AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesDisciplines and OccupationsInformation Science
Cyclin-Dependent KinasesCyclin-Dependent Kinase 2Cyclin D1Cyclin ACyclin ECyclinsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase Inhibitor p27CDC2-CDC28 KinasesCell CycleCyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent Kinase 5Cell Cycle ProteinsCyclin BCyclin CProtein-Serine-Threonine KinasesCDC2 Protein KinaseCyclin DG1 PhaseCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor ProteinsCyclin D3Cyclin B1Retinoblastoma ProteinPhosphorylationCyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p57Tumor Suppressor ProteinsS PhaseProtein Kinase InhibitorsCyclin D2Cyclin A1Microtubule-Associated ProteinsProtein KinasesCell ProliferationPurinesCell DivisionApoptosisProto-Oncogene ProteinsE2F1 Transcription FactorCyclin A2Phosphatidylinositol 3-KinasesCyclin GCell Line, TumorTumor Cells, CulturedTumor Suppressor Protein p53MitosisCyclin G1MAP Kinase Signaling SystemTranscription Factor DP1Signal TransductionCells, CulturedBlotting, WesternEnzyme InhibitorsG2 PhaseE2F Transcription FactorsTransfectionCalcium-Calmodulin-Dependent Protein KinasesMutationProliferating Cell Nuclear AntigenMolecular Sequence DataCell LineDNA-Binding ProteinsCarrier ProteinsNuclear ProteinsBase SequenceRNA, MessengerProtein Kinase CTranscription Factorssrc-Family KinasesImmunohistochemistryReverse Transcriptase Polymerase Chain ReactionDNA DamageAntineoplastic AgentsAmino Acid Sequencep38 Mitogen-Activated Protein KinasesCyclic AMP-Dependent Protein KinasesCyclin B2Mitogen-Activated Protein Kinase 1Protein BindingEnzyme ActivationGene Expression RegulationTranscription, GeneticCyclin TMitogen-Activated Protein Kinase Kinasesp21-Activated KinasesMitogen-Activated Protein Kinase 3JNK Mitogen-Activated Protein KinasesProtein-Tyrosine KinasesCyclin HCyclin G2KineticsCalcium-Calmodulin-Dependent Protein Kinase Type 2MAP Kinase Kinase KinasesRecombinant Fusion Proteins3T3 CellsCreatine KinaseModels, BiologicalCalciumCasein Kinase II
InhibitorsCDKsCDKN2APhosphorylationINK4aRibociclibProtein kinasesCDK6GeneTyrosine kinasesAbemaciclibSerinePeptidesPathwayPhosphorylateCdc2InhibitionEnzymesSubstrateRetinoblastomaP16INK4aProgressionMutationComplexesPalbociclibMethodsActivityCDKN1BAminoCancerMetastaticReplicationRegulatorChemotherapyFamilyComplexFoundHuman
Inhibitors20
  • 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)
  • Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors. (rcsb.org)
  • Prior treatment with abemaciclib or any cyclin-dependent kinase (CDK) 4 & 6 inhibitors. (dana-farber.org)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Slamon also led the discovery program that found that cyclin-dependent kinase inhibitors are effective in treating hormone receptor positive breast cancer. (nepalnews.com)
  • Working with Huang and others, he also showed that SMARCA4 loss in SCCOHT causes cyclin D1 deficiency, and hence, susceptibility to CDK4/6 inhibitors. (cancernetwork.com)
  • Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). (her2support.org)
  • Scientific findings from the first BEAUTY study indicate that CDK 4 and 6 inhibitors may prevent cancer from becoming metastatic. (mayo.edu)
  • The INK and CIP/KIP families of cyclin dependent kinase inhibitors (CDKis) protect cells from oncogenic signals-initiated cellular transformation. (sigmaaldrich.com)
  • The benefits of giving CDK 4/6 inhibitors for early- stage , hormone receptor -positive breast cancer remain unclear after two studies, monarchE and PENELOPE-B, presented conflicting results during the San Antonio Breast Cancer Symposium on Wednesday. (lbbc.org)
  • CDK 4/6 inhibitors are targeted therapies that block the function of certain proteins, cyclin-dependent kinases 4 and 6, in cancer cells. (lbbc.org)
  • Since then, two other CDK 4/6 inhibitors have been approved and all three have become standard care for people with that diagnosis . (lbbc.org)
  • While an important treatment for people with metastatic, hormone receptor-positive breast cancer, researchers have not yet found a role for CDK 4/6 inhibitors in early-stage breast cancer treatment. (lbbc.org)
  • The activity of this kinase first appears in mid-G1 phase, which is controlled by the regulatory subunits including D-type cyclins and members of INK4 family of CDK inhibitors. (cancerindex.org)
  • 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)
  • A prior period of treatment with aromatase inhibitors or fulvestrant for up to 28 days from the CDK 4/6-inhibitor initiation is allowed. (who.int)
  • 5. Adjuvant treatment with CDK 4/6-inhibitors is allowed provided a disease-free interval from treatment end >12 months. (who.int)
  • 8. Adequate organ function as defined in the summary of product characteristics (SmPC) for the CDK 4/6-inhibitors that is planned to be used. (who.int)
  • 4/6-inhibitors. (who.int)
  • 2. Contraindications according to SmPC for the CDK 4/6-inhibitors that is planned to be used. (who.int)
