• Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. (escholarship.org)
  • Studies using siRNA-mediated knockdown and/or selective CDK inhibitors show that P-TEFb plays a functional role in activation of a subset of NFκB-dependent targets and all STAT3-dependent genes studied to date. (utmb.edu)
  • We studied the roles of cyclin-dependent kinase inhibitors Cdkn2a and Cdkn2b, known as cellular stress-related senescence markers, in N-methyl-d-aspartate (NMDA)-induced RGC death. (elsevierpure.com)
  • Screening through Lead Optimization of High Affinity, Allosteric Cyclin-Dependent Kinase 2 (CDK2) Inhibitors as Male Contraceptives That Reduce Sperm Counts in Mice. (expasy.org)
  • We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. (nih.gov)
  • Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
  • [ 2 ] Options for second-line therapy in patients with relapsed/refractory disease include chemotherapy-free regimens with biologic targeted agents such as covalent Bruton tyrosine kinase (BTK) inhibitors, lenalidomide,venetoclax, and chimeric antigen receptor (CAR) T-cell therapy. (medscape.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)
  • The protein encoded by this gene is a neuron-specific activator of CDK5 kinase. (nih.gov)
  • It associates with CDK5 to form an active kinase. (nih.gov)
  • This protein and neuron-specific CDK5 activator CDK5R1/p39NCK5A both share limited similarity to cyclins, and thus may define a distinct family of cyclin-dependent kinase activating proteins. (nih.gov)
  • Inhibitor-1, the first identified endogenous inhibitor of protein phosphatase 1 (PP-1), was previously reported to be a substrate for cyclin-dependent kinase 5 (Cdk5) at Ser 67 . (elsevierpure.com)
  • Thus, inhibitor-1 serves as a critical junction between kinase- and phosphatase-signaling pathways, linking PP-1 to not only PKA and calcineurin but also Cdk5. (elsevierpure.com)
  • Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that has been implicated in learning, synaptic plasticity, neurotransmission, and numerous neurological disorders. (elsevierpure.com)
  • In this study, we examined the expression and subcellular localization of cyclin-dependent kinase 5 (Cdk5), cyclin D1, and cyclin E in Leydig and Sertoli cell lines that were cultured with 7.5, 1.0, 0.5, or 0% serum (mixture of a 2:1 ratio of horse serum and fetal bovine serum) and in the developing rat testis to verify the possible functions of Cdk5, cyclin D1, and cyclin E in the testis. (elsevierpure.com)
  • The abundance of Cdk5 and cyclin E in the Leydig cell line, TM3, was significantly reduced at low serum concentrations. (elsevierpure.com)
  • In contrast, serum concentration had no effect on Cdk5 and cyclin E levels in the Sertoli cell line, TM4. (elsevierpure.com)
  • The kinase activity of Cdk5 in TM3 and TM4 cells that were cultured at various serum concentrations coincided with the levels of Cdk5 expression. (elsevierpure.com)
  • Immunohistochemical staining for Cdk5 and cyclin E revealed nuclear and cytoplasmic distribution, both in TM3 and TM4 cells. (elsevierpure.com)
  • Immunohistochemical localization of Cdk5, cyclin D1, and cyclin E in 1-week- old and adult rat testes revealed expression in both Leydig and Sertoli cells. (elsevierpure.com)
  • Ashok B. Kulkarni, Ph.D., has spent years studying a protein called cyclin-dependent kinase 5 (Cdk5). (medlineplus.gov)
  • Cyclin-CDK complexes phosphorylate substrates appropriate for the particular cell cycle phase. (wikipedia.org)
  • Furthermore, cyclin binding determines the specificity of the cyclin-CDK complex for particular substrates. (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)
  • Spy1 lacks the cyclin-binding site that mediates p27 and substrate affinity, explaining why Cdk-Spy1 is poorly inhibited by p27 and lacks specificity for substrates with cyclin-docking sites. (escholarship.org)
  • Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. (biomedcentral.com)
  • Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. (nih.gov)
  • only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. (wikipedia.org)
