• Recently, a series of studies revealed the diagnostic and prognostic value of CDKs (mainly CDK1-7) in different types of human cancer, including oral cancer, medulloblastoma, pancreatic cancer ( 11 - 14 ). (jcancer.org)
  • Cyclins (regulatory subunits) bind to cdks (catalytic subunits) to form complexes that regulate the progression of the cell cycle. (bdbiosciences.com)
  • The main cyclin-cdks complexes formed in vertebrate cells are cyclin D-cdk4 (G0/G1), cyclin E-cdk2 (G1/S), cyclin A-cdk2 (S) and cyclin B1-cdk1 (G2/M). These complexes are regulated by activating and inhibitory phosphorylation events, as well as by interactions with small regulatory proteins including p21 and p27Kip1. (bdbiosciences.com)
  • The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • 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)
  • 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)
  • Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. (proteopedia.org)
  • In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. (proteopedia.org)
  • NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. (proteopedia.org)
  • Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. (proteopedia.org)
  • Zhao J, Kennedy BK, Lawrence BD, Barbie DA, Matera AG, Fletcher JA, Harlow E. NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. (proteopedia.org)
  • Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (oncotarget.com)
  • Here, we show that cyclin E/Cdk2 phosphorylates and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). (oncotarget.com)
  • Cyclin E levels were elevated and there was increased association of cyclin E/Cdk2 with Mcl-1 in ABT-737-resistant compared to parental cells. (oncotarget.com)
  • Studies with Mcl-1 phosphorylation mutants show that cyclin E/Cdk2-dependent phosphorylation of Mcl-1 residues on its PEST domain resulted in increased Mcl-1 stability (Thr92, and Thr163) and Bim binding (Ser64). (oncotarget.com)
  • Cyclin A is involved in both S-phase and G2/M transitions of the cell cycle through its association with cdk2 and cdk1, respectively. (bdbiosciences.com)
  • Cyclin-dependent kinase 2 (Cdk2)/cyclin A is a novel PR coregulator that binds the NTD and acts by phosphorylating steroid receptor coactivator-1 and modulating steroid receptor coactivator-1 interaction with PR. (nih.gov)
  • however, phosphorylation of serine 400 was not required, indicating that JDP-2 and Cdk2/cyclin A act by distinct mechanisms. (nih.gov)
  • Violin plots show distribution of expression levels for Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SMED30002728) in cells (dots) of each of the 12 neoblast clusters. (stowers.org)
  • Expression of Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SMED30002728) in the t-SNE clustered sub-lethally irradiated X1 and X2 cells. (stowers.org)
  • Violin plots show distribution of expression levels for Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SMED30002728) in cells (dots) of each of the 10 clusters of sub-leathally irradiated X1 and X2 cells. (stowers.org)
  • Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. (wikipedia.org)
  • The human homolog of Cdk1, CDK1, shares approximately 63% amino-acid identity with its yeast homolog. (wikipedia.org)
  • Furthermore, human CDK1 is capable of rescuing fission yeast carrying a cdc2 mutation. (wikipedia.org)
  • Cdk1 also contains a PSTAIRE helix, which, upon cyclin binding, moves and rearranges the active site, facilitating Cdk1 kinase activities. (wikipedia.org)
  • When bound to its cyclin partners, Cdk1 phosphorylation leads to cell cycle progression. (wikipedia.org)
  • however, when phosphorylated by Cln3-Cdk1, Whi5 is ejected from the nucleus, allowing for transcription of the G1/S regulon, which includes the G1/S cyclins Cln1,2. (wikipedia.org)
  • G1/S cyclin-Cdk1 activity leads to preparation for S phase entry (e.g., duplication of centromeres or the spindle pole body), and a rise in the S cyclins (Clb5,6 in S. cerevisiae). (wikipedia.org)
  • Cdk1 phosphorylation also leads to the activation of the ubiquitin-protein ligase APCCdc20, an activation which allows for chromatid segregation and, furthermore, degradation of M-phase cyclins. (wikipedia.org)
  • Most obviously, Cdk1 is regulated by its binding with its cyclin partners. (wikipedia.org)
  • furthermore, cyclins impart specificity to Cdk1 activity. (wikipedia.org)
  • Furthermore, cyclins can target Cdk1 to particular subcellular locations. (wikipedia.org)
  • In addition to regulation by cyclins, Cdk1 is regulated by phosphorylation. (wikipedia.org)
  • Multisite phosphorylation, by Cdk1-Cln1/2, of Sic1 is thought to time Sic1 ubiquitination and destruction, and by extension, the timing of S-phase entry. (wikipedia.org)
  • controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. (proteopedia.org)
  • Other G 2 /M regulatory molecules such as Cdc25C, Cdk1, cyclin B1 were down-regulated by DIM. (aspetjournals.org)
  • Cdk5 is named after its structural similarity to members of the serine/threonine cyclin-dependent kinase family. (frontiersin.org)
  • Mutation of phosphorylation sites within this region of the NTD showed that phosphorylation of serine 400 was required for the partial agonist activity of RU486 stimulated by JDP-2, but was not required for activity of hormone agonist, either in the presence or absence of JDP-2. (nih.gov)
  • We conclude that PR bound to RU486 and associated with JDP-2 adopts an active conformation in a subregion of the NTD requiring phosphorylation of serine 400 that is distinct from that promoted by progestin agonists. (nih.gov)
  • Further, we show that the basal transcription factor TFIIH is constitutively recruited by ER-Y537S, resulting in ligand-independent phosphorylation of Serine 118 (Ser118) by the TFIIH kinase, cyclin-dependent kinase (CDK)7. (essex.ac.uk)
  • Anantin application caused preferential P2X3 receptor redistribution to the lipid raft compartment and decreased P2X3 serine phosphorylation, two phenomena that were not interdependent. (biomedcentral.com)
  • Tonic inhibition of P2X3 receptor activity by BNP/NPR-A/PKG pathways occurs via two distinct mechanisms: P2X3 serine phosphorylation and receptor redistribution to non-raft membrane compartments. (biomedcentral.com)
  • Inhibition of Cdk5 resulted in dephosphorylation of the inhibitory Ser9 site on GSK3β and an increase of activating phosphorylation at Tyr216. (frontiersin.org)
  • Furthermore, inhibition of ChoK shows a strong in vivo antitumor activity against human breast cancer xenografts. (aacrjournals.org)
  • E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. (ox.ac.uk)
  • The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. (ox.ac.uk)
  • Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. (ox.ac.uk)
  • Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. (ox.ac.uk)
  • Expression Predicts Therapeutic Response to Oxidative Phosphorylation Inhibition in Ovarian Cancer. (viictr.org)
  • These effects were associated with the inhibition of the phosphorylation of tubulin, as well as the induction of multiple pathways that lead to cell death. (sunquicksf.com)
  • To avoid elimination by this mechanism, human papillomaviruses (HPV) have developed several mechanisms that enable the cells they infect to elude both extrinsic and intrinsic apoptosis. (mdpi.com)
  • In this study, we found that hSulf-1 overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT) phosphorylation and limiting CDK4 nuclear import. (oncotarget.com)
  • Low PDCD4 level was associated with reduced proliferation but not apoptosis or phosphorylation of endothelial nitric oxide synthase caused by pulsatile shear stress to help maintain the homeostasis of endothelial cells. (plos.org)
  • At least some cyclins contain a hydrophobic patch which may directly interact with substrates, conferring target specificity. (wikipedia.org)
  • Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. (ox.ac.uk)
  • In S. pombe, for example, incomplete DNA synthesis may lead to stabilization of this phosphorylation, preventing mitotic progression. (wikipedia.org)
  • Cyclin-dependent kinase (CDK) 10, is reported to play an essential role in the progression from the G2 to M phase of the cell cycle. (jcancer.org)
  • These results demonstrate that ChoK plays an essential role in both normal human mammary epithelial cell proliferation and breast tumor progression. (aacrjournals.org)
  • Here, we ask whether the expression of HIV-1 genes in infected podocytes induces cyclin D 1 and phospho-pRb (Ser780) expression, hallmarks of cyclin D1-mediated G 1 → S phase progression. (biomedcentral.com)
  • Compared to controls, cultured podocytes expressing HIV-1 genes, and podocytes and tubular epithelium from hyperplastic nephrons in Tg26 kidneys, had increased levels of phospho-pRb (Ser780), a target of active cyclin D 1 /cyclin-dependent kinase-4/6 known to promote G 1 → S phase progression. (biomedcentral.com)
  • In comparison to the two general alternative mechanisms utilized by known transforming viruses to promote cell-cycle progression, namely, by activating or bypassing endogenous D-type cyclins (herein, referred to as "cyclin D"), it has not been established whether HIV-1 gene products trigger either cyclin D-dependent or cyclin D-independent proliferation in non-lymphoid tissues [ 15 ]. (biomedcentral.com)
  • Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. (ox.ac.uk)
  • During cell cycle progression the centrosome undergoes a series of major structural and functional transitions that are regulated in part by phosphorylation. (le.ac.uk)
  • Here we show that human shugoshin 2 (SGO2), an essential protector of meiotic cohesin with unknown functions in the soma 6 , 7 , is turned into a separase inhibitor upon association with SAC-activated MAD2. (nature.com)
  • Endogenous regulation of the cell cycle depends on phosphorylation and dephosphorylation of the cyclin- cyclin-dependent kinase (CDK)-cyclin-dependent kinase inhibitor (CDKI) pathway. (jcancer.org)
  • The selective suppression of HIV-1 transcription by the cyclin-dependent kinase inhibitor, flavopiridol, abrogated cyclin D 1 expression, underlying the requirement for HIV-1 encoded products to induce cyclin D 1 . (biomedcentral.com)
  • The CDK7 inhibitor, THZ1 prevented Ser118 phosphorylation and inhibited growth of MCF7-Y537S cells. (essex.ac.uk)
  • 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 p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • Collectively, our findings identify a novel mechanism of cyclin E-mediated Mcl-1 regulation that provides a rationale for clinical use of Bcl-2 family and Cdk inhibitors for Mcl-1-dependent tumors. (oncotarget.com)
  • De-regulation of cell-cycle control, in particular G 1 - to S-phase transition, is implicated in the pathogenesis of most types of human cancer, including ovarian cancer ( 1 ). (iiarjournals.org)
  • This work substantially advances our understanding of Nek2 regulation and brings us closer to understanding how centrosome cohesion is regulated through specific phosphorylation of components such as C-Nap1. (le.ac.uk)
  • Introduction: The human Pituitary Tumor Transforming Gene (hPTTG) is a phosphorylated proto-oncogene induced in multiple tumour types. (endocrine-abstracts.org)
  • This gene exhibits elevated expression levels in multiple human cancers. (cancerindex.org)
  • Recently, reduced expression of CDK10 has been observed in several cancerous human tissue, suggesting that CDK10 is a tumor suppressor gene. (jcancer.org)
  • EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. (proteopedia.org)
  • Indeed, HIV-1 virus deleted of nef failed to induce cyclin D 1 mRNA to the level of other single gene mutant viruses. (biomedcentral.com)
  • The human sulfatase 1 (hSulf-1) gene encodes an aryl sulfatase. (oncotarget.com)
  • Altered expression of this gene has been observed in multiple human cancers. (cancerindex.org)
  • Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. (ox.ac.uk)
  • We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. (ox.ac.uk)
  • This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
  • 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)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • We introduced BAC clones with human wild-type BRCA1 or variants into Brca1-null ES cells and confirmed that only wild-type and a known neutral variant rescued cell lethality. (jci.org)
  • In this issue of the JCI , Chang, Sharan, and colleagues describe a novel system to evaluate human BRCA1 alleles for in vivo function using BACs containing human BRCA1 vectors in mouse cells and embryos (see the related article beginning on page 3160). (jci.org)
  • Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
  • 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. (proteopedia.org)
  • Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. (proteopedia.org)
  • Cyclin E knock-down restored ABT-737 sensitivity to acquired and inherently resistant Mcl-1-dependent tumor cells. (oncotarget.com)
  • Here, we have investigated the role of ChoK in the development of breast cancer and found that ChoK is both necessary and sufficient for growth factor-induced proliferation in primary human mammary epithelial cells and an absolute requirement for the specific mitogenic response to heregulin in breast tumor-derived cells. (aacrjournals.org)
  • Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. (ox.ac.uk)
  • The objective of this study was to optimize conditions for preparing Boswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells. (biomedcentral.com)
  • Similar to our previous observations in human bladder cancer cells, Boswellia sacra essential oil induces breast cancer cell-specific cytotoxicity. (biomedcentral.com)
  • Human CCA cell lines (MzChA-1, HuCCT1), normal human cholangiocyte (H69), human hepatic stellate cells (LX-2), macrophages (RAW 264.7), and primary hepatic cells were used for cellular and molecular biology assays. (bvsalud.org)
  • Fenbendazole has also been shown to inhibit the growth of human melanoma, ovarian and prostate cancer cells in vitro. (sunquicksf.com)