CDKs3
CDKN2A7
  • 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)
  • In particular, the p16/cyclin-dependent kinase inhibitor 2A (CDKN2A) gene located on chromosomal region 9p21 frequently is altered in several types of cancer. (iiarjournals.org)
  • The tumor suppressor gene p16/cyclin-dependent kinase inhibitor-2A (CDKN2A) is located within the chromosomal region 9p21 and encodes a cell-cycle protein that is an inhibitor of cyclin-dependent kinases (CDK)-4 and -6. (iiarjournals.org)
  • also known as CDK4I, Cyclin-dependent kinase 4 inhibitor A, Multiple tumor suppressor 1, MTS-1, p16-INK4, p16-INK4a, p16INK4A) is encoded by the CDKN2A (also known as CDKN2, MTS1) gene (Gene ID 1029) in human. (sigmaaldrich.com)
  • Five out of eight cases (63%) displayed cyclin-dependent kinase inhibitor 2A (CDKN2A) abnormalities, either copy number loss (n = 4) or truncating mutations (n = 1). (lu.se)
  • BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. (lu.se)
  • 0001). Families with breast cancer also had a propensity for multiple melanomas in females, suggesting that a sex-dependent factor may modify the phenotypic expression of CDKN2A alterations. (lu.se)
Phosphorylation7
  • This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (wikipedia.org)
  • Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. (rcsb.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)
  • 18-20 p16 INK4a shares functional similarities with p53 in that it blocks progression through the cell cycle at G1/S by inhibiting CDK 4/6 mediated phosphorylation of Rb. (bmj.com)
  • As a result, it negatively regulates cyclin-D-dependent phosphorylation of the retinoblastoma (pRb) gene product, thus blocking cell-cycle progression from G 1 -to S-phase ( 2 - 4 ). (iiarjournals.org)
  • Activation of CDK4 requires binding of a D-type Cyclin and phosphorylation of Thr172 by the CAK kinase complex. (rndsystems.com)
INK4a2
  • This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D1, Cdk4, INK4a and INK4b, pRb etc. (nih.gov)
  • 13 p16 INK4a is a cyclin dependent kinase inhibitor that is frequently mutated or deleted in many human cancer cell lines 14-16 and some sporadic malignancies, including sarcomas, breast cancer, leukaemia, and brain tumours, which are all component tumours of LFS. (bmj.com)
Ribociclib2
  • Previously, Slamon and researchers at the Jonsson Cancer Center demonstrated that adding ribociclib, a cyclin-dependent kinase inhibitor, to the standard hormone therapy improves overall survival in both premenopausal and postmenopausal women with metastatic HR positive/HER2 negative breast cancer. (nepalnews.com)
  • The new results come from an interim analysis of the phase 3 randomized NATALEE trial , which is comparing maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone. (medscape.com)
Protein kinases1
CDK62
Gene3
  • 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)
  • MEN 4 is caused by an inactivating mutation of the CDKN1B gene, which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. (msdmanuals.com)
Tyrosine kinases1
  • We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
Abemaciclib3
  • Abemaciclib, a CDK 4 and 6 inhibitor, is approved by the U.S. Food and Drug Administration for the treatment of hormone receptor positive, HER2 negative breast cancer. (mayo.edu)
  • The maker of abemaciclib (Verzenio) announced in June that monarchE is the first and, so far, only study to find that adding a CDK 4/6 inhibitor to early-stage breast cancer treatment lowered the risk of breast cancer coming back. (lbbc.org)
  • Participants were randomly assigned to get the CDK 4/6 inhibitor abemaciclib for up to 2 years alongside hormonal therapy , or to get hormonal therapy alone. (lbbc.org)
Serine1
  • Additionally, ACT‑3 significantly increased autophagic cell death by inhibiting the serine‑threonine kinase/mammalian target of the rapamycin pathway. (iasp-pain.org)
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)
Pathway3
  • The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. (nih.gov)
  • Thus, the activated ERK pathway played an important role in cell cycle arrest and apoptosis via ERK‑dependent induction of p21 in MCF‑7 cells. (iasp-pain.org)
  • Defects of the retinoblastoma protein (pRb)/cyclin-D1/p16 pathway have been shown to play a critical role in the development of human malignancies. (iiarjournals.org)
Phosphorylate2
  • 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)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
Cdc21
Inhibition3
  • Cyclin-dependent kinase 4/6 (CDK4/6) inhibition, a treatment used with some breast cancers, might also prove effective against tumor suppressor SMARCA4 ( BRG1 ) mutation-harboring lung cancers and a rare, aggressive form of SMARCA4 mutation-driven ovarian cancer, suggest preclinical findings reported in a pair of papers in Nature Communications . (cancernetwork.com)
