12 cyclin-dependent kinase 12". Human CDK12 genome location and CDK12 gene details page in the UCSC Genome ... cyclin-dependent kinase protein family. GRCh38: Ensembl release 89: ENSG00000167258 - Ensembl, May 2017 GRCm38: Ensembl release ... Ko TK, Kelly E, Pines J (Oct 2001). "CrkRS: a novel conserved Cdc2-related protein kinase that colocalises with SC35 speckles ...
"Targets of the cyclin-dependent kinase Cdk1". Nature. 425 (6960): 859-864. Bibcode:2003Natur.425..859U. doi:10.1038/nature02062 ... Human protein kinases use ATP as a cofactor to phosphorylate substrate proteins. Kinases play critical roles in complex cell ... Hole-modified kinase and bumped ATP analog pairs enabled substrate profiling of several other kinases, including CDK1, Pho85, ... steric bulk precluded binding to the wild type v-Src kinase. In mammalian cell lines, active v-Src kinase is required for ...
"CDK8 cyclin-dependent kinase 8 [Homo sapiens]". "CTDP1 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) ... 2002). "A kinase-cyclin pair in the RNA polymerase II holoenzyme". Nature. 374 (6518): 193-6. doi:10.1038/374193a0. PMID ... TFIIH is a large protein complex that contains among others the CDK7/cyclin H kinase complex and a DNA helicase. TFIIH has ... Subsequent to the action of TFIIH kinase, Ser2 residues are phosphorylated by CTDK-I in yeast (CDK9 kinase in metazoans). Ctk1 ...
SKP2 targets p27Kip-1, an inhibitor of cyclin-dependent kinases (CDKs). CDKs2/4 partner with the cyclinsE/D, respectively, ... This is achieved by continuous control of cyclins/CDKs levels through ubiquitination and degradation. When cyclin E is ... The level of cyclins, as the name suggests, are high only at certain time point during cell cycle. ... Moreover, ubiquitination can also act to turn on/off the kinase activity of a protein. The critical role of phosphorylation is ...
2004). "Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation". J. Biol. Chem. 279 (17): 17283-8. doi: ... 2004). "Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding ... Examples of orthologs in other species include: S. pombe - CDT1 (CDC10-dependent transcript 1) Drosophila melanogaster - ' ...
Malumbres M, Ortega S, Barbacid M. «Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors.» Biol Chem ... Toll-like Receptor-4 (TLR4) Down-regulates MicroRNA-107, Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6.» J Biol ... Increasing Macrophage Adhesion via Cyclin-dependent Kinase 6." (2011) His scientific career has been awarded with prizes such ... "Genetic analysis of mammalian cyclin-dependent kinases and their inhibitors." (2000). "Toll-like Receptor-4 (TLR4) Down- ...
Drapkin R, Le Roy G, Cho H, Akoulitchev S, Reinberg D (1996). "Human cyclin-dependent kinase-activating kinase exists in three ... a cyclin-dependent kinase-activating kinase (CAK) assembly factor". Cancer Res. 55 (24): 6058-62. PMID 8521393. Vandel L, ... GTF2H1 has been shown to interact with: Cyclin-dependent kinase 7, E2F1, ERCC2, Estrogen receptor alpha, TCEA1, and XPB. ... García-Martínez LF, Mavankal G, Neveu JM, Lane WS, Ivanov D, Gaynor RB (1997). "Purification of a Tat-associated kinase reveals ...
De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M, Kim SH (1997). "Inhibition of cyclin-dependent kinases by purine ... Doree M, Galas S (1994). "The cyclin-dependent protein kinases and the control of cell division". FASEB J. 8 (14): 1114-1121. ... Seliciclib (roscovitine or CYC202) is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase ( ... Schang LM, Rosenberg A, Schaffer PA (2000). "Roscovitine, a specific inhibitor of cellular cyclin-dependent kinases, inhibits ...
SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ ... "NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription". Genes & Development. 14 (18): ... The mitotic kinase aurora B phosphorylates histone H3 at serine 10, triggering a cascade of changes that mediate mitotic ... NPAT activates histone gene expression only after it has been phosphorylated by the G1/S-Cdk cyclin E-Cdk2 in early S phase.[ ...
Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which ... Simone C, Giordano A (2007). "Abrogation of signal-dependent activation of the cdk9/cyclin T2a complex in human RD ... This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb ... "MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner". Mol. Cell. Biol. 23 (14): 4859-69 ...
The cell cycle is regulated by a series of signalling factors and complexes such as cyclin-dependent kinases and p53, to name a ...
... , NCK5AI, P39, p39nck5ai, cyclin-dependent kinase 5, regulatory subunit 2 (p39), cyclin dependent kinase 5 regulatory ... cyclin-dependent protein kinase 5 activator activity. • lipid binding. Cellular component. • cytoplasm. • cyclin-dependent ... 2002). "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent ... positive regulation of protein kinase activity. • regulation of cyclin-dependent protein serine/threonine kinase activity. • ...
Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. „Cell". 75 (4), s. 805-816, 1993. ... a b Entrez Gene: CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1). ... Suppression of cell transformation by the cyclin-dependent kinase inhibitor p57KIP2 requires binding to proliferating cell ...
Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by specific cyclins that ... is one of the 19S subcomponents that also tightly binds the cyclin-dependent kinase CDK4 and plays a key role in recognizing ... In particular, exit from mitosis requires the proteasome-dependent dissociation of the regulatory component cyclin B from the ... the ATP-dependent proteolytic complex that was responsible for ubiquitin-dependent protein degradation was discovered and was ...
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ...
cyclin binding. • cyclin-dependent protein kinase activating kinase activity. • cyclin-dependent protein serine/threonine ... CDKN1A, CAP20, CDKN1, CIP1, MDA-6, P21, SDI1, WAF1, p21CIP1, cyclin-dependent kinase inhibitor 1A, cyclin dependent kinase ... also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) ... 1994). "p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest ...
... preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase ...
All these phases in the cell cycle are highly regulated by cyclins, cyclin-dependent kinases, and other cell cycle proteins. ... Generation of pressure is dependent on formin-mediated F-actin nucleation[71] and Rho kinase (ROCK)-mediated myosin II ... This can occur when cells become overcrowded (density-dependent inhibition) or when they differentiate to carry out specific ... Ramanathan SP, Helenius J, Stewart MP, Cattin CJ, Hyman AA, Muller DJ (February 2015). "Cdk1-dependent mitotic enrichment of ...
... endothelin receptor A and cyclin dependent kinase inhibitor. Mutations in interleukin 6 may be protective.[citation needed]. ...
cyclin-dependent protein serine/threonine kinase inhibitor activity. • protein binding. • cyclin-dependent protein kinase ... cyclin-dependent protein kinase holoenzyme complex. • nucleus. • nucleoplasm. • cytosol. • intracellular membrane-bounded ... Cyclin-dependent kinase inhibitor 1A (p21, Cip1). Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human ... regulation of cyclin-dependent protein serine/threonine kinase activity. • G1/S transition of mitotic cell cycle. • G2/M ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase" ... "Recruitment of phosphatidylinositol 3-kinase to CD28 inhibits HIV transcription by a Tat-dependent mechanism". J. Immunol. 169 ... A dose-dependent response was not observed, raising questions about the robustness of the findings.[21] ... of cellular CDK9 and cyclin T1, and hence increases the production of full-length viral RNA.[8] ...
"CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression". Cell. 151 (6): 1308-18. doi: ... "The turn motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C". The Journal of Biological ...
Jiang MC, Liao CF, Tai CC (June 2002). "CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial ... "Association of p120, a tyrosine kinase substrate, with E-cadherin/catenin complexes". The Journal of Cell Biology. 128 (5): ... Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent ... The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein composed of five extracellular cadherin repeats, a ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... Buhl AM, Osawa S, Johnson GL (1995). "Mitogen-activated protein kinase activation requires two signal inputs from the human ... 2bcj: Crystal Structure of G Protein-Coupled Receptor Kinase 2 in Complex with Galpha-q and Gbetagamma Subunits ...
Finally, the Akt protein kinase promotes cell survival through two pathways. Akt phosphorylates and inhibits Bad (a Bcl-2 ... Caspases are proteins that are highly conserved, cysteine-dependent aspartate-specific proteases. There are two types of ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... the protein is cleaved by a calcium-dependent calpain protease ... "Apoptosis induced by Oropouche virus infection in HeLa cells is dependent on virus protein expression". Virus Research. 149 (1 ...
A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases. As their name implies ... "Biochemical characterization of the human cyclin-dependent protein kinase activating kinase. Identification of p35 as a novel ... CDKs are heavily dependent on specific cyclin molecules for activation. Once combined, the CDK-cyclin complex is capable of ... Herbst EA, MacPherson RE, LeBlanc PJ, Roy BD, Jeoung NH, Harris RA, Peters SJ (Jan 2014). "Pyruvate dehydrogenase kinase-4 ...
