Regulation cyclin dependent kinase inhibitor cyclin dependent kinase inhibitor. Medical search. Frequent questions

Our results suggest that BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway, which will provide an innovative experimental framework to study control of breast cancer cell proliferation. (nih.gov)
The mechanism of OGF-OGFr action on DNA synthesis was related to the cyclin-dependent kinase inhibitory pathway because knockdown of p16 or p21 in OVCAR-3 cells, and p21 in SKOV-3 cells, eliminated OGF's inhibitory effect on growth. (nih.gov)
A central step in the regulation of the activation of the FA-BRCA pathway is the mono-ubiquitination of the FANCD2 (and FANCI) proteins. (uri.edu)
Regulation of the activation of the Fanconi anemia pathway by the p21 cyclin-dependent kinase inhibitor. (uri.edu)
The Fanconi anemia pathway is required for the DNA replication stress response and the regulation of common fragile site stability. (uri.edu)
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)
However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
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)
This animation provides an overview of the androgen receptor (AR) signaling pathway and its interaction with cell cycle regulation. (lillymedical.com)
This slide deck examines the unmet need in advanced prostate cancer, the AR pathway, its interaction with cell cycle regulation, and novel approaches to enhance AR-targeting. (lillymedical.com)
The cyclin-dependent kinases pathway as a target for prostate cancer treatment: Rationale and future perspectives. (lillymedical.com)
DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)

Cyclin-dependent kinase inhibitor proteins are essential in the regulation of the cell cycle. (wikipedia.org)
Cyclin-dependent kinase inhibitor proteins work by inactivating the CDKs by degradation. (wikipedia.org)
Cyclin-dependent kinase inhibitor proteins use ATP as a phosphate contributor to phosphorylate serine and threonine residues. (wikipedia.org)
Seven cyclin-dependent kinase inhibitor proteins have been identified. (wikipedia.org)
The discovery of Cyclin-dependent kinase inhibitor proteins in 1990 opened the door in how we think about cell cycle control. (wikipedia.org)
The active cyclin/CDK complex then phosphorylates proteins, activates them, and sends the cell into the next phase of the cell cycle. (wikipedia.org)
see RTKRas/MAP kinase signaling ), LIN-12 (see LIN-12/Notch signaling in C. elegans ), and WNT (see Wnt signaling ), as well as the functions of the SynMuv and mediator proteins (see Transcriptional regulation ). (wormbook.org)
Regulation can occur through modification of the p27 protein's structure, its interaction with other proteins, or its localization within the cell. (medlineplus.gov)

A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin-dependent kinase (CDK) and Cyclin activity by stopping the cell cycle if there are unfavorable conditions, therefore, acting as tumor suppressors. (wikipedia.org)
PTEN encodes a protein kinase of the same name and functions as a tumor suppressor through regulation of cell proliferation. (medscape.com)
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)
BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy. (biomedcentral.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)

Additionally, the mRNA and protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (pRb), was further down-regulated under exposure to lovastatin in condition of BRCA1 overexpression, but the expression of p21WAF1/CIP1, a cyclin-dependent kinase inhibitor (CDKI), was further up-regulated, both in vitro and in vivo detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. (nih.gov)

Human cells contain many different cyclins binding to different CDKs. (wikipedia.org)
CDKs and cyclins appear and activate at specific cell cycle phases. (wikipedia.org)
Further research has demonstrates that Cdks, cyclins and CKIs play essential roles in processes such as transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions and spermatogenesis. (wikipedia.org)
Flavopiridol is a synthetic flavone that has been postulated to be an inhibitor of cyclin-dependent kinases (CDKs) (Schmerwitz et al. (researchsquare.com)
A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, with marked potency on CDK2 and CