CDKsInhibitorsPhosphorylationSerine-threonCdk2ProgressionInhibitionChem BiolComplexesPeptidesRegulateProtein KinasesGeneRegulatesProteinsCellularSelectivitySubstrateMechanismTranscriptionalCdc2Cdk2ap1RegulatoryOvarian cancerCaseinMitoticTargetsEnzymePromotesCellSpecificityProliferationActivationNuclear
CDKs6
- Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (nature.com)
- Aberrant control of cyclin-dependent kinases (CDKs) is a central feature of the molecular pathology of cancer. (rcsb.org)
- Cyclin-dependent kinases (CDKs), are members of the serine-threonine protein kinase family and are responsible for taking control of cell cycle regulation in eukaryotic cells. (spandidos-publications.com)
- CDKs show their action by interacting with cyclins and different CDK-cyclin complexes regulate the cell cycle in the G1, S and G2/M phases ( 1 ). (spandidos-publications.com)
- Flavopiridol is a synthetic flavone that has been postulated to be an inhibitor of cyclin-dependent kinases (CDKs) (Schmerwitz et al. (researchsquare.com)
- A relatively well understood example is the network that controls progression of the cell cycle, where cyclin-dependent kinases (CDKs) couple with various cyclins over the cell cycle to regulate critical processes [ 2 - 4 ]. (biomedcentral.com)
Inhibitors9
- It is regulated by Cyclin D. Ribociclib are US FDA approved CDK4 and CDK6 inhibitors for the treatment of estrogen receptor positive/ HER2 negative advanced breast cancer. (wikipedia.org)
- Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
- A screen of 72 inhibitors against 456 human kinases. (guidetopharmacology.org)
- 2018) Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors. (guidetopharmacology.org)
- 2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. (guidetopharmacology.org)
- Cyclin-dependent kinase (cdk) inhibitors have the potential to induce growth arrest and apoptosis in cancer cells. (omecamtivmecarbilactivator.com)
- Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
- SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)
- Palbociclib and ribociclib are cyclin-dependent kinases (CDK) 4, 6 inhibitors indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. (medscape.com)
Phosphorylation10
- This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (wikipedia.org)
- Here we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5 and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28) substrates. (nature.com)
- Although we did not identify any highly Clb2-specific substrates, we found that Clb2-Cdk1 possessed higher intrinsic kinase activity than Clb5-Cdk1, enabling efficient phosphorylation of a broad range of mitotic Cdk1 targets. (nature.com)
- We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases. (mdanderson.org)
- Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. (jefferson.edu)
- Cellular studies with O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino) purine demonstrated inhibition of MCF-7 cell growth and target protein phosphorylation, consistent with CDK1 and CDK2 inhibition. (rcsb.org)
- CVT-313 treatment reduced cdk2-mediated phosphorylation of the retinoblastoma gene product (Rb) on T821, but did not affect cyclin D-cdk4/6-mediated Rb phosphorylation on S807/811. (omecamtivmecarbilactivator.com)
- A cyclin-dependent kinase-mediated phosphorylation switch of disordered protein condensation. (nih.gov)
- The mTOR signaling complex 1 (mTORC1) helps maintaining protein synthesis through phosphorylation of at least two direct targets, eukaryotic initiation factor (eIF) 4E-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks) [ 3 ] that regulate the activity of EIF4F, a heterotrimeric complex required for the cap-dependent ribosome recruitment phase of translation initiation. (biomedcentral.com)
- The various markers that enable assessment of the progression of preneoplastic lesions to spindle cell carcinoma include the p16 protein, which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). (bvsalud.org)
Serine-threon1
- Akt (PKB) is a serine threonine protein kinase downstream of the phosphoinositide 3-kinase (PI3K) pathway. (biomedcentral.com)
Cdk22
- The work represents the first successful iterative synthesis of a potent CDK inhibitor based on the structure of fully activated CDK2-cyclin A. Furthermore, the potency of O(6)-cyclohexylmethyl-2-(4'- sulfamoylanilino)purine was both predicted and fully rationalized on the basis of protein-ligand interactions. (rcsb.org)
- The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. (cancerindex.org)
Progression6
- It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
- Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (jefferson.edu)
- 4 While studies have historically noted an increased overall survival (OS) in patients with MM who receive ASCT, the recent DETERMINATION trial demonstrates only progression-free survival (PFS) benefit in patients with MM randomized to receive triplet therapy (lenalidomide, bortezomib, and dexamethasone followed by lenalidomide maintenance) with or without ASCT. (haematologica.org)
- Activation of the Ras-MAPK-Erk and PI3K-Akt-mTOR pathways both culminate in activation of transcriptional programs, as well as cyclin dependant kinases, that lead to progression through the cell cycle. (biomedcentral.com)
- Current evidence indicates that, through either of these pathways, HER2 signaling can regulate c-Myc, a multifunctional transcription factor involved in cell cycle progression (see [ 4 ] and references therein). (biomedcentral.com)
- Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cyclin-CDK complex, arresting cell cycle. (biomedcentral.com)
Inhibition3
- Cyclin D1 regulates cellular migration through the inhibition of thrombospondin 1 and ROCK signaling. (jefferson.edu)
- New anticancer therapy strategies refer to the inhibition of CDK-cyclin complexes as an important target to prevent uncontrolled proliferation and induce apoptosis in cancer cells ( 2 ). (spandidos-publications.com)
- This results in inhibition of NFκB activity and the NFκB-dependent expression of anti-apoptotic genes of the Bcl-2 family [ 15 ]. (biomedcentral.com)