November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q ... Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression. Clonal rearrangements of the immunoglobulin ... July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601-6. PMID ...
GTP-dependent protein binding. • GTPase activity. • mitogen-activated protein kinase kinase kinase binding. • protein binding. ... Cyclin. *A (A1, A2). *B (B1, B2, B3). *D (D1, D2, D3) ... "The MAP kinase kinase kinase MLK2 co-localizes with activated ... protein kinase binding. • nucleotide binding. • GTP binding. • identical protein binding. Cellular component. • cytoplasm. • ... regulation of protein kinase activity. • regulation of attachment of spindle microtubules to kinetochore. • regulation of small ...
... and the cyclin dependent kinase inhibitors P27 and P21.». Leuk. Lymphoma 43 (1): 51-7. PMID 11908736. doi:10.1080/ ... de 2000). «Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of ... Transforming growth factor-beta is a potent immunosuppressive agent that inhibits IL-1-dependent lymphocyte proliferation». J ...
... cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143-57. doi:10.1038/sj.onc.1201252. PMID 9244350.. ... "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): ... "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ...
Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 2001). "Amphiphysin 1 binds the cyclin-dependent kinase ... Chen-Hwang MC, Chen HR, Elzinga M, Hwang YW (May 2002). "Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A ... Micheva KD, Ramjaun AR, Kay BK, McPherson PS (September 1997). "SH3 domain-dependent interactions of endophilin with ...
... phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase ...
Cyclin. *Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Gαs activates the cAMP-dependent pathway by stimulating the production of cyclic AMP (cAMP) from ATP. This is accomplished by ... The cAMP-dependent pathway is used as a signal transduction pathway for many hormones including:. *ADH - Promotes water ... cAMP can then act as a second messenger that goes on to interact with and activate protein kinase A (PKA). PKA can ...
These transitions are controlled by the cyclin-dependent kinase Cdk1.[6] Though the proteins that control Cdk1 are well ... a cyclin-dependent kinase, on a tyrosine residue. Cdc2 drives entry into mitosis by phosphorylating a wide range of targets. ... The protein kinase Cdr2 (which negatively regulates Wee1) and the Cdr2-related kinase Cdr1 (which directly phosphorylates and ... Wu L, Russell P (June 1993). "Nim1 kinase promotes mitosis by inactivating Wee1 tyrosine kinase". Nature. 363 (6431): 738-41. ...
The process follows fertilization, with the transfer being triggered by the activation of a cyclin-dependent kinase complex.[1] ... high levels of proteins that control cell cycle progression such as the cyclins and their associated cyclin-dependent kinases ( ... cdk). The complex Cyclin B/CDK1 a.k.a. MPF (maturation promoting factor) promotes entry into mitosis. ...
... die during embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase ... Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca2+/calmodulin-dependent kinase ( ... Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A ... The last is TAFII250 which has a Kinase domain at the N-terminus region, two bromodomains located at the C-terminus region and ...
CDK6; cyclin D1, cyclin D2, cyclin D3 CDK7; cyclin H CDK8; cyclin C CDK9; cyclin T1, cyclin T2a, cyclin T2b, cyclin K CDK10 ... cyclin A, cyclin B CDK2; cyclin A, cyclin E CDK3; cyclin C CDK4; cyclin D1, cyclin D2, cyclin D3 CDK5; CDK5R1, CDK5R2. See also ... A cyclin-dependent kinase inhibitor (CKI) is a protein that interacts with a cyclin-CDK complex to block kinase activity, ... Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell ...
CDK4, CMM3, PSK-J3, cyclin-dependent kinase 4, cyclin dependent kinase 4. ... protein kinase activity. • kinase activity. • protein serine/threonine kinase activity. • cyclin-dependent protein serine/ ... "Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proc. Natl. Acad. Sci. U.S. ... Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the CDK4 gene ...
"Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C". Proceedings of the National ... protein serine/threonine kinase activity. • cyclin-dependent protein serine/threonine kinase activity. ... The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. CDK8 and cyclin C associate ... "Entrez Gene: CDK8 cyclin-dependent kinase 8".. *^ Nemet J, Jelicic B, Rubelj I, Sopta M (Feb 2014). "The two faces of Cdk8, a ...
... like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate ... Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that ... De Bondt HL, Rosenblatt J, Jancarik J, Jones HD, Morgan DO, Kim SH (June 1993). "Crystal structure of cyclin-dependent kinase 2 ... Overview of all the structural information available in the PDB for UniProt: P06493 (Cyclin-dependent kinase 1) at the PDBe-KB. ...
Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell ... Cyclin Dependent Kinases in the Cell Cycle. Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene ... Control of Cyclin Dependent Kinases. Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, ...
Activation of cyclin A-dependent protein kinases during apoptosis. W Meikrantz, S Gisselbrecht, S W Tam, and R Schlegel ... activation of cyclin A-dependent protein kinases, is also an important event during apoptosis. ... to 7-fold increases in cyclin A-associated histone H1 kinase activity, levels approximating the mitotic value. Where examined, ... both Cdc2 and Cdk2, the catalytic subunits known to associate with cyclin A, were activated. Stable overexpression of bcl-2 ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
In plants, different families of cyclin-dependent kinases (CDKs) and cyclins have been identified, indicating that also in ... Regulation of cyclin-dependent kinases in Arabidopsis thaliana.. Stals H1, Casteels P, Van Montagu M, Inzé D. ... Cyclin-Dependent Kinases/antagonists & inhibitors. *Cyclin-Dependent Kinases/genetics*. *Cyclin-Dependent Kinases/metabolism ...
cyclin-dependent kinase B1;2 [Arabidopsis thaliana] cyclin-dependent kinase B1;2 [Arabidopsis thaliana]. gi,42569741,ref,NP_ ... Encodes a member of a plant specific family of cyclin dependent kinases. Also Known As: AT2G38620, CYCLIN-DEPEN... ... cyclin-dependent kinase B1;2 [Arabidopsis thaliana]. NCBI Reference Sequence: NP_181396.2 ... CDK-related protein kinases in plants. [Plant Mol Biol. 2000] CDK-related protein kinases in plants.. Joubès J, Chevalier C, ...
... the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell proliferation and its ... found to be dependent on these protein kinases, but the reg- ulatory assumption intrinsic to cyclin-dependent kinases, a stable ... CDK CKI Zellzyklus biochemistry biology cancer cell cell cycle cellular differentiation cellular growth cyclin-dependent kinase ... More than 10 years ago, the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
... the inhibitory kinase for cyclin-dependent kinase (CDK), is down-regulated primarily through proteasome-dependent degradation ... cyclin-dependent kinase; Wee1A, somatic Wee1; β-TrCP, β-transducin repeat-containing protein; Plk1, polo-like kinase 1; PBD, ... phosphorylation of serines S53 and S123 of Wee1A by polo-like kinase 1 (Plk1) and cyclin-dependent kinase (CDK), respectively, ... Cyclin-dependent kinase (CDK) phosphorylation destabilizes somatic Wee1 via multiple pathways. Nobumoto Watanabe, Harumi Arai, ...
Cyclin-dependent kinase synonyms, Cyclin-dependent kinase pronunciation, Cyclin-dependent kinase translation, English ... dictionary definition of Cyclin-dependent kinase. n. Any of various enzymes that catalyze the transfer of a phosphate group ... Cyclin-dependent kinase - definition of Cyclin-dependent kinase by The Free Dictionary https://www.thefreedictionary.com/Cyclin ... kinase. (redirected from Cyclin-dependent kinase). Also found in: Thesaurus, Medical, Acronyms, Encyclopedia, Wikipedia. ki· ...
We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), ...
Summary Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division ... Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase associated with P-TEFb. This kinase was found to be a component ... Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase ... Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase ...
Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. ... Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins ... CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle ... Associates primarily with cyclin-H (CCNH) and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to ...
The Gene Ontology (GO) project is a collaborative effort to address the need for consistent descriptions of gene products across databases. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated gene data at MGI are provided in Term Detail reports.
... By University of Edinburgh Sep 4, 2006, 16:41. ...
Cyclin dependent kinase 4Imported. ,p>Information which has been imported from another database using automatic procedures.,/p ... tr,Q9JKW8,Q9JKW8_MOUSE Cyclin dependent kinase 4 (Fragment) OS=Mus musculus GN=CDK4 PE=4 SV=1 ... IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. ... IPR011009. Kinase-like_dom_sf. IPR000719. Prot_kinase_dom. IPR017441. Protein_kinase_ATP_BS. ...
Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle ... Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ... IPR011009, Kinase-like_dom_sf. IPR000719, Prot_kinase_dom. IPR017441, Protein_kinase_ATP_BS. IPR008271, Ser/Thr_kinase_AS. ...
J:17392 Eipers PG, et al., Localization of the expressed human p58 protein kinase chromosomal gene to chromosome 1p36 and a ...
