Inhibits phosphorylation of cyclin. Medical search. Frequent questions

In addition to this catalytic core, Cdk1, like other cyclin-dependent kinases, contains a T-loop, which, in the absence of an interacting cyclin, prevents substrate binding to the Cdk1 active site. (wikipedia.org)
We describe here the meriolins, a new family of inhibitors of cyclin-dependent kinases (CDK). (rcsb.org)
Malumbres, M. Cyclin-dependent kinases. (nature.com)
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). (rcsb.org)
We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). (rcsb.org)
A relatively well understood example is the network that controls progression of the cell cycle, where cyclin-dependent kinases (CDKs) couple with various cyclins over the cell cycle to regulate critical processes [ 2 - 4 ]. (biomedcentral.com)
Cyclin-dependent kinases (Cdks) are principal drivers of cell division and are an important therapeutic target to inhibit aberrant proliferation. (escholarship.org)
We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases. (mdanderson.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)
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)
Phosphorylation at CDK1, CDK4, and CDK9 sites on, respectively, protein phosphatase 1alpha, retinoblastoma protein, and RNA polymerase II is inhibited in neuroblastoma SH-SY5Y cells exposed to meriolins. (rcsb.org)
JIB extract induced cell cycle arrest at the G 0 /G 1 phase and decreased cyclin and cdk protein expressions. (medsci.org)
Antiproliferative and apoptotic effects of silymarin and silibinin were associated with decreases in (a) cyclin D1 protein level and extracellular signal-regulated kinase-1/2 phosphorylation and in (b) protein levels of survivin and nuclear phospho-p65 (Ser(276) and Ser(536)), respectively. (nih.gov)
The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. (nih.gov)
The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
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)
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)
phosphorylation of Rb protein on Ser780 and Ser811 is inhibited by miR-503. (biomedcentral.com)
The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. (cancerindex.org)
B ) Western blot analysis of HSP90 (loading control) CDK1, cyclin A2, CDK2, cyclin E2 protein levels in macrophages treated with carrier (DMSO), AhR agonist or antagonist. (elifesciences.org)
The level of protein phosphorylation at specific sites varies from less than 1% to greater than 90%, depending on conditions [ 26 ]. (biomedcentral.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)
Cdk enzymatic activity is tightly controlled through cyclin interactions, posttranslational modifications, and binding of inhibitors such as the p27 tumor suppressor protein. (escholarship.org)
Here DARPP-32 phosphorylation by protein kinase A (PKA), DARPP-32 into a powerful protein phosphatase 1 (PP1) inhibitor. (pp1a.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 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)
In the absence of cyclin E, Mcl-1 ubiquitination was enhanced, leading to decreased protein stability. (oncotarget.com)
This protein kinase is composed of a catalytic subunit (Cdc2), a regulatory subunit (cyclin B) and a low molecular weight subunit (p13-Suc1). (neobiotechnologies.com)
Evidence has established that B type cyclins not only act on M phase regulatory subunits of the Cdc2 protein kinase, but also activate the Cdc25A and Cdc25B endogenous tyrosine phosphatase, of which Cdc2 is the physiological substrate. (neobiotechnologies.com)
The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
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)

Interestingly, inhibition of FAK signaling pathway attenuated the phosphorylation of AKT, but inhibition of AKT signaling pathway did not affect the phosphorylation of FAK. (oncotarget.com)
The inhibition of Torc1 by rapamycin mimics nutrient starvation and causes an array of physiological changes that include global changes in gene expression, phosphorylation/dephosphorylation of various factors, decreased cell growth, degradation of proteins, and ultimately cell cycle arrest in the G 1 phase [4, 9-11]. (researchsquare.com)
Figure3A) 3 suggesting that inhibition mTOR2 in PDAC may be a viable approach to inhibit cell growth. (globaltechbiz.com)
Using fluorescein isothiocyanate (FITC)-conjugated LAB to track its cellular localization, we show that LAB localizes to the nucleus, specifically to the nucleolus, where it binds to histone H3, leading to the inhibition of the platelet-derived growth factor (PDGF)-induced phosphorylation of histone H3. (elsevierpure.com)

Tyrosine phosphorylation inhibits the Cdc2/ cyclin B enzyme, and tyrosine dephosphorylation, occurring at the onset of mitosis, directly activates the pre-MPF complex. (neobiotechnologies.com)

The N-terminal phosphorylation of RB by p38 bypasses its inactivation by CDKs and prevents proliferation in cancer cells. (nature.com)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)

A ) Quantitative PCR analysis of CDK1, cyclin A2, CDK2, cyclin E2 and CYP1B1 mRNA levels in macrophages treated with carrier (DMSO), AhR agonist or AhR antagonist. (elifesciences.org)
We find that Spy1 confers structural changes to Cdk2 that obviate the requirement of Cdk activation loop phosphorylation. (escholarship.org)
Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (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)

p16 inhibits cyclin-dependent kinase, which results in retinoblastoma phosphorylation and blockage of cell cycle at G1 phase. (iium.edu.my)

Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
The structures of pCDK2/cyclin A/variolin B and pCDK2/cyclin A/meriolin 3 complexes reveal that the two inhibitors bind within the ATP binding site of the kinase, but in different orientations. (rcsb.org)
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)
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)
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)

At least some cyclins contain a hydrophobic patch which may directly interact with substrates, conferring target specificity. (wikipedia.org)
Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. (nih.gov)
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)

phosphorylation of these proteins leads to cell cycle progression. (wikipedia.org)
Cdk1-cyclin complexes are also governed by direct binding of Cdk inhibitor proteins (CKIs). (wikipedia.org)
These findings suggest that parasite proteins are able to inhibit erythroid cell growth by down-regulation of ezrin phosphorylation, leading to ineffective erythropoiesis ultimately resulting in severe malarial anaemia. (biomedcentral.com)
Many molecular pathways in eukaryotic cells are modulated by specific signaling proteins that are controlled, by phosphorylation and dephosphorylation, through the activity of kinase and phosphatase enzymes. (biomedcentral.com)
We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
instead of attempting to predict individual phosphorylation sites, we search for proteins that contain high densities of strong and weak consensus matches that are closely spaced in the primary amino acid sequence. (biomedcentral.com)

MDM2 binds to and inhibits TP53 activity. (medscape.com)

These potent effects are driven by curcumin's ability to induce G2/M cell cycle arrest, induce autophagy, activate apoptosis, disrupt molecular signaling, inhibit invasion and metastasis, and increase the efficacy of current chemotherapeutics. (hindawi.com)
Together, these results suggest that silymarin and silibinin inhibit chemically induced urinary bladder tumor growth and progression possibly by inhibiting cell proliferation and enhancing apoptosis. (nih.gov)
Indeed apoptosis is inhibited in senescent cells. (globale-dermatologie.com)

Roscovitine is a cyclin-dependent kinase (cdk) inhibitor. (tocris.com)
This gene encodes a potent cyclin-dependent kinase inhibitor. (nih.gov)
Incorporation of both FAK inhibitor and AKT inhibitor counteracted the upregulating expression of Cyclin A2, CyclinB1, and Snail, and downregulating expression of E-cadherin expression induced by Lasp1 overexpression. (oncotarget.com)

Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. (nih.gov)
At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. (nih.gov)
Conversely Rictor siRNA and mTOR siRNA both inhibited Akt (S)-Tedizolid phosphorylation and downregulated Cyclin D1 and CDK4 expression. (globaltechbiz.com)

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)
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)

The Cdc/cyclin enzyme is subject to multiple levels of control, of which the regulation of the catalytic subunit by tyrosine phosphorylation is the best understood. (neobiotechnologies.com)

In addition, AKT/mTOR signaling and MAPK signaling were inhibited by JIB extract to suppress melanoma cell growth and proliferation. (medsci.org)
In conclusion, Lasp1 facilitated tumor proliferation and invasion of NSCLC through directly binding to FAK and enhancing the phosphorylation of FAK (Tyr397) and AKT (Ser473). (oncotarget.com)
In previously reports , Plasmodium vivax was found to be able to directly inhibited erythroid cell proliferation and differentiation. (biomedcentral.com)
Moreover, in vitro cultures of erythroid cells derived from haematopoietic stem cells has demonstrated that P. vivax is able to directly inhibit erythroid cell proliferation and differentiation [ 22 ]. (biomedcentral.com)
Lithospermic acid B (LAB), an active component of danshen, is known to inhibit the proliferation of vascular smooth muscle cells (VSMCs) and has pharmacological activity scavenging free radicals in VSMCs. (elsevierpure.com)
Knockdown of NMHC-IIA expression impeded the function of LAB, which was then unable to inhibit the PDGF-induced proliferation of VSMCs. (elsevierpure.com)

Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex, also called positive transcription elongation factor B (P-TEFB), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNAP II) (PubMed:9499409, PubMed:15563843). (wuxibiortus.com)
DRB inhibits phosphorylation of the carboxy-terminal domain (CTD) of the polymerase large subunit by blocking the P-TEFb (Cdk9-cyclin T) kinase. (whatisflike.com)

Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). (nih.gov)
Alpha amanitin inhibits RNA polymerase II (pol II) by blocking initiation and elongation of transcription. (whatisflike.com)
How does Alpha Amanitin inhibit RNA polymerase? (whatisflike.com)
Which RNA polymerase in man is inhibited by Amanitin? (whatisflike.com)

In yeast, rapamycin inhibits the TORC1 kinase signaling pathway causing rapid alteration in gene expression and ultimately cell cycle arrest in G 1 through mechanisms that are not fully understood. (researchsquare.com)

Meriolin 3 potently inhibits tumor growth in two mouse xenograft cancer models, namely, Ewing's sarcoma and LS174T colorectal carcinoma. (rcsb.org)

In S. pombe, for example, incomplete DNA synthesis may lead to stabilization of this phosphorylation, preventing mitotic progression. (wikipedia.org)

GSK-3 has been shown to regulate cyclin D1 proteolysis and subcellular localization (5). (cellsignal.com)

p16 Ink4a downregulation leads to an activation of PKA-CREB-PGC1α signaling through increased phosphorylation of PKA regulatory subunits. (diabetesjournals.org)