  • Anticancer effects of the HDAC inhibitor, 3β,6β‑dihydroxyurs‑12‑en‑27‑oic acid, in MCF‑7 breast cancer cells via the inhibition of Akt/mTOR pathways. (iasp-pain.org)
  • The Potential for Selective Cyclin-Dependent Kinase 4/6 Inhibition in the Therapy for Head and Neck Squamous Cell Carcinoma. (cdc.gov)
Enzymes1
  • These drugs work by blocking the activity of cyclin-dependent kinase 4/6 enzymes, which promote cell division and cancer growth. (nepalnews.com)
Substrate3
Retinoblastoma1
P16INK4a1
  • The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. (wikipedia.org)
Progression2
  • It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (wikipedia.org)
  • CDK4 may be useful as a prognostic marker for hepatocellular carcinoma and its kinase activity has been reported to promote the progression of T cell acute lymphoblastic leukemia. (rndsystems.com)
Mutation2
  • Tagrisso, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is the first medication approved to treat patients with non-small cell lung cancer (NSCLC) who develop resistance to first-line TKIs due to the development of the EGFR T790M mutation. (pharmacytimes.com)
  • Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. (rcsb.org)
Complexes1
  • Cyclin D-CDK4 complexes are major integrators of various mitogenic and antimitogenic signals. (wikipedia.org)
Palbociclib2
  • Background/Aim: Palbociclib was the first cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved worldwide. (iiarjournals.org)
  • The PENELOPE-B trial looked at adding the CDK 4/6 inhibitor palbociclib (Ibrance) to hormonal therapy for early-stage, hormone receptor-positive, HER2-negative breast cancer that showed a high risk of recurring. (lbbc.org)
Methods1
  • Modern molecular methods, including genetic markers, cytokines, proliferation indexes, and cyclins, are all undergoing study to help determine which atypical moles may progress to melanoma, although no single marker has been determined. (medscape.com)
Activity5
  • Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. (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)
  • The anticancer activity of 3β,6β‑dihydroxyurs‑12‑en‑27‑oic acid (ACT‑3), a major component isolated from , has not yet been investigated in detail. (iasp-pain.org)
  • ACT‑3 inhibited total HDAC activity in a dose‑dependent manner. (iasp-pain.org)
  • One of the more predominant mutational signatures was intimately coupled to the activity of Apolipoprotein B mRNA-editing enzyme, the catalytic polypeptide-like (APOBEC) family of cytidine deaminases implied in kataegis, a focal hypermutation phenotype, which was observed in 4/8 (50%) cases. (lu.se)
CDKN1B1
  • Because of the clinical similarity between MEN 1 and MEN 4, patients with this constellation of symptoms should undergo genetic testing utilizing a panel of genes that includes both MEN1 and CDKN1B . (msdmanuals.com)
Amino1
  • Cyclin-dependent Kinase 4 (CDK4) is a 303 amino acid (aa) member of the Ser/Thr kinase family with a predicted molecular weight of 33.7 kDa. (rndsystems.com)
Cancer6
  • For example in colorectal cancer, long-term remission of oligometastatic lung or liver disease is achievable in a subgroup of patients and this strategy is part of established guidelines [ 4 ]. (springer.com)
  • 4-6 Families adhering to the classical definition of the syndrome include those in which one subject, usually the proband, is diagnosed with a sarcoma before 45 years of age, and has a first degree relative with cancer before 45 years of age, and another first or second degree relative in the same parental lineage with any cancer diagnosed under 45 years of age or with sarcoma at any age. (bmj.com)
  • Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. (rcsb.org)
  • 4. History of any other cancer (except of non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years. (who.int)
  • International journal of cancer 2022 4 151 (6): 957-966. (cdc.gov)
  • European journal of cancer (Oxford, England : 1990) 2022 4 168 34-40. (cdc.gov)
Metastatic1
  • In order to cure metastatic disease, several approaches are imaginable: (1) locoregional treatment of the primary tumor and all metastatic sites, (2) tumor eradication by excellent systemic anticancer therapy, (3) long-term immunologic tumor control induced by immunotherapy or (4) the combination of these approaches. (springer.com)
Replication1
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
Regulator1
Chemotherapy1
  • BCSCs can develop into many cell types and repopulate heterogeneous tumors following conventional chemotherapy or radiotherapy [ 4 , 6 ]. (hindawi.com)
Family3
  • CDK4 is a member of the cyclin-dependent kinase family. (wikipedia.org)
  • CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
  • Multiple endocrine neoplasia type 4: a new member of the MEN family. (msdmanuals.com)
Complex1
  • The CDK4/Cyclin D complex is also negatively regulated by p21/CIP1/CDKN1A and p27/Kip1. (rndsystems.com)
Found1
Human1
  • Orthologous to human CDK2AP1 (cyclin dependent kinase 2 associated protein 1). (nih.gov)