  • Another exciting finding in the research of fenben for humans is that this compound can reactivate the p53 genome in cancer cells. (sunquicksf.com)
  • However, one antibody recognised both ABCB5fl and ABCB5β, and was subsequently used to evaluate protein expression levels in other cell types.siRNA knockdown of ABCB5 in human mammary epithelial cells (HMECs) caused a concomitant reduction in p16 expression and an increase in cellular proliferation. (qmul.ac.uk)
  • En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)
  • Application of unidirectional pulsatile shear stress to human umbilical vein endothelial cells (HUVECs) decreased PDCD4 protein but not mRNA level. (plos.org)
  • The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is frequently de-regulated in human cancer. (babraham.ac.uk)
  • We suggest that these tumours may arise through a mechanism involving ATP depletion, activation of AMPK, and induction of cyclin D1, and that this may be a unique pathway of tumour development that has the potential for therapeutic intervention in these rare tumours. (dundee.ac.uk)
  • The CDK4/Cyclin D complex is also negatively regulated by p21/CIP1/CDKN1A and p27/Kip1. (rndsystems.com)
  • Programmed cell death 4 (PDCD4) is an important tumor suppressor in the development of various human cancers [1] and inhibits translation rather than transcription. (plos.org)
  • Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
  • In addition, the potential for these genes to perform various cognitive roles during human brain evolutionary processes is discussed. (biomedcentral.com)
  • CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. (cancercentrum.se)
  • Phosphorylation of RB1 disturbs its interaction with E2F1. (proteopedia.org)
  • Cyclin E depletion in various human tumor cell-lines and cyclin E -/- mouse embryo fibroblasts showed decreased levels of Mcl-1 protein, with no change in Mcl-1 mRNA levels. (oncotarget.com)
  • Ovulatory surges of human CG prevent hormone-induced granulosa cell tumor formation leading to the identification of tumor-associated changes in the transcriptome. (cancercentrum.se)
  • HIV-1-infected podocytes showed markedly elevated cyclin D 1 mRNA and cyclin D 1 protein, the latter of which did not down-regulate during cell-cell contact or differentiation, suggesting post-transcriptional stabilization of cyclin D 1 protein levels by HIV-1. (biomedcentral.com)
  • Activation of CDK4 requires binding of a D-type Cyclin and phosphorylation of Thr172 by the CAK kinase complex. (rndsystems.com)
  • G 2 /M arrest was associated with DNA damage as indicated by phosphorylation of H 2 A.X at Ser139 and activation of checkpoint kinase 2 (Chk2) in all the three cell lines. (aspetjournals.org)
  • 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)
  • ATCC CCL-243) were probed with the mouse anti-human cyclin A antibody at concentration of 2.0 µg/mL (lane 1), 1.0 µg/mL (lane 2), and 0.5 µg/mL (lane 3). (bdbiosciences.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Nischarin (NISCH) in samples from Tissue homogenates and other biological fluids. (lotuskringpoeldijk.nl)
  • 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)
  • We further confirmed that hSulf-1 overexpression can inhibit AKT phosphorylation and CDK4 nuclear localization and retard the growth of melanoma xenograft tumors in nude mice. (oncotarget.com)
  • HIV-1 expression induces cyclin D 1 and phospho-pRb (Ser780) expression in infected podocytes, suggesting that HIV-1 activates cyclin D1-dependent cell-cycle mechanisms to promote proliferation of infected renal epithelium. (biomedcentral.com)
  • This destruction follows ubiquitylation by the APC/C-Cdc20 complex and depends on a novel destruction motif which is highly related to the extended D box present in cyclin A. Previous work has indicated that Nek2 may regulate centrosome cohesion through phosphorylation of the core centrosomal protein C-Nap1. (le.ac.uk)
  • Cyclin A may also form a complex with the adenovirus oncoprotein E1A which has DNA binding activity. (bdbiosciences.com)
  • Moreover, a C-terminally adjacent autoinhibitory domain (AID) (935-1050) was identified in HIPK2, based on the observation that its removal increases phosphorylation activity 13 . (nature.com)
  • Human sulfatase 1 (hSulf-1) has aryl sulfatase activity. (oncotarget.com)
  • Faha B, Ewen ME, Tsai LH, Livingston DM, Harlow E. Interaction between human cyclin A and adenovirus E1A-associated p107 protein. (bdbiosciences.com)
  • In the absence of cyclin E, Mcl-1 ubiquitination was enhanced, leading to decreased protein stability. (oncotarget.com)