  • Substrate specificity of S cyclins is imparted by the hydrophobic batch (centered on the MRAIL sequence), which has affinity for substrate proteins that contain a hydrophobic RXL (or Cy) motif. (wikipedia.org)
  • We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
  • Reversible phosphorylation of proteins by kinases and phosphatases plays a key regulatory role in several eukaryotic cellular functions including the control of the division cycle. (bibbase.org)
  • article{meszaros_multiple_2000, title = {Multiple cyclin-dependent kinase complexes and phosphatases control {G2}/{M} progression in alfalfa cells}, volume = {43}, issn = {1573-5028}, url = {https://doi.org/10.1023/A:1006412413671}, doi = {10/cb64mn}, abstract = {Reversible phosphorylation of proteins by kinases and phosphatases plays a key regulatory role in several eukaryotic cellular functions including the control of the division cycle. (bibbase.org)
  • Cyclin-dependent kinase inhibitor p27Kip1 expression and interaction with other cell cycle-associated proteins in mammary carcinoma. (ox.ac.uk)
  • 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)
  • Phosphorylation by CDK-activating kinase (CAK) at Thr 161 on the T-loop increases the complex activity. (wikipedia.org)
  • Full kinase activity requires an activating phosphorylation on a threonine adjacent to the CDK's active site. (wikipedia.org)
  • The identity of the CDK-activating kinase (CAK) that performs this phosphorylation varies across the model organisms. (wikipedia.org)
  • In mammalian cells, the activating phosphorylation occurs after cyclin binding. (wikipedia.org)
  • Various kinases and phosphatases regulate their phosphorylation state. (wikipedia.org)
  • Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. (jefferson.edu)
  • Phosphorylation assays also revealed that at least three kinase complexes (Cdc2Ms A/B, D and F) were successively active in G2/M cells after synchronization. (bibbase.org)
  • however tyrosine phosphorylation was indicated in the case of Cdc2Ms A kinase and the p13suc1-bound kinase activity was increased by treatment of this complex with recombinant Drosophila Cdc25. (bibbase.org)
  • In mammalian cells, CDK1, with its partners cyclin A2 and B1, alone can drive the cell cycle. (wikipedia.org)
  • Cyclin B1 and B2 can localize Cdk1 to the nucleus and the Golgi, respectively, through a localization sequence outside the CDK-binding region. (wikipedia.org)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • Previously, we found that eukaryotic initiation factor (eIF) 4A interacts with cyclin dependent kinase A (CDKA), the plant ortholog of mammalian CDK1. (aber.ac.uk)
  • Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. (jefferson.edu)
  • Chromatin immunoprecipitation studies have preliminarily indicated that this recruitment is dependent on CDK enzymatic activity. (utmb.edu)
  • The Cyclin D-Cdk4,6/INK4/Rb/E2F pathway plays a key role in controlling cell growth by integrating multiple mitogenic and antimitogenic stimuli. (nih.gov)
  • This pathway is deregulated in the vast majority of human tumors by genetic and epigenetic alterations that target at least some of its key members such as Cyclin D1, Cdk4, INK4a and INK4b, pRb etc. (nih.gov)
  • United States, Nevada, Las Vegas),DelveInsight's "Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficiency Disorder- Pipeline Insight, 2023" report provides comprehensive insights about 5+ companies and 5+ pipeline drugs in the CDKL5 Deficiency Disorder pipeline landscape. (marketsampler.com)
  • Cyclin-dependent Kinas Like 5 deficiency disorder is a rare developmental encephalopathy (DE) caused by pathogenic variants in the gene cyclin-dependent kinase-like 5 (CDKL5). (marketsampler.com)
  • Most of the known cyclin-CDK complexes regulate the progression through the cell cycle. (wikipedia.org)
  • Cyclin-CDK complexes of earlier cell-cycle phase help activate cyclin-CDK complexes in later phase. (wikipedia.org)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • The p21 family (p21, p27, p28 and p57) can bind to broad range of CDK-cyclin complexes and inhibit their activities. (biomedcentral.com)
  • Lundberg, A. S. & Weinberg, R. A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. (nature.com)
  • The Positive Transcriptional Elongation Factor b (P-TEFb), a heterodimer of CDK9 and Cyclin T1, is widely implicated in control of basal gene expression. (utmb.edu)
  • 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)
  • There is considerable specificity in which cyclin binds with CDK. (wikipedia.org)
  • Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • Interaction between alfalfa mitotic cyclin (Medsa;CycB2;1) and a kinase partner has been reported previously. (bibbase.org)
  • Cyclin D1 regulates cellular migration through the inhibition of thrombospondin 1 and ROCK signaling. (jefferson.edu)
  • The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. (johnshopkins.edu)
  • There was a statistically significant association between the expression of p27 and both cyclin D1 and the retinoblastoma gene product (pRb), corresponding to their close interactions in regulating the G1/S transition in the cell cycle. (ox.ac.uk)
  • The Cyclin-dependent kinase-like 5 Deficiency disorder gene is responsible for creating a protein necessary for normal brain development and function. (marketsampler.com)
  • The molecular consequence of translocation is overexpression of the protein cyclin D1 (coded by the PRAD1 gene located close to the breakpoint). (medscape.com)
  • The present yeast two-hybrid analyses showed differential interaction between defined D-type cyclins and Cdc2Ms kinases functioning in G2/M phases. (bibbase.org)
  • The protein interaction landscape of the human CMGC kinase group. (nature.com)
  • In yeast cells, it occurs before cyclin binding. (wikipedia.org)
  • To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin-dependent kinase complex Bur1/2 as a regulator of telomere length. (johnshopkins.edu)
  • It is the sequential activation and inactivation of cyclin-dependent kinases, through the periodic synthesis and destruction of cyclins, that provides the primary means of cell-cycle regulation. (expasy.org)
  • An INK4 cyclin-dependent kinase inhibitor containing five ANKYRIN-LIKE REPEATS. (childrensmercy.org)
  • We investigated protein levels of the signaling pathway: p35, cyclin-dependent kinase 5, Munc18a, syntaxin 1A and 1B, Munc18-interacting protein 1 and Munc18-interacting protein 2 in Alzheimer's disease cortex and found that this pathway was up-regulated in the Alzheimer's disease parietal and occipital cortex. (eur.nl)
  • Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation. (johnshopkins.edu)
  • 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)
  • Cyclin-dependent kinase 5 and its activator p35 disrupt Munc18a-syntaxin 1 binding, thereby promoting synaptic vesicle fusion during exocytosis. (eur.nl)
  • In addition to direct CDK inhibition, flavopiridol also exhibited other features such as inducing apoptosis in many cancer cell lines, decreasing cyclin D1 concentration, and inhibiting angiogenesis. (usuhs.edu)
  • Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a time- and concentration-dependent manner. (mdpi.com)
  • Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. (hindawi.com)
  • Mutations in either BUR1 cyclin-dependent kinase or the associated BUR2 cyclin resulted in short telomeres. (johnshopkins.edu)
  • cyclin L CDK levels remain relatively constant throughout the cell cycle and most regulation is post-translational. (wikipedia.org)
  • CAK activity is not regulated by known cell-cycle pathways and cyclin binding is the limiting step for CDK activation. (wikipedia.org)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • Localization of Cdc2Ms F kinase to the preprophase band (PPB), the perinuclear ring in early prophase, the mitotic spindle and the phragmoplast indicated a pivotal role for this kinase in mitotic plant cells. (bibbase.org)
  • Localization to the chromocenters is mediated by an N-terminal domain, in addition we find that this domain may be involved in cyclin binding. (uni-bielefeld.de)