Concurrent deletion of cyclin E1 and cyclin-dependent kinase 2 in hepatocytes inhibits DNA replication and liver regeneration in mice. (nature.com)
AhR activation inhibits HIV-1 replication in macrophages. (elifesciences.org)
the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed:20493174). (wuxibiortus.com)

integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed:15564463, PubMed:19575011, PubMed:19844166). (wuxibiortus.com)
Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245). (wuxibiortus.com)

α-Amanitin-Inhibiting RNA Polymerases II and III Amanitin binds with high specificity and high affinity (Ki = 3-4 nM) near the catalytic active site of RNAP II. (whatisflike.com)

The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351). (wuxibiortus.com)

RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). (wuxibiortus.com)
AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. (wuxibiortus.com)
DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:9857195, PubMed:10912001, PubMed:11112772). (wuxibiortus.com)
Baclofen inhibits the glycogen synthase kinase 3/β-catenin and signal transducer and activator of transcription 3 pathways. (bioz.com)
A and B: Phosphorylation of glycogen synthase kinase 3 (GSK3) and signal transducer and activators of transcription 3 is decreased after baclofen treatment in both cholangiocarcinoma cell lines, both cultured in normal glucose and high glucose conditions. (bioz.com)
How does mushroom toxin alpha Amanitin inhibits the process of transcription? (whatisflike.com)
How does DRB inhibit transcription? (whatisflike.com)

CDK9/Cyclin T2-H00A-Wuxi Biortus Biosciences Co. Ltd. (wuxibiortus.com)

Therefore, co-targeting the aberrant cyclin and FGFR pathways resulted in long-term exceptional response in a patient with refractory advanced osteosarcoma. (biomedcentral.com)

Edu incorporation showed that OSI-027 also significantly inhibited DNA synthesis. (globaltechbiz.com)

CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. (cancercentrum.se)

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)

miR-503 inhibited significantly the expression of CDK6 and the downstream genes of E2F3. (biomedcentral.com)
Lysed IE significantly inhibited gEC growth at 48 and 72 h and cell division resulting in the accumulation of cells in G0 phase. (biomedcentral.com)

DARPP-32 can itself inhibit the following PKA DARPP-32 phosphorylation by cyclin-dependent kinase 5 (Cdk5). (pp1a.com)

Acetylation of H4-K16 neutralizes its basic charge and inhibits compaction of the chromatin. (biomedcentral.com)

this phosphorylation is thought to alter ATP orientation, preventing efficient kinase activity. (wikipedia.org)
Fig. 4: Pirfenidone inhibits p38γ activity and protects against DEN-induced HCC. (nature.com)
GSK-3 is a critical downstream element of the PI3K/Akt cell survival pathway whose activity can be inhibited by Akt-mediated phosphorylation at Ser21 of GSK-3α and Ser9 of GSK-3β (2,3). (cellsignal.com)
The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). (wuxibiortus.com)

However, MEKi pre-treatment, which blocks ERK2 pT-E-pY phosphorylation and dissociation from MEK1/2, prevents ERK2 turnover. (babraham.ac.uk)

Rapamycin-induced G 1 arrest does not involve detectable phosphorylation of the MAPKs, Kss1 and Fus3, as reported for α factor-induced G 1 arrest. (researchsquare.com)

Subsequent western blot results revealed that Lasp1 promoted the expression of Cyclin A2, CyclinB1, and Snail, and inhibited the expression of E-cadherin. (oncotarget.com)
Notably, LAB suppressed the PDGF-induced phosphorylation of Akt and the expression of cyclin D2 in the presence of NMHC-IIA expression. (elsevierpure.com)

The physiological relevance of E2F1 in the DNA damage response is now being explored using a novel knock-in mouse model we developed that blocks E2F1 phosphorylation by ATM/ATR. (mdanderson.org)

The two B type cyclins, cyclin B1 and cyclin B2, have been shown to have distinct tissue distributions. (neobiotechnologies.com)

however, they are inhibited by Sic1, preventing premature S phase initiation. (wikipedia.org)

Anatomy18

Organisms10

Diseases1

Chemicals and Drugs158

Analytical, Diagnostic and Therapeutic Techniques and Equipment16

Phenomena and Processes49

Disciplines and Occupations1

Information Science3

Kinases8

Protein23

Inhibition4

Cdc21

CDKs2

Cdk25

Retinoblastoma1

Inhibitors5

Substrates3

Proteins6

Binds to and inhibits1

Apoptosis3

Inhibitor3

CDK43

Cdk19

Catalytic subunit1

Proliferation6

Subunit2

Polymerase4

Signaling pathway1

Tumor growth1

Progression1

Regulate1

Regulatory subunits1

Replication3

Histone2

Specificity1

Kinase activity towards1

Transcription7

CDK91

Aberrant1

Synthesis1

Methylation1

Phosphorylate1

Significantly2

Cdk51

Chromatin1

Activity4

ERK21

Arrest1

Expression2

Physiological1

Distinct1

Phase1