... Cell Cycle. ... Several groups including our own have demonstrated that induction of cyclin-dependent kinase (CDK) inhibitor p27Kip1 protein is ... Cyclin-Dependent Kinase Inhibitor p27 / metabolism* * Cyclin-Dependent Kinases / antagonists & inhibitors* * Cyclin-Dependent ... By inhibiting cyclin D and c-Myc, trastuzumab releases the sequestrated p27bKip1 protein from cyclin D-CDK4/6 complexes and ...
The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S ... The cyclin-dependent kinase Cdk2 associates with cyclins A, D, and E and has been implicated in the control of the G1 to S ... The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases Cell. 1993 Nov 19;75(4):805-16. doi: ... cyclin E-Cdk2, cyclin D1-Cdk4, and cyclin D2-Cdk4 complexes. Cotransfection experiments indicate that CIP1 and SV40 T antigen ...
Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. ... Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve ... cdk Proteins; Cyclin-Dependent Protein Kinases; Cyclin Dependent Kinases; Cyclin Dependent Protein Kinases ... Protein Kinases: 9706*Protein-Serine-Threonine Kinases: 1353*Cyclin-Dependent Kinases: 639*Cyclin-Dependent Kinase 4: 285 ...
"Both p16 and p21 families of cyclin-dependent kinase (CDK) inhibitors block the phosphorylation of cyclin-dependent kinases by ... "Entrez Gene: CDK7 cyclin-dependent kinase 7 (MO15 homolog, Xenopus laevis, cdk-activating kinase)".. ... "Human cyclin-dependent kinase-activating kinase exists in three distinct complexes". Proceedings of the National Academy of ... a cyclin-dependent kinase-activating kinase (CAK) assembly factor". Cancer Research. 55 (24): 6058-62. PMID 8521393.. ...
Cyclin-Dependent Kinase 2. Cyclin-Dependent Kinase 4. Cyclin-Dependent Kinase Inhibitor p16 / metabolism. Cyclin-Dependent ... EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 3.4. ... Cyclin-Dependent Kinase Inhibitor p27. Cyclin-Dependent Kinases / antagonists & inhibitors*, metabolism. Cyclins / metabolism. ... 0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase ...
Compare Anti-cyclin-dependent kinase 16 S homeolog Antibody Products from leading suppliers on Biocompare. View specifications ... Your search returned 2 cyclin-dependent kinase 16 S homeolog Antibodies across 2 suppliers. ...
Cyclin-dependent kinase inhibitors (CDKIs) play a critical role in negatively regulating the proliferation of cardiomyocytes, ... Cyclin-Dependent Kinase Inhibitor p27 / genetics, metabolism*. Gene Expression Regulation, Developmental. Heart / embryology*. ... The role of cyclin-dependent kinase 5 and a novel regulatory subunit in regulating muscle differentiation and patterningGenes ... Cyclin-dependent kinase inhibitor expression in human heart failure. A comparison with fetal developmentEur Heart J 1999;20:604 ...
... cyclin-dependent] kinase 4-alternative reading frame (INK4A-ARF) and cyclin-dependent kinase 4, are involved in the regulation ... A dominant-negative cyclin D1 mutant prevents nuclear import of cyclin-dependent kinase 4 (CDK4) and its phosphorylation by CDK ... Regulation of cyclin-dependent kinase 4 during adipogenesis involves switching of cyclin D subunits and concurrent binding of ... Concurrent overexpression of cyclin D1 and cyclin-dependent kinase 4 (Cdk4) in intestinal adenomas from multiple intestinal ...
Cyclin-Dependent Kinase-9. An RNAPII Kinase at the Nexus of Cardiac Growth and Death Cascades. Motoaki Sano, Michael D. ... Cyclin-Dependent Kinase-9: An RNAPII Kinase at the Nexus of Cardiac Growth and Death Cascades Ryozo Nagai Guest Editor ... Strikingly, RNA polymerase II (RNAPII) is itself a substrate for two protein kinases-the cyclin-dependent kinases Cdk7 and Cdk9 ... P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol Cell Biol. 2000; 20: 2629-2634. ...
  • solved the structure of human cyclin A-CDK2 complex to 2.3 Angstrom resolution. (wikipedia.org)
  • It is at this essential residue (T160 in CDK2 complexes, T177 in CDK6 complexes) that enzymatic ATP-phosphorylation of CDK-cyclin complexes by CAK (cyclin activating kinase, referring to the CDK7-Cyclin H complex in human cells) takes place. (wikipedia.org)
  • Cyclin A is also produced, which binds to CDK2 and stimulates DNA replication. (news-medical.net)
  • Where examined, both Cdc2 and Cdk2, the catalytic subunits known to associate with cyclin A, were activated. (pnas.org)
  • A dominant-negative Cdc2 mutant arrested cells at the G2 to M phase transition, whereas mutants of the cyclin-dependent kinases Cdk2 and Cdk3 caused a G1 block. (sciencemag.org)
  • By inhibiting cyclin D and c-Myc, trastuzumab releases the sequestrated p27bKip1 protein from cyclin D-CDK4/6 complexes and increase the effect of p27Kip1 on CDK2-cyclin E complexes. (nih.gov)
  • By stimulating minibrain related kinase (MIRK), trastuzumab stabilizes p27Kip1 in the nucleus, which increases inhibitory action of p27Kip1 on CDK2. (nih.gov)
  • Two such proteins, cyclin-dependent kinase-2 (Cdk2) and its downstream target, the retinoblastoma gene product (Rb), also play a critical role in the control of apoptosis. (nih.gov)
  • CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. (researchandmarkets.com)
  • This G1 arrest is associated with a dramatic decrease in the protein levels of Cdk2 and cyclin E correlated with an inhibition of the Cdk2 kinase activity. (biomedsearch.com)
  • CDK2 and CDK1 are two closely related kinases that play overlapping roles during cell division, contributing to the phosphorylation and inactivation of the retinoblastoma (Rb) tumor suppressor gene product throughout late G 1 , S, and G 2 -M phases ( 5 - 7 ). (aacrjournals.org)
  • Consistent with a key role for CDK6 as a D-cyclin partner in thymocytes, knockout (KO) of CDK4 or CDK2 was shown to have no significant effect on T-cell development ( 11 , 12 ), but significantly decreased thymic cellularity was observed in a CDK6 KO animal ( 13 ). (aacrjournals.org)
  • p16 Ink4 inhibited cdk4, but not cdk2, kinase activity, producing partial inhibition of VSMC growth in vitro. (ahajournals.org)
  • Progression through G 1 and entry into the S phase is regulated by the formation and activation of cyclin/cyclin-dependent kinase (CDK) complexes, predominantly cyclin D-cdk4/6 and cyclin E-cdk2. (ahajournals.org)
  • To address this apparent paradox, we examined possible predictors of the sensitivity of 10 breast cancer cell lines to erlotinib in light of cyclin-dependent kinase 2 (CDK2), considered the farthest downstream kinase that controls cell cycling in the EGFR signaling pathway. (aacrjournals.org)
  • Reports that cell lines showing sensitivity to EGFR-TKIs showed G 1 arrest after treatment with EGFR-TKIs ( 11 - 13 ) led us to study the potential relationship between cyclin-dependent kinases (CDK), particularly CDK2 ( 12 , 13 ) and erlotinib sensitivity. (aacrjournals.org)
  • CDK2 regulates the G 1 -S phase transition and, within the EGFR signaling pathway, is the farthest downstream molecule with known kinase activity ( 13 - 15 ). (aacrjournals.org)
  • Xylocydine (4-amino-6-bromo-7-(β- l -xylofuranosyl)pyrrolo[2,3-d]pyrimidine-5-carboxamide) blocks cyclin-dependent kinase CDK1 and CDK2/cyclin A activity in vitro (IC 50 1.4 and 61 nM, respectively) while minimally inhibiting the three other Ser/Thr protein kinases tested (IC 50 21-86 μM). (aspetjournals.org)
  • Activity of CDK2 is maximal during S phase and G2, 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. (biomol.com)
  • Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (biomol.com)
  • NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. (biomol.com)
  • 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. (biomol.com)
  • These cyclin-CDK complexes, as well as cyclin E-CDK2 complexes later in the cell cycle, phosphorylate retinoblastoma protein (Rb). (asm.org)
  • We identified that Thr85 immediately prior to the NLS of PTHrP was phosphorylated by CDC2-CDK2 and phosphorylation was cell cycle-dependent. (garvan.org.au)
  • For example, the G1/S transition is regulated by Cdk2/cyclin E, Cdk3/unknown cyclin, Cdk4/cyclin D1-3, Cdk6/cyclin D1, and Cdk8/cyclin C. The frequent deregulation of Cdks and their regulators in cancer has stimulated the search for potent and selective inhibitors of Cdks for both research and therapeutic use. (merckmillipore.com)
  • Cdk2 was also phophorylated by this mytl kinase less than was done by the weel kinase. (nii.ac.jp)
  • Publications] Ohkubo,Y.: 'SV40 large T antigen reinduces the cell cyc10 in terminally differentiated myotubes through inducing cdk2, cdc 2 and their partner cyclins' Exptl. (nii.ac.jp)
  • 5 For example, p27 Kip1 promotes the assembly of CDK4/cyclin D complexes, thus facilitating CDK2/cyclin E activation through the G 1 /S phase. (ahajournals.org)
  • The structure of CDKs in complex with a cyclin subunits (CDKC) has long been a goal of structural and cellular biologists starting in the 1990s when the structure of unbound cyclin A was solved by Brown et al. (wikipedia.org)
  • These cyclin binding sites are the regions of highest variability in CDKs despite relatively high sequence homology surrounding the αL-12 Helix motif of this structural component. (wikipedia.org)
