• Cyclins function as regulators of CDKs (cyclin-dependent kinase). (wikipedia.org)
  • The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
  • Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. (rcsb.org)
  • The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. (rcsb.org)
  • Cell division is thought to be initiated by cyclin-dependent kinases (Cdks) inactivating key transcriptional inhibitors. (bvsalud.org)
  • CDKs are cyclin-dependent serine-/threonine-specific proteins kinases, the experience of which depends upon cyclin binding. (niepokorny.org)
  • Furthermore to people indirect results on cell routine legislation, the viral proteins kinase pUL97 straight cross-talks with CDKs since it mimics CDKs in phosphorylating partly-identical substrates and evidently possesses commonalities in protein framework and functionality. (niepokorny.org)
  • Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. (nature.com)
  • The protein encoded by this gene is a member of the CMGC family of serine/threonine protein kinases. (cancerindex.org)
  • Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases. (umbc.edu)
  • Serine/Threonine Kinases (STKs), Cyclin-dependent protein kinase 4 (CDK4) and CDK6-like subfamily, catalytic (c) domain. (umbc.edu)
  • HIPKs belong to the CMGC group of serine/threonine kinases and are part of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. (nature.com)
  • C-terminally adjacent to the HID follows a proline, glutamate, serine, and threonine (PEST)-rich domain, mediating proteasomal degradation of these kinases. (nature.com)
  • During G1, cyclin D-dependent kinase-mediated phosphorylation of Rb at Ser-795 marks the conversion of Rb from a transcriptionally repressive, hypophosphorylated state to an inactive, phosphorylated state, which may be sustained through mitosis by differential phosphorylation of up to 16 putative serine or threonine residues. (affbiotech.com)
  • Cyclin D1-CDK4 also enables the activation of cyclin E-CDK2 complex by sequestering Cip/Kip family CDK inhibitory proteins p21 and p27, allowing entry into the S phase. (wikipedia.org)
  • miR-34a inhibits CDK2 CDK4 and CDK6 as well as E2F a transcription factor that after release from the retinoblastoma tumor suppressor Rb initiates S-phase entry. (careersfromscience.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)
  • v-Jun overrides the mitogen dependence of S-phase entry by deregulating retinoblastoma protein phosphorylation and E2F-pocket protein interactions as a consequence of enhanced cyclin E-cdk2 catalytic activity. (ox.ac.uk)
  • We show that v-Jun enables cells to express cyclin A and cyclin A-cdk2 kinase activity in the absence of growth factors and that deregulation of cdk2 is required for S-phase entry. (ox.ac.uk)
  • This is the first report, however, that cyclin E-cdk2, rather than D-cyclin-cdk, is likely to be the critical Rb kinase target of v-Jun. (ox.ac.uk)
  • In HCMV-infected cells, particular subsets of CDK-cyclin complexes are downregulated/suppressed (CDK4-cyclin D, CDK6-cyclin D, CDK2-cyclin A) or upregulated/turned on (CDK1-cyclin B, CDK2-cyclin E), leading to an early on S stage arrest termed pseudomitosis [11] eventually. (niepokorny.org)
  • Predicated on series evaluation and a 3D style of pUL97, the viral kinase displays structural similarity to CDK2 in the catalytic middle and in functionally essential residues from the ATP binding site [16]. (niepokorny.org)
  • Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors. (rcsb.org)
  • Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases. (proteopedia.org)
  • CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. (umbc.edu)
  • Cyclin-dependent kinase (cdk) inhibitors have the potential to induce growth arrest and apoptosis in cancer cells. (omecamtivmecarbilactivator.com)
  • Current scientific trials are looking into cyclin-dependent kinase (CDK) inhibitors, such as for example roscovitine, an inhibitor of CDK1, -2, -5, -7, and -9, that lowers viral DNA synthesis, creation of late protein and infectious pathogen particles [4]. (niepokorny.org)
  • 8-13 Tyrosine kinase inhibitors (TKI) (imatinib, sunitinib, and regorafenib) have dramatically changed the treatment landscape and outcomes for gastrointestinal stromal tumour (GIST), one of the most common STS subtypes. (emjreviews.com)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (wikipedia.org)
  • Cyclin D1 is a regulatory subunit of cyclin-dependent kinases CDK4 and CDK6. (wikipedia.org)
  • This kinase is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression and G1/S transition. (cancerindex.org)
  • Although DBF4-dependent kinase (DDK) complex composed of CDC7 kinase and its regulatory subunit DBF4 has been shown to be overexpressed in primary tumors and promotes tumor development, while its role and prognostic value in HCC remain largely unknown. (biomedcentral.com)
  • The DBF4-dependent kinase (DDK) composed of CDC7 kinase and its regulatory subunit DBF4, which is required for CDC7 kinase activity, is a critical regulator of DNA replication by catalyzing MCM helicase (MCM2-7) (Fig. 1 A) [ 6 , 7 ]. (biomedcentral.com)
  • Surprisingly, purified and endogenous phosp27-CDK4-CycD1 complexes were insensitive to the CDK4-targeting drug palbociclib. (rcsb.org)
