• WAF1
  • Other than Rb, viral cyclin D-Cdk6 complex also targets p27Kip, a Cdk inhibitor of cyclin E and A. In addition, viral cyclin D-Cdk6 is resistant to Cdk inhibitors, such as p21CIP1/WAF1 and p16INK4a which in human cells inhibits Cdk4 by preventing it from forming an active complex with cyclin D. Growth factors stimulate the Ras/Raf/ERK that induce cyclin D production. (wikipedia.org)
  • The CIP/KIP family is made up of three proteins: p21cip1/waf1, P27kip1, p57kip2 These proteins share sequence homology at the N-terminal domain which allows them to bind to both the cyclin and CDK. (wikipedia.org)
  • binds
  • Rapamycin binds intracellularly to FK506 (tacrolimus)-binding proteins (FKBPs). (aspetjournals.org)
  • Viral cyclin D binds human Cdk6 and inhibits Rb by phosphorylating it, resulting in free transcription factors which result in protein transcription that promotes passage through G1 phase of the cell cycle. (wikipedia.org)
  • In its un-phosphorylated form, Rb binds a member of E2F family of transcription factors which controls expression of several genes involved in cell cycle progression (example, cyclin E). Rb acts as a repressor, so in complex with E2F it prevents expression of E2F-regulated genes, and this inhibits cells from progressing through G1. (wikipedia.org)
  • The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. (wikipedia.org)
  • It binds to CDK4/6 inhibiting its kinase activity and prevents Rb phosphorylation. (wikipedia.org)
  • By definition, a CDK binds a regulatory protein called a cyclin. (wikipedia.org)
  • inhibition
  • The inhibition of these kinases in biochemical reactions in vitro does not necessarily indicate that these kinases are targets of SU6656 in cells. (wikipedia.org)
  • Namely, cyclin D-Cdk4/6 complex partially phosphorylates retinoblastoma tumor suppressor protein (Rb), whose inhibition can induce expression of some genes (for example: cyclin E) important for S phase progression. (wikipedia.org)
  • complexes
  • The protein can be found in the cytoplasm and the nucleus, however most of the active complexes are found in the nucleus of proliferating cells. (wikipedia.org)
  • Importantly, these C-CDK complexes act as a kinase, phosphorylating and inactivating the protein of Rb and p-Rb related "pocket proteins" p107 and p130. (wikipedia.org)
  • CIP/KIP family proteins bind a wide range of G1/S and S-phase cyclin-CDK complexes including cyclin D-CDK4,6 and cyclin E-, A-CDK2 complexes. (wikipedia.org)
  • Futhurmore, mouse embryonic fibroblasts deficient for p21 and p27 had lower levels of cyclin D1 and immunoprecipitated cyclinD-CDK complexes had no kinase activity. (wikipedia.org)
  • This finding suggests that the ability of cyclinD-CDK complexes to sequester CIP/KIP proteins is predominates their inhibitory activity of CDK2. (wikipedia.org)
  • downstream
  • Three members of the Tec family, Itk, Rlk and Tec, are activated downstream of antigen receptor engagement in T cells and transmit signals to downstream effectors, including PLC-y. (allindianpatents.com)
  • The MAP kinase ERK activates the downstream transcription factors Myc, AP-1 and Fos which in turn activate the transcription of the Cdk4, Cdk6 and cyclin D genes, and increase ribosome biogenesis. (wikipedia.org)
  • This mechanism blocks any kinase activity and prevents downstream hyper-phosphorylation of Rb that allows release of the E2F transcription factor and transcription of cell cycle-related genes. (wikipedia.org)
  • CDK4
  • However, in recent years, new evidence proved that the presence of CDK6 is not essential for proliferation in every cell type, the cell cycle has a complex circuitry of regulation and the role of CDK6 might be more important in certain cell types than in others, where CDK4 or CDK2 can act as protein kinases compensating its role. (wikipedia.org)
  • One of the best known substrates of cyclin D/Cdk4 and -6 is the retinoblastoma tumor suppressor protein (Rb). (wikipedia.org)
  • p16 inhibits cyclin dependent kinases 4 and 6 (CDK4 and CDK6) and thereby activates the retinoblastoma (Rb) family of proteins, which block traversal from G1 to S-phase. (wikipedia.org)
  • however it was later discovered that CIP/KIP proteins, while inhibiting CDK2 activity, may also activate cyclin D-CDK4,6 activity by facilitating stable binding between cyclin D and CDK4,6. (wikipedia.org)
  • Therefore, it was hypothesized that additional proteins were needed to allow for a stable cyclin D-CDK4,6 complex. (wikipedia.org)
  • This model is supported by the finding that expression of either wild-type or catalytically inactive CDK4 can sequester CIP/KIP proteins resulting in cyclin E-CDK2 activation. (wikipedia.org)
  • potent
  • In an effort to identify additional CaMK inhibitors that exhibit more potent activity in triggering leukemia cell differentiation, we synthesized 45 analogues of KN-62 and determined their ability to induce HL-60 cell differentiation. (washington.edu)
  • differentiation
  • An extracellular stimulus may affect one or more cellular responses related to cell growth, migration, differentiation, secretion of hormones, activation of transcription factors, muscle contraction, glucose metabolism, control of protein synthesis, and regulation of the cell cycle. (allindianpatents.com)
  • SIRT2 appears to be the relevant target for cambinol-induced Daudi cell toxicity.KN-62, an inhibitor of the calmodulin-dependent protein kinases (CaMKs), enhances the terminal differentiation of retinoic acid sensitive human myeloid leukemia cell lines. (washington.edu)
  • For example, CDK6 is involved in the differentiation of T cells, acting as an inhibitor of differentiation. (wikipedia.org)
  • mutants
  • Recently, ponatinib was shown to be active against AC220-resistant kinase domain mutants of AML-expressing FLT3-ITD ( 6 , 11 ). (aacrjournals.org)
  • activates
  • P16/Rb pathway collaborates with the mitogenic signaling cascade for the induction of reactive oxygen species, which activates the protein kinase C delta, leading to an irreversible cell cycle arrest. (wikipedia.org)
  • biochemical
  • The farnesyltransferase inhibitors were developed from biochemical experiments on H-Ras proteins, and it is likely that K-Ras (and perhaps also N-Ras) proteins can be alternatively modified by geranylgeranylation when farnesyltransferase activity is blocked ( Adjei, 2001 ). (aspetjournals.org)
  • human
  • Here, we examined the effect of SFK inhibitors in NCI-H2052, ACC-MESO-4 and NCI-H28 cells, mesothelioma cell lines and Met5A, a human non-malignant mesothelial cell line. (oup.com)
  • We have previously identified the compound cambinol, an inhibitor of the human sirtuins SIRT1 and SIRT2, which is selectively toxic to Burkitt's lymphoma cells. (washington.edu)
  • mRNA
  • In eukaryotes, overexpression of translation initiation factor 4E (eIF4E) leads to an increased level of cyclin D protein and increased amount of cyclin D mRNA outside of the nucleus. (wikipedia.org)