  • These cyclins oscillate, increasing and decreasing at different stages, binding to CDKs and driving the cell cycle forward. (news-medical.net)
  • In addition to cyclin levels, this provides and additional way to control the activity of CDKs. (news-medical.net)
  • In plants, different families of cyclin-dependent kinases (CDKs) and cyclins have been identified, indicating that also in plants the progression through the cell cycle is regulated by CDKs. (nih.gov)
  • More than 10 years ago, the discovery of cyclin-dependent ki- nases (Cdks) ushered in a new era in the understanding of cell proliferation and its control. (springer.com)
  • For example, although Cdks appear to be highly conserved phylogenetically, cyclins are much less so. (springer.com)
  • However, due to the high degree of structural homology within the CDK protein family, putative small-molecule CDK inhibitors may exert their effects through combinatorial inhibition of multiple CDKs and other closely related serine/threonine kinases. (aacrjournals.org)
  • Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. (aspetjournals.org)
  • Therefore, there is an urgent need for new cancer-targeted drugs, which has led (inter alia) to the development of molecules that can specifically inhibit cyclin-dependent kinases (CDKs). (eurekaselect.com)
  • Clinical resistance to CDK inhibitors has not yet been described, but by comparing CDKs to other kinases, and CDK inhibitors to other clinically used protein kinase inhibitors, we also discuss possible mechanisms that could lead to resistance to CDK inhibitors. (eurekaselect.com)
  • In mammalian cells, cell cycle traversal is regulated by cyclins and cyclin-dependent kinases (CDKs) that are in turn controlled by CDK inhibitors (CKIs) ( 31 ). (asm.org)
  • Drugs targeting the cell cycle-regulatory cyclin-dependent kinase (CDK) 4 and 6 have been approved for the treatment of hormone receptor-positive breast cancer, and inhibitors targeting other cell-cycle CDKs are currently in clinical trials. (aacrjournals.org)
  • Cyclin-dependent kinases (CDKs) are required for initiation of DNA replication in all eukaryotes, and appear to act at multiple levels to control replication origin firing, depending on the cell type and stage of development. (inserm.fr)
  • Deregulation of cyclin-dependent kinases (CDKs) has been associated with many cancer types and has evoked an interest in chemical inhibitors with possible therapeutic benefit. (eurekaselect.com)
  • Requirement for the cyclin dependent kinase (CDK) inhibitor p21 downstream of p53 suggests a pivotal role for CDKs in controlling IE gene repression in S/G2 and treatment of S/G2 cells with the CDK inhibitor roscovitine alleviates IE repression independently of p53. (prolekare.cz)
  • Progression through the G1, S, G2 and M phases of the cell cycle is controlled by cyclin-dependent kinases (Cdks) and cyclins. (diva-portal.org)
  • The eight cyclin-dependent protein kinases (Cdks) that have been identified to date play an essential role in the regulation of the cell cycle. (merckmillipore.com)
  • Extracts from a diverse collection of cell types and organisms were screened for proteins binding purvalanol B. In addition to validating CDKs as intracellular targets, a variety of unexpected protein kinases were recovered from the 95 matrix. (lancs.ac.uk)
  • Cell cycle progression is controlled by several cyclin-dependent kinases (CDKs) that associate with regulatory cyclins. (ahajournals.org)
  • Interaction of CDKs/cyclins with CDK inhibitory proteins (CKIs) attenuates CDK activity and promotes growth arrest. (ahajournals.org)
  • 5 CKIs of the Cip/Kip family (p21 Cip1 , p27 Kip1 , and p57 Kip2 ) bind to and inhibit a wide spectrum of CDK/cyclin holoenzymes, whereas members of the Ink4 family (p16 Ink4a , p15 Ink4b , p18 Ink4c , and p19 Ink4d ) are specific for cyclin D-associated CDKs. (ahajournals.org)
  • In CDK-cyclin complexes, this activation region is composed of a conserved αL-12 Helix and contains a key phosphorylatable residue (usually Threonine for CDK-cyclin partners, but also includes Serine and Tyrosine) that mediates the enzymatic activity of the CDK. (wikipedia.org)
  • Cyclin-dependent kinases are a type of serine/threonine kinase which are activated by cyclins to drive the progress of the cell cycle. (news-medical.net)
  • Once bound to a cyclin they act to phosphorylate many target proteins on serine or threonine amino acid residues. (news-medical.net)
  • Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) - Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase associated with P-TEFb. (medindia.net)
  • Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) pipeline Target constitutes close to 26 molecules. (medindia.net)
  • It also reviews key players involved in Cyclin Dependent Kinase 9 (Tat Associated Kinase Complex Catalytic Subunit or C 2K or Cell Division Cycle 2 Like Protein Kinase 4 or Cell Division Protein Kinase 9 or Serine/Threonine Protein Kinase PITALR or CDK9 or EC 2.7.11.22 or EC 2.7.11.23) targeted therapeutics development with respective active and dormant or discontinued projects. (medindia.net)
  • Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC 2.7.11.22 or EC 2.7.11.23) - Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene. (researchandmarkets.com)
  • Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC 2.7.11.22 or EC 2.7.11.23) pipeline Target constitutes close to 11 molecules. (researchandmarkets.com)
  • A gene on chromosome 5q31 that encodes a CMGC-type serine/threonine protein kinase of unknown function, which is thought to have a cyclin-binding region. (thefreedictionary.com)
  • Cyclin-dependent kinase-like 2 (Cdkl2) is a cdc2-related serine/threonine protein kinase that is postnatally expressed in various brain regions, including the cerebral cortex, entorhinal cortex, hippocampus, amygdala, and dorsal thalamus. (frontiersin.org)
  • Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase structurally homologous to the Cdk family members which modulate the cell cycle. (frontiersin.org)
  • This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. (creativebiomart.net)
  • It also reviews key players involved in Cyclin Dependent Kinase 7 (39 kDa Protein Kinase or CDK Activating Kinase 1 or Cell Division Protein Kinase 7 or TFIIH Basal Transcription Factor Complex Kinase Subunit or Serine/Threonine Protein Kinase 1 or CDK7 or EC 2.7.11.22 or EC 2.7.11.23) targeted therapeutics development with respective active and dormant or discontinued projects. (marketresearch.com)
  • Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
  • Each interacts with a different cyclin at a different phase, stimulating various target proteins and ensuring that vital stages of each phase are carried out before a cell moves onto the next phase. (news-medical.net)
  • Cdk9 interacts adversely with Gq-dependent pathways for hypertrophy, impairing the expression of numerous genes for mitochondrial proteins, and, in particular, suppressing master regulators of mitochondrial biogenesis and function, perioxisome proliferator-activated receptor-γ coactivator-1 (PGC-1), and nuclear respiratory factor-1 (NRF-1). (ahajournals.org)
  • The activity of CDK6 is very tightly controlled by association with D-cyclins ( 7 ) and two families of CDK inhibitors, including the CIP/KIP family and the inhibitors of CDK4 (INK4) family proteins ( 9 ). (aacrjournals.org)
  • Here we demonstrate that the budding yeast cyclin-dependent kinase Cdc28 directly regulates the formation of the DNA double-strand breaks that initiate recombination by phosphorylating the Mer2/Rec107 protein and thereby modulating interactions of Mer2 with other proteins required for break formation. (pubmedcentralcanada.ca)
  • This DNA damage is dependent on CDK1 and -2 as well as the replication proteins MCM2 and CDT1 but not CDC25A. (rupress.org)
  • The initial response to replicative stress is activated mainly by the ATR (ataxia telangiectasia and Rad3-related protein) kinase, which targets proteins such as p53, H2AX, and the CHK1 kinase. (rupress.org)
  • Cyclin-CDK complex gets activated after phosphorylation which results in release of proteins, that leads to cell proliferation. (psmarketresearch.com)
  • CDK inhibitors are the proteins that networks with a cyclin-CDK complex to inhibit the kinase activity of the complex, usually during G1 phase. (psmarketresearch.com)
  • The PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), which shares extensive sequence homology (approximately 70%) with cdk4, was identified as the earliest inducible member of the cdk family of proteins in human T lymphocytes induced to proliferate in vitro by stimulation either with phorbol 12,13-dibutyrate and ionomycin (PDB/I) or PHA. (jimmunol.org)
  • These proteins form active Cdk:cyclin complexes that phosphorylate specific substrates. (diva-portal.org)
  • To identify proteins which bind to mouse weel kinase, the yeast ' two-hybrid'system was used with a mouse cDNA library. (nii.ac.jp)
  • 3 Mitogenic stimuli activate CDK/cyclin holoenzymes, thus causing hyperphosphorylation of the retinoblastoma protein (pRb) and related "pocket" proteins from mid G 1 to mitosis. (ahajournals.org)