  • The cyclinD/CDK4/6 complexes induce the phosphorylation of retinoblastoma (Rb) protein and the release of E2F, which trigger G1 cell cycle progression. (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)
  • We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
  • The CDK4/6-like 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. (umbc.edu)
  • Homeodomain-interacting protein kinases (HIPKs) belong to the CMGC kinase family and are closely related to dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs). (nature.com)
  • For the class II DYRK ortholog from D. melanogaster it was demonstrated that the critical tyrosine is cis -auto-phosphorylated by the nascent kinase in a transitory intermediate state during maturation at the ribosome 3 . (nature.com)
  • 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)
  • 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)
  • This kinase, as well as CDK4, has been shown to phosphorylate, and thus regulate the activity of, tumor suppressor protein Rb. (cancerindex.org)
  • ADOS Proteins kinases are putative goals of brand-new herpesviral drugs because of their important function in the legislation of HCMV replication [3,4,5,6,7,8]. (niepokorny.org)
  • Its kinase area contains subdomains (SD) I-XI, that are conserved (aa 337C651) within herpesviral and mobile proteins kinases. (niepokorny.org)
  • Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. (neobiotechnologies.com)
  • The protein interaction landscape of the human CMGC kinase group. (nature.com)
  • In late-G1, Whi5 is rapidly hyper-phosphorylated by Cln1,2 in complex with the cyclin-dependent kinase Cdk1. (bvsalud.org)
  • Cln3-Cdk1 binds SBF-regulated promoters and Cln3's function can be performed by the canonical S5 kinase Ccl1-Kin28 when synthetically recruited to SBF. (bvsalud.org)
  • Based on a database search, we identified abemaciclib, an FDA-approved Cdk4/Cdk6 inhibitor used for the treatment of metastatic breast cancer, as potent inhibitor of HIPK2, HIPK3, and DYRK1A. (nature.com)
  • Findings In this phase 2 randomized clinical trial of 91 patients with endocrine-resistant, metastatic breast cancer who were previously treated with a cyclin-dependent kinase 4/6 inhibitor, participants were randomized to receive treatment with alisertib alone or combined with fulvestrant. (kanker-actueel.nl)
  • Meaning The trial results found that while alisertib did not restore fulvestrant sensitivity and increase ORRs, promising clinical activity was observed with alisertib monotherapy among patients with endocrine-resistant and cyclin-dependent kinase 4/6 inhibitor-resistant metastatic breast cancer. (kanker-actueel.nl)
  • In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. (nature.com)
  • In conclusion, these findings reveal cellular substrates and pathways regulated by the understudied Numb-associated kinase enzyme BIKE, a mechanism for CLINT1 regulation, and control of DENV infection via BIKE signaling, with potential implications for cell biology, virology, and host-targeted antiviral design. (bvsalud.org)
  • Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 μM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. (rcsb.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)
  • The expression and translocation of cyclinD1-CDK4 in post-mitotic neurons indicate that they may have supplementary functions in differentiated neurons that might be associated with neuronal plasticity. (biomedcentral.com)
  • In this study, we initiated to investigate the potential functions of cyclinD1-CDK4 in neuronal plasticity during the postnatal development in mice hippocampus area CA1. (biomedcentral.com)
  • These data claim that cyclin D-associated RTA 402 kinases and their pRB substrate will be the central players from the G1 checkpoint control. (bibf1120.com)
  • 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 protein dimerizes with CDK4/6 to regulate the G1/S phase transition and entry into the S-phase. (wikipedia.org)
  • Importance Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. (kanker-actueel.nl)
  • They are the first kinase activated by mitogenic signals to release cells from the G0 arrested state. (umbc.edu)
  • Remarkably, DYRK1A is inhibited by abemaciclib to the same extent as Cdk4/Cdk6 in vitro, raising the question of whether targeting of DYRK1A contributes to the transcriptional inhibition and therapeutic activity of abemaciclib. (nature.com)
  • Notably, the next SD includes an invariant lysine residue (K355), the substitute mutation which resulted in an entire lack of kinase activity [16,30,31]. (niepokorny.org)
  • It is a specific inhibitor of cdk4/cdk6, and a tumor suppressor involved in the pathogenesis of a variety of malignancies. (neobiotechnologies.com)
  • 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)
  • The signaling pathways and cellular functions regulated by the four Numb-associated kinases are largely unknown. (bvsalud.org)
  • Low expression of CDK6 protein in ZR-75-1, Neuro-2a, and INS-1 cells is consistent with the predicted expression pattern. (cellsignal.com)
  • Palbociclib instead primarily targeted monomeric CDK4 and CDK6 (CDK4/6) in breast tumor cells. (rcsb.org)
  • In contrast, in AR-transformed PC3 cells (PC3-AR), depletion of MYST1 induces cyclin-dependent kinase (CDK) N1A/p21, which results in G2M arrest. (mssm.edu)