Chem Biol2
- Chem Biol , 17 (11): 1241-9. (guidetopharmacology.org)
- Nat.Chem.Biol. (rndsystems.com)
Complexes4
- Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. (wikipedia.org)
- Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
- A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
- The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.com)
Peptides1
- Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)
Regulate1
- Cyclin-dependent kinases regulate the antiproliferative function of Smads. (idrblab.net)
Protein Kinases2
- Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
- Protein kinases are ubiquitous components of cellular signalling networks [ 1 ]. (biomedcentral.com)
Gene5
- 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)
- Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a), CDKN2A and Rb were all found to be associated with tumorigenesis of a variety of cancers. (wikipedia.org)
- The p19ink4d cyclin dependent kinase inhibitor gene is altered in osteosarcoma. (biomedcentral.com)
- Cyclin-G-associated kinase (GAK) , a PD susceptibility gene identified through genome-wide association studies (GWAS), is a ubiquitous serine/threonine kinase involved in clathrin uncoating (see Drosophila Clathrin heavy chain ), though its PD-related function remains elusive. (sdbonline.org)
Regulates2
- NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-beta (transforming growth factor-beta) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-beta type I receptor. (idrblab.net)
- The protein kinase Akt also known as PKB, regulates multiple cellular functions including proliferation, survival, and growth during embryonic development and adult tissue homeostasis [ 1 - 5 ]. (biomedcentral.com)
Proteins3
- The PCM is an ordered lattice that anchors a large number of microtubule (MT)-associated proteins, many of which bear putative coiled-coil domains, a tertiary structure known to facilitate protein-protein interactions [ 4 ]. (biomedcentral.com)
- We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
- This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS. (lookformedical.com)
Cellular2
- The MTOC is responsible to direct the assembly and the orientation of MTs and to control MT-dependent processes such as trafficking of cytoplasmic vesicles and orientation of cellular organelles. (biomedcentral.com)
- Vinca alkaloids are also thought to increase apoptosis by increasing concentrations of p53 (cellular tumor antigen p53) and p21 (cyclin-dependent kinase inhibitor 1) and by inhibiting Bcl-2 activity. (smpdb.ca)
Selectivity1
- Purvalanol is a purine-derived CDKI that binds with a high selectivity and competitively to the ATP binding side of CDK1/2 and leads to G2/M cell cycle arrest ( 4 ). (spandidos-publications.com)
Substrate2
- Schulman, B. A., Lindstrom, D. L. & Harlow, E. Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. (nature.com)
- Finally, we examine co-clustering of the CDK consensus motifs with the 'cy' or RXL motif [ 17 ], which is known to be important in determining which CDK-cyclin complex will phosphorylate a given substrate. (biomedcentral.com)
Mechanism1
- Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. (jefferson.edu)
Transcriptional2
- Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (wikipedia.org)
- Smad3 allostery links TGF-beta receptor kinase activation to transcriptional control. (idrblab.net)
Cdc21
- Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)
Cdk2ap12
- Orthologous to human CDK2AP1 (cyclin dependent kinase 2 associated protein 1). (nih.gov)
- Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. (cancerindex.org)
Regulatory2
- The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. (wikipedia.org)
- cyclin-dependent kinase 5, regulatory. (wikigenes.org)
Ovarian cancer1
- Pai HC, Kumar S, Shen CC, Liou JP, Pan SL, Teng CM. MT-4 suppresses resistant ovarian cancer growth through targeting tubulin and HSP27. (jefferson.edu)
Casein1
- Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger its nuclear localization. (idrblab.net)
Mitotic1
- Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
Targets1
- Targets of the cyclin-dependent kinase Cdk1. (nature.com)
Enzyme2
- inositol-requiring enzyme 1 (IRE1α), PRKR-like ER kinase (PERK) and activating transcription factor-6 (ATF-6). (spandidos-publications.com)
- Choline kinase (ChoK), the enzyme responsible for the generation of phosphorylcholine (PCho) from its precursor choline, is the first enzyme in the Kennedy pathway that renders phosphatidylcholine as its final product. (aacrjournals.org)
Promotes1
- Schindler K, Benjamin KR, Martin A, Boglioli A, Herskowitz I, Winter E. The Cdk-activating kinase Cak1p promotes meiotic S phase through Ime2p. (jefferson.edu)
Cell6
- Nature Cell Biol. (nature.com)
- Mol Cell Biol. (jefferson.edu)
- Cyclin-dependent kinase 2-associating protein 1 commits murine embryonic stem cell differentiation through retinoblastoma protein regulation. (nih.gov)
- Despite management by a fat-restricted diet and peripheral infusion on postoperative day 4, chyle from the drainage remained high, with a TG of 257 mg/dL, a cell count of 525/mm3(70% lymphocytes), and a postoperative drainage volume of over 500 mL per day. (bvsalud.org)
- J Cell Biol (2015) 208 (4): 387-389. (rupress.org)
- Functional loss of p16 may lead to uncontrolled cell proliferation 3,4 . (bvsalud.org)
Specificity1
- Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
Proliferation1
- G?ller M, Toualbi-Abed K, Legrand A, Michel L, Mauviel A, Bernuau D, Daniel F. c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1. (jefferson.edu)
Activation1
- Choline kinase (ChoK) is increased in human mammary tumors with high incidence, and this activation is associated with clinical variable indicators of greater malignancy. (aacrjournals.org)
Nuclear2
- Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. (wikipedia.org)
- during pachytene, telomeres disperse, yet remain attached to the nuclear envelope and are subject to actin-dependent pulling forces ( Z ickler and K leckner 1998 ). (biorxiv.org)