  • Moreover, the proto-oncogene c- myc plays a key role in p27 sequestration through modulation of the level of cyclin D and E proteins. (ahajournals.org)
  • The 1970s included the discovery of calmodulin-dependent protein kinases and the finding that proteins can be phosphorylated on more than one amino acid residue. (wikipedia.org)
  • 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)
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb ). (wikipedia.org)
  • Cell division protein kinase 8 is an enzyme that in humans is encoded by the CDK8 gene . (wikipedia.org)
  • The protein encoded by this gene is a member of the cyclin-dependent protein kinase (CDK) family. (wikipedia.org)
  • The differences at each stage are due to a balance between the gene expression of each cyclin and the ubiquitin-proteasome system which breaks them down. (news-medical.net)
  • Initially, a mitogenic stimulus leads to the upregulation of cyclin D gene expression, which binds to CDK4. (news-medical.net)
  • p27(KIP1) is a member of the CIP1/KIP1 family of cyclin-dependent kinase inhibitors and is a potential tumor suppressor gene. (thefreedictionary.com)
  • We have previously demonstrated that loss of one candidate gene at this locus, cyclin-dependent kinase inhibitor 2B (Cdkn2b), in mice promotes vascular SMC apoptosis and aneurysm progression. (jci.org)
  • Cell division protein kinase 7 is an enzyme that in humans is encoded by the CDK7 gene . (wikidoc.org)
  • M. Ubeda, D. M. Kemp, and J. F. Habener, "Glucose-induced expression of the cyclin-dependent protein kinase 5 activator p35 involved in Alzheimer's disease regulates insulin gene transcription in pancreatic β -cells," Endocrinology , vol. 145, no. 6, pp. 3023-3031, 2004. (hindawi.com)
  • CDKN2A (cyclin dependent kinase 2a / p16) Hybridization with Vysis CDKN2A/CEP 9 FISH Probe (Abbott Molecular, US) showing the CDKN2A gene on 9p21.3 (red signals) - Courtesy Adriana Zamecnikova. (atlasgeneticsoncology.org)
  • The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 ( cdk5 ) is abnormal in its structure. (jneurosci.org)
  • At the EGR1 gene locus, RV-cyclin increases and maintains RNA polymerase II (Pol II) occupancy after serum stimulation, in conjunction with increased and extended EGR1 gene expression. (sigmaaldrich.com)
  • The RV-cyclin increases CDK8 occupancy at the EGR1 gene locus before and after serum stimulation. (sigmaaldrich.com)
  • A gene on chromosome 9q34.1 that encodes a cyclin-dependent kinase, which regulates cell cycle progression. (thefreedictionary.com)
  • The gene codes for a protein, p15, which is an inhibitor of cyclin dependent kinases, and thus, acts as a negative regulator of cell proliferation. (cags.org.ae)
  • Mutations in the gene cause the protein to lose their capacity to block the Cyclin D/CDK activation, resulting in uncontrolled cell proliferations, and development of malignancies. (cags.org.ae)
  • This gene encodes a member of the p34Cdc2 protein kinase family. (antibodies-online.com)
  • The protein kinase encoded by this gene could be cleaved by caspases and was demonstrated to play roles in cell apoptosis. (antibodies-online.com)
  • 2 Cyclin-dependent kinase inhibitors (CKIs) are naturally occurring gene products that inhibit the cyclin-CDK activity leading to G 1 arrest. (ahajournals.org)
  • Transcriptome analysis of BCR-engaged B cells from Bach2 −/− mice revealed reduced expression of the antiapoptotic gene Bcl2l1 encoding Bcl-x L and elevated expression of cyclin-dependent kinase inhibitor (CKI) family genes, including Cdkn1a , Cdkn2a , and Cdkn2b . (jimmunol.org)
  • Activity of the kinase, determined by in vitro phosphorylation of recombinant truncated retinoblastoma tumor suppressor gene (Rb) protein (p60Rb), paralleled p40cdk6 protein amounts. (jimmunol.org)
  • Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. (frontiersin.org)
  • Here, we show that the block to IE gene expression during S and G2 phase can be overcome by both genotoxic stress and chemical inhibitors of cellular DNA replication, pointing to the involvement of checkpoint-dependent signaling pathways in controlling IE gene repression. (prolekare.cz)
  • Thus, a timely block to CDK activity not only secures phase specificity of the cell cycle dependent HCMV IE gene expression program, but in addition plays a hitherto unrecognized role in preventing the establishment of a latent-like state. (prolekare.cz)
  • This raised the possibility that HIV-1 gene expression in renal epithelium may also be critically dependent on CDK that control RNA polymerase II activity on the HIV-1 promoter ( 10 ). (asnjournals.org)
  • To investigate this process, we reduced endoreduplication in transgenic maize endosperm by ectopically expressing a gene encoding a dominant negative mutant form of cyclin-dependent kinase A. This gene was regulated by the 27-kD γ-zein promoter, which restricted synthesis of the defective enzyme to the endoreduplication rather than the mitotic phase of endosperm development. (plantcell.org)
  • A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic subunit of a protein kinase, cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin. (wikipedia.org)
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
  • Not only were both of the known cell cycle transitions, from G 1 to S phase and G2 to M phase, found to be dependent on these protein kinases, but the reg- ulatory assumption intrinsic to cyclin-dependent kinases, a stable inactive catalytic subunit (the Cdk) and an unstable requisite positive regulatory activating subunit (the cyclin), led to a simple model for cell cycle control. (springer.com)
  • This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. (medindia.net)
  • This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with CDK9 and cyclin T, which suggested a possible involvement of this protein in AIDS. (medindia.net)
  • Identification of the 23 kDa subunit of tau protein kinase II as a putative activator of CDK5 in bovine brain," FEBS Letters , vol. 342, no. 2, pp. 203-208, 1994. (hindawi.com)
  • CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. (researchandmarkets.com)
  • The dimeric enzyme consists of a catalytic subunit, CDK and a regulatory subunit, cyclin. (psmarketresearch.com)
  • Human Cdk subunit 1 ( Cks1 ), as well as S-phase kinase-associated protein 2 ( Skp2 ), is an essential and specific factor in the p27 proteolysis by SCF Skp2 ubiquitin ligase. (aacrjournals.org)
  • The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. (creativebiomart.net)
  • Both kinases are important negative regulators of CDK1 and -2. (rupress.org)
  • Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression, 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. (biomol.com)
  • Furthermore, MCF-7 cells treated with IV-2 showed increased Cdk1 kinase activity and a decrease in Cdk1 tyrosine phosphorylation, indicating that IV-2 did not directly inhibit Cdk1 or Cdc25 activities. (aspetjournals.org)
  • Cyclin-afhængig kinase 1 (Cdk1) er aktiveret i G2 fase af cellecyklus og regulerer mange cellulære veje. (jove.com)
  • Her præsenterer vi en protokol for en in vitro- kinase assay med Cdk1, som giver mulighed for identifikation af Cdk1-specifikke fosforylering websteder til oprettelse af cellulære mål for denne vigtige kinase. (jove.com)
  • Her, beskriver vi en in vitro- kinase assay, der bruges til at identificere Cdk1-specifikke fosforylering websteder. (jove.com)
  • I denne analyse, et oprenset protein er fosforyleres i vitro af kommercielt tilgængelige menneskelige Cdk1/cyclin B. vellykket fosforylering er bekræftet af SDS-PAGE og fosforylering websteder er efterfølgende identificeret ved massespektrometri. (jove.com)
  • Sammen præsentere disse protokoller en meget kraftfuld tilgang, der giver Cdk1-specifikke fosforylering websteder og muliggør Mekanistiske undersøgelser i hvordan Cdk1 kontrol af cellecyklus. (jove.com)
  • Cdk1, som er også kendt som celledeling cyklus protein 2 homolog (cdc2) er en master controller til cellecyklus i alle eukaryoter 1 , 2 , 3 , 4 , 5 , og phosphorylates en anslåede 8-13% af proteomet 6 , 7 . (jove.com)
  • I denne analyse, er kommercielt tilgængelige menneskelige Cdk1/cyclin B bruges til at phosphorylate en renset target protein in vitro . (jove.com)
  • Previously, we found that eIF4A interacts with cyclin-dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. (plantphysiol.org)
  • Olomoucine, a 2,6,9-trisubstituted purine, has been optimized for activity against CDK1/cyclin B by combinatorial and medicinal chemistry efforts to yield the purvalanol inhibitors. (lancs.ac.uk)
  • Cyclin-dependent kinase 6 (CDK6) bound to the inhibitor ribociclib (detail view). (news-medical.net)
  • Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. (aacrjournals.org)
  • Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. (aacrjournals.org)
  • These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies. (aacrjournals.org)
  • Cyclin-dependent kinase 6 (CDK6), a cyclin D-responsive regulator of the retinoblastoma protein (pRB) pathway, seems to be of central importance in T-cell development. (aacrjournals.org)
  • In contrast, cyclin D2 expression is high in the DN1-DN3 stages before pre-TCR assembly and barely detectable after pre-TCR assembly ( 10 ), suggesting that CDK6 may use different cyclin partners in the thymocyte developmental stages. (aacrjournals.org)
  • p15 interacts strongly with cyclin-dependent kinases CDK4 and CDK6, and inhibits their ability to interact with cyclins D, thereby blocking the CyclinD/CDK complex from phosphorylating the retinobloastoma protein (RB1). (cags.org.ae)
  • Regulation of synthesis and activity of the PLSTIRE protein (cyclin-dependent kinase 6 (cdk6)), a major cyclin D-associated cdk4 homologue in normal human T lymphocytes. (jimmunol.org)
  • Furthermore, increased accumulation of p40cdk6 protein and activity occurred in cells rendered "competent" (responsive to IL-2) by a brief treatment with PDB/I. Thus, increased accumulation of the protein and its activity begin before IL-2/IL-2 receptor interaction, suggesting that the cdk6-cyclin D2 complex might be involved in acquisition of the competent state in human T lymphocytes. (jimmunol.org)
  • Antigen receptor signaling or exposure to growth factors triggers de novo synthesis of D-type cyclins, which then associate with their catalytic partners CDK4 or CDK6. (asm.org)
  • p16 Ink4a , p15 Ink4b , p18 Ink4c and p19 Ink4d , and they bind specifically to Cdk4 and Cdk6, thereby negatively regulating their kinase activities and cell cycle progression. (diva-portal.org)
  • RV-cyclin does not increase activating phosphorylation events in the mitogen-activated protein kinase pathway and does not inhibit decay of IEG mRNAs. (sigmaaldrich.com)
  • Involvement of p38 mitogen-activated protein kinase in basic fibroblast growth factor-induced interl. (biomedsearch.com)
  • Resistance to BRAFV600E inhibitors is associated with reactivation of mitogen-activated protein kinase (MAPK) signaling at different levels in melanoma. (harvard.edu)
  • Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis, 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. (biomol.com)
  • CYCLIN-DEPENDENT KINASE G2 regulates salinity stress response and salt mediated flowering in. (deepdyve.com)
  • Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. (uniprot.org)
  • P16-INK4a interacts strongly with cyclin-dependent kinase 4 and cyclin-dependent kinase 6 and inhibits their ability to interact with cyclins D. P16-INK4a induces cell cycle arrest at G1 and G2/M checkpoints, blocking them from phosphorylating RB1 and preventing exit from G1 phase of the cell cycle. (atlasgeneticsoncology.org)
  • Graf L, Webel R, Wagner S, Hamilton ST, Rawlinson WD, Sticht H, Marschall M. The Cyclin-Dependent Kinase Ortholog pUL97 of Human Cytomegalovirus Interacts with Cyclins. (mdpi.com)
  • HIV-1 Tat protein interacts with CDK9 and cyclin T, suggesting CDK9 may have a role in AIDS. (thefreedictionary.com)
  • Retinoblastoma protein (Rb) usually functions to inhibit the transcription factor E2F, however, when cyclin-D-CDK4 phosphorylates the Rb protein, this relinquishes inhibition of E2F and leads to the production of genes required for entering the S phase. (news-medical.net)
  • The Cdk:cyclin complexes of the G1/S transition regulate the progression of cells into the S phase by phosphorylating the retinoblastoma protein (Rb). (diva-portal.org)
  • Moreover, a constitutively active mutant of the retinoblastoma protein (pRb) insensitive to CDK-dependent hyperphosphorylation inhibited both cell proliferation and migration. (ahajournals.org)
  • These effects were associated with increased binding of p21(WAF1/Cip1) and p27(Kip1) to cyclin D1- and E1-containing complexes and decreased retinoblastoma protein phosphorylation. (garvan.org.au)
  • Open form structures correspond most often to those complexes involved in transcriptional regulation (CDK 8, 9, 12, and 13), while closed form CDK-cyclin complex are most often involved in cell cycle progression and regulation (CDK 1, 2, 6). (wikipedia.org)
  • Dominant-negative mutations were used to address the requirement for kinases of this family in progression through the human cell cycle. (sciencemag.org)
  • Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (curehunter.com)
  • Associated with cyclin-D, CDK4 phosphorylates and inactivates retinoblastoma (Rb) protein family members and mediates progression through the G1- to the S-phase of the cell cycle. (springer.com)
  • Targeted degradation of the cyclin-dependent kinase inhibitor ICK4/KRP6 by RING-type E3 ligases is essential for mitotic cell cycle progression during Arabidopsis gametogenesis. (nextbio.com)
  • Strikingly, RNA polymerase II (RNAPII) is itself a substrate for two protein kinases-the cyclin-dependent kinases Cdk7 and Cdk9-that are activated by hypertrophic cues. (ahajournals.org)
  • The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. (mdpi.com)
  • Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay strongly suggested phosphorylation of pUL97 by the CDK9/cyclin T1 complex in a substrate concentration-dependent manner. (mdpi.com)
  • Study TPI-ALV-201 is examining the efficiency of alvocidib, an investigational inhibitor of cyclin-dependent kinase 9 (CDK9), in combination with the authorized agents cytarabine and mitoxantrone in relapsed/refractory AML patients whose leukemia depends on MCL-1. (thefreedictionary.com)
  • Biopharmaceutical company Probiodrug AG revealed on Friday the transfer of its experimental cyclin-dependent kinase 9 (CDK9) inhibitor programme to AstraZeneca (LSE:AZN)(NYSE:AZN) for an undisclosed amount. (thefreedictionary.com)
  • Vladimir Krystof, Sonja Baumli and Robert Furst, "Perspective of Cyclin-dependent kinase 9 (CDK9) as a Drug Target", Current Pharmaceutical Design (2012) 18: 2883. (eurekaselect.com)
  • [5] 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)
  • Protein function: Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and. (biomol.com)
  • Protein function: 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 G(1)/S transition. (biomol.com)
  • We isolated mouse mytl kinase which phosphorylate both T-14 and Y-15 in vitro. (nii.ac.jp)
  • These genes include cyclin E, which binds to CDK4, driving the cell cycle into the S phase. (news-medical.net)
  • It is normally activated by cyclin C and is required for transcription elongation of the serum response genes (immediate early genes [IEGs]) FOS, EGR1, and cJUN. (sigmaaldrich.com)
  • RV-cyclin does not control CDK8 specificity but instead enhances CDK8's effects on regulated genes, an important distinction for its use to delineate natural CDK8 targets. (sigmaaldrich.com)
  • We found that leaf cells facing the cut undergo CDK activation along with induction of a D-type cyclin, tip growth, and transcriptional activation of protonema-specific genes. (deepdyve.com)
  • CDK-dependent pRb hyperphosphorylation releases E2F transcription factors, thus contributing to the expression of several growth and cell cycle-regulatory genes with functional E2F-binding sites in their promoters. (ahajournals.org)
  • OSI Pharmaceuticals, Inc., and Genentech, Inc.) is an orally available quinazolinamine that competes with ATP for binding with the intracellular catalytic domain of EGFR tyrosine kinase (EGFR-TK) to inhibit the phosphorylation of EGFR-TK. (aacrjournals.org)
  • Protein kinases can be classed as catalytically active (canonical) or as pseudokinases, reflecting the evolutionary loss of one or more of the catalytic amino acids that position or hydrolyse ATP. (wikipedia.org)
  • Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
  • The weel kinase phosphorylates only Y-15 residue of cdc2 kinase and T-14 phosphorylation is observed in a intact cell. (nii.ac.jp)
  • The other kinase which phosphorylates T-14 of cdc2 kinase must exist. (nii.ac.jp)
  • Years later, the first example of a kinase cascade was identified, whereby Protein Kinase A (PKA) phosphorylates Phosphorylase Kinase. (wikipedia.org)
  • The difference between the forms lies within the binding of cyclin partners where closed form complexes have CDK-cyclin binding at both the C and N-termini of the activation loop of the CDK, whereas the open form partners bind only at the N-terminus. (wikipedia.org)
  • It is important to note that in CDK 1, 2 and 6, the T-loop and a separate C-terminal region are the major sites of cyclin binding in the CDK, and which cyclins are bound to each of these CDK is mediated by the particular sequence of the activation site T-loop. (wikipedia.org)
  • Study of this residue has shown that phosphorylation promotes a conformational change that prevents ATP and substrate binding by steric interference with these necessary binding sites in the activation loop of the CDK-cyclin complexes. (wikipedia.org)
  • This activity is aided by the notable flexibility that the Gly-rich loop has within the structure of most CDK allowing for its rotation toward the activation loop to have a significant effect on reducing substrate affinity without major changes in the overall CDK-cyclin complex structure. (wikipedia.org)
  • These findings suggest that at least one of the biochemical steps required for mitosis, activation of cyclin A-dependent protein kinases, is also an important event during apoptosis. (pnas.org)
  • Modulation of cyclin accumulation, and thereby Cdk activation, was proposed to be the overarching principle governing the passage through cell cycle phases. (springer.com)
  • Oxidative stress induces nucleo-cytoplasmic translocation of pancreatic transcription factor PDX-1 through activation of c-Jun NH 2 -terminal kinase," Diabetes , vol. 52, no. 12, pp. 2896-2904, 2003. (hindawi.com)
  • Previous work showed that the retroviral cyclin (RV-cyclin), encoded by WDSV, has separable cyclin box and transcription activation domains. (sigmaaldrich.com)
  • Both of RV-cyclin's functional domains, i.e., the cyclin box and the activation domain, are necessary for the overall enhancement of IEG expression. (sigmaaldrich.com)
  • Activation of two kinases, Dbf4-Cdc7 and cyclin-dependent kinases (CDK), coupled with B-type cyclins are necessary to form replisomes at two nascent replication forks and to initiate DNA replication ( B ell and D utta 2002 ). (genetics.org)
  • This action blocks downstream signal transduction and inhibits the tumorigenic effects associated with ligand-dependent and ligand-independent EGFR activation ( 1 , 2 ). (aacrjournals.org)
  • Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. (biomol.com)
  • Checkpoint-dependent rescue of IE expression strictly requires p53 and in the absence of checkpoint activation is mimicked by proteasomal inhibition in a p53 dependent manner. (prolekare.cz)
  • Activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. (reportsnreports.com)
  • Andreas Villunger and colleagues discuss the biology of the PIDDosome multiprotein complex and recent advances that link PIDDosome-dependent CASP2 activation to p53 activation in response to extra centrosomes. (biologists.org)
  • 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 p16 INK4a . (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)
  • Upon external signals, CDK inhibitors can be used to block the CDK kinase activity, thereby preventing the cell cycle from being driven forward. (news-medical.net)
  • For all of the apoptosis-inducing agents tested, the appearance of condensed chromatin was accompanied by 2- to 7-fold increases in cyclin A-associated histone H1 kinase activity, levels approximating the mitotic value. (pnas.org)
  • At the onset of M phase, the activity of somatic Wee1 (Wee1A), the inhibitory kinase for cyclin-dependent kinase (CDK), is down-regulated primarily through proteasome-dependent degradation after ubiquitination by the E3 ubiquitin ligase SCF β-TrCP . (pnas.org)
  • Furthermore, using deleted and mutant forms of Xic1, we show that neither its abilities to inhibit the cell cycle nor the great majority of CDK kinase activity are essential for Xic1's function in cardiomyocyte differentiation, an activity that resides in the N-terminus of the molecule. (biomedsearch.com)
  • CONCLUSION: Altogether, our results demonstrate that the CDKI Xic1 is required in Xenopus cardiac differentiation, and that this function is localized at its N-terminus, but it is distinct from its ability to arrest the cell cycle and inhibit overall CDK kinase activity. (biomedsearch.com)
  • It binds to cyclin-dependent kinase 8 (CDK8) and enhances its kinase activity. (sigmaaldrich.com)
  • How Cdk5-dependent phosphorylation reduces MEF2 transactivation activity remained unknown. (jneurosci.org)
  • DNA replication initiation in S. cerevisiae is promoted by B-type cyclin-dependent kinase (Cdk) activity. (genetics.org)
  • We found evidence that the S-phase cyclin Clb6 could promote initiation of replication without blocking reinitiation, and this activity was highly toxic when the ability of other cyclins to block reinitiation was prevented by mutation. (genetics.org)
  • We conclude that the mitotic kinase WEE1 and CHK1 jointly maintain balanced cellular control of Cdk activity during normal DNA replication, which is crucial to prevent the generation of harmful DNA lesions during replication. (rupress.org)
  • The results show that the mitotic kinase WEE1 is crucial for genome integrity during S phase in a manner dependent on Cdk activity. (rupress.org)
  • This evidence suggests that the Cdkl kinase family might be involved in behavioral modification, activity-dependent synaptic plasticity, and learning. (frontiersin.org)
  • Shortly after its purification, P-TEFb was found to have protein kinase activity ( 50 ). (asm.org)
  • CKIs act as brakes for the cell cycle, restraining the activity of cyclin-CDK complexes to maintain cells in the quiescent G 0 /G 1 phase or to induce cell cycle exit in proliferating cells. (asm.org)
  • In vitro, wild-type recombinant eIF4A1 and its phospho-null variant both support translation in cell-free wheat germ extracts dependent upon eIF4A, but the phosphomimetic variant does not support translation and also was deficient in ATP hydrolysis and helicase activity. (plantphysiol.org)
  • Flavopiridol and roscovitine, newly identified inhibitors of cyclin-dependent kinase-9, markedly decrease HIV-1 promoter activity in cell lines of various lineages. (asnjournals.org)
  • Recently, flavopiridol and roscovitine, small molecules that inactivate specific cell-cycle cyclin-dependent kinases (CDK), were found to inhibit CDK-9, markedly decreasing HIV-1 promoter activity in cell lines of various lineages ( 8 , 9 ). (asnjournals.org)
  • The Cyclin-Dependent Protein Kinase Inhibitor Set controls the biological activity of Cyclin-Dependent Protein Kinase. (merckmillipore.com)
  • Dinaciclib is a novel cyclin-dependent kinase inhibitor with significant clinical activity in relapsed and refractory chronic lymphocytic leukemia. (osu.edu)
  • 14-3-3 zeta protein did not affect the activity of weel kinase. (nii.ac.jp)
  • Overexpression of a wild-type cyclin-dependent kinase A increased enzyme activity but had no effect on endoreduplication. (plantcell.org)
  • By contrast, ectopic expression of the defective enzyme lowered kinase activity and reduced by half the mean C-value and total DNA content of endosperm nuclei. (plantcell.org)
  • Regulation of cyclin-dependent kinases in Arabidopsis thaliana. (nih.gov)
  • Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 , a protein important to the regulation of Myc. (thefreedictionary.com)
  • The convergence of Cdk5 phosphorylation-dependent caspase-mediated degradation of nuclear survival factors exemplified by MEF2 may represent a general process applicable to the regulation of other survival factors under diverse neurotoxic conditions. (jneurosci.org)
  • Using a dominant negative approach, in vitro cell proliferation assays, western blots, and flow cytometry showed that MAPK signaling via BRAFV600E promotes melanoma cell proliferation at G1 through AP-1-mediated negative regulation of the INK4 family member, cyclin-dependent kinase inhibitor 2C (CDKN2C), and the CIP/KIP family member, cyclin-dependent kinase inhibitor 1A (CDKN1A). (harvard.edu)
  • The CKIs p27 Kip1 and p21 Cip1 inactivate the cyclin-CDK complexes in the G 1 phase leading to cell cycle arrest, and thus function in growth regulation and wound repair. (ahajournals.org)
  • CDK with cyclin combines to form a cyclin-CDK complex for the regulation of cell cycle. (psmarketresearch.com)
  • The heterogeneity of kinases involved in phospho-regulation provides a fundamental basis for the sequential biochemical reactions that underlie the mechanisms of synaptic plasticity. (frontiersin.org)
  • The function of 14-3-3 zeta protein remained to be elucidated in relationto the regulation of G2 to M phase transition through weel kinase. (nii.ac.jp)
  • Therefore, kinases are critical in metabolism, cell signalling, protein regulation, cellular transport, secretory processes and many other cellular pathways, which makes them very important to human physiology. (wikipedia.org)
  • Several groups including our own have demonstrated that induction of cyclin-dependent kinase (CDK) inhibitor p27Kip1 protein is one of the key mechanisms of action of HER2-targeting antibodies. (nih.gov)
  • By inhibiting AKT and human kinase interacting stathmin (hKIS), trastuzumab blocks Thr157-, Thr198- and Ser10-induced p27Kip1 translocation from the nucleus to the cytosol, which increases the inhibitory effect of p27Kip1. (nih.gov)
  • This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). (creativebiomart.net)
  • The latest report Cyclin Dependent Kinase 4 - Pipeline Review, H2 2017, outlays comprehensive information on the Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (reportsnreports.com)
  • Furthermore, this report also reviews key players involved in Cyclin Dependent Kinase 4 (Cell Division Protein Kinase 4 or PSK J3 or CDK4 or EC 2.7.11.22) targeted therapeutics development with respective active and dormant or discontinued projects. (reportsnreports.com)
  • It has been shown that Notch-promoted survival and trophic effects in pre-T cells are mediated by the phosphatidylinositol 3-kinase (PI3K)-Akt pathway ( 6 ). (aacrjournals.org)
  • During this time, the MAPK/ERK pathway, the JAK kinases (a family of protein tyrosine kinases), and the PIP3-dependent kinase cascade were discovered. (wikipedia.org)
  • An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator," Journal of Biological Chemistry , vol. 270, no. 45, pp. 26897-26903, 1995. (hindawi.com)
  • Cyclin-dependent kinase 5 (Cdk5) mediates neurotoxic effects by phosphorylating and inhibiting MEF2. (jneurosci.org)
  • In contrast to MEF2A and MEF2D, MEF2C is not phosphorylated by Cdk5 after glutamate exposure and, therefore, resistant to neurotoxin-induced caspase-dependent degradation. (jneurosci.org)
  • These findings demonstrate Cdk5 phosphorylation-dependent destabilization of specific MEF2 isoforms as an important regulatory mechanism in mediating neurotoxin-induced death. (jneurosci.org)
  • p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. (frontiersin.org)
  • The key cell-cycle regulator Cdc2 belongs to a family of cyclin-dependent kinases in higher eukaryotes. (sciencemag.org)
  • Here, Arabidopsis thaliana CYCLIN-DEPENDENT KINASE G2 (CDKG2) was shown to act as a negative regulator of the salinity stress response, as well as being involved in the control of flowering time. (deepdyve.com)
  • Kinases regulate many essential cellular processes. (thefreedictionary.com)
  • This is the first demonstration of interaction between a herpesviral CDK ortholog and cellular cyclins. (mdpi.com)
  • Cell and organ growth are profoundly dependent on protein production, a process that provides the building blocks for new cellular components. (plantphysiol.org)
  • Wang, Mei 2015-05-07 00:00:00 Cyclin-dependent protein kinases are involved in many crucial cellular processes and aspects of plant growth and development, but their precise roles in abiotic stress responses are largely unknown. (deepdyve.com)
  • CDK8 and cyclin C associate with the mediator complex and regulate transcription by several mechanisms. (wikipedia.org)
  • These Cdk/cyclin complexes reportedly regulate each step of the cell cycle. (merckmillipore.com)
  • Kinases are used extensively to transmit signals and regulate complex processes in cells. (wikipedia.org)
  • Wee1 family protein kinases that inhibit Cdc2 during the G 2 phase of the cell cycle must be down-regulated at the onset of mitosis. (pnas.org)
  • The weel kinase phosphorylated by cdc2 kinase also bound to 14-3-3 zeta ptotein. (nii.ac.jp)
  • Further, cyclin B/cdc2 kinase, weel kinase and 14-3-3 zeta ptotein form a complex. (nii.ac.jp)
  • Publications] Nagai,Y.: 'Ubiquitin-activating enzyme,E1, is phosphorylated in mammalidn cells by the protein kinase cdc2. (nii.ac.jp)
  • Conversely, DNA damage after CHK1 inhibition is highly dependent on CDC25A. (rupress.org)
  • Conclusions -p27 Kip1 and p21 Cip1 are potent inhibitors of VSMC growth compared with p16 Ink4 because of their different molecular mechanisms of cyclin-dependent kinase inhibition in the G 1 phase of the cell cycle. (ahajournals.org)
  • In this article we report that stable short hairpin RNA-mediated cortactin knockdown in the 11q13-amplified cell line FaDu led to increased expression of the Cip/Kip cyclin-dependent kinase inhibitors (CDKIs) p21(WAF1/Cip1), p27(Kip1), and p57(Kip2) and inhibition of S-phase entry. (garvan.org.au)
  • We looked for but did not obtain strong evidence for cyclin specificity in the use of different mechanisms to control rereplication: both the S-phase cyclin Clb5 and the mitotic cyclins Clb1-4 were inferred to be capable of imposing ORC-based and MCM-based controls. (genetics.org)
  • Clb6-dependent toxicity is also relieved when early accumulation of mitotic cyclins is allowed to impose rereplication controls. (genetics.org)
  • Encodes a member of a plant specific family of cyclin dependent kinases. (nih.gov)
  • The pS123 not only directly interacted with basic residues in the WD40 repeat domain of β-TrCP but also primed phosphorylation by two independent protein kinases, Plk1 and CK2 (formerly casein kinase 2), to create two phosphodegrons on Wee1A. (pnas.org)
  • Casein kinase 1 (CK1) was identified as a principal 95 matrix binding protein in Plasmodium falciparum, Leishmania mexicana, Toxoplasma gondii and Trypanosoma cruzi. (lancs.ac.uk)
  • Inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinases, such as erlotinib and gefitinib, have not been very effective in the treatment of breast cancer although many breast cancer cells express EGFR. (aacrjournals.org)
  • Expression of phosphorylated (p-)tyrosine, p-Akt, phosphorylated extracellular signal-regulated kinase (p-ERK) 1/ERK2 (p42/p44), and p27 after treatment of erlotinib was not associated with erlotinib sensitivity. (aacrjournals.org)
  • Recent genetic studies indicate that mutations of Cdkl family kinases are associated with neurodevelopmental and neuropsychiatric disorders in humans. (frontiersin.org)
  • Mutations in kinases that lead to a loss-of-function or gain-of-function can cause cancer and disease in humans, including certain types of leukemia and neuroblastomas, glioblastoma, spinocerebellar ataxia (type 14), forms of agammaglobulinaemia, and many others. (wikipedia.org)
  • Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. (curehunter.com)
  • Because it is a strong, tight inhibitor of several G1 cyclin/CDK complexes, this protein is a negative regulator of cell proliferation. (cags.org.ae)
  • Here, we have identified the cyclin-dependent kinase inhibitor p27 Kip1 as a critical regulator of the CD8 T-cell homeostasis at all phases of the T-cell response to an acute viral infection in mice. (asm.org)
  • A putative DNA replication origin has been identified in close proximity of INK4/Arf locus that appears to transcriptionally repress p16 in a manner dependent on CDC6 . (atlasgeneticsoncology.org)
  • Altered prostatic epithelial proliferation and apoptosis, prostatic development and serum testosterone in mice lacking cyclin-dependent kinase inhibitors," Biology of Reproduction 73(5): 951-958. (thefreedictionary.com)
  • While these animals were found to have deficiencies in hippocampal-dependent spatial learning and alterations in in vitro synaptic plasticity, interpretation of these phenotypes is complicated as a result of the changes in the gross anatomy. (frontiersin.org)
  • Recombinat 14-3-3 zeta was demonstrated to bind to weel kinase in vitro. (nii.ac.jp)
  • The report provides a competitor evaluation in the field of synthetic molecules targeting polo-like kinase 1 (Plk-1), cyclin-dependent kinase (CDK) or aurora kinase for treatment of cancer as of September 2011. (thefreedictionary.com)
  • The regulatory region is subject to differential phosphorylation at non-glycine residues within this motif, making this site subject to Wee1 and/or Myt1 inhibitory kinase phosphorylation and Cdc25 de-phosphorylation in mammals. (wikipedia.org)
  • Thus, this hinge region, which can vary in length slightly between CDK type and CDK-cyclin complex, connects essential regulatory regions of the CDK by connecting these lobes, and plays key roles in the resulting structure of CDK-cyclin complexes by properly orienting ATP for easy catalysis of phosphorylation reactions by the assembled complex. (wikipedia.org)
  • CDK4 is a member of the cyclin-dependent kinase family. (wikipedia.org)
  • Belongs to the cdkn2 cyclin-dependent kinase inhibitor family. (atlasgeneticsoncology.org)
  • p34Cdc2 kinase family members are known to be essential for eukaryotic cell cycle control. (antibodies-online.com)
  • These findings suggest that Cdkl2 is involved in cognitive function and provide in vivo evidence for the function of Cdkl family kinases expressed in terminally differentiated neurons in mice. (frontiersin.org)
  • Each Cdk is thought to be regulated by its transient association with one or more members of the cyclin family. (merckmillipore.com)
  • Kinases are part of the larger family of phosphotransferases. (wikipedia.org)
  • Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. (mdpi.com)
  • However, other studies in budding and fission yeasts suggest that recombination is not absolutely dependent on premeiotic DNA replication (e.g. (pubmedcentralcanada.ca)
  • In addition, once-per-cell-cycle replication is enforced by cyclin-Cdk-dependent phosphorylation of the prereplicative complex (pre-RC) components Mcm2-7, Cdc6, and Orc1-6. (genetics.org)
  • Control of DNA replication by cyclin-dependent kinases in development. (inserm.fr)
  • Targeting cyclins and cyclin-dependent kinases in cancer: lessons from mice, hopes for therapeutic applications in human. (thefreedictionary.com)
  • Vi beskriver også rensning protokoller, der giver meget rene og homogen protein præparater egnet til kinase assay, og et bindende assay funktionelle verifikation af de identificerede fosforylering websteder, som sonder samspillet mellem en klassisk nukleare lokalisering signal (cNLS) og dens nukleare transport receptor karyopherin α. (jove.com)
  • Western blotting was used to measure cyclin-dependent kinase (CDK) inhibitors p21 and p27 that arrest cell cycle. (thefreedictionary.com)
  • Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. (biomedsearch.com)
  • A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. (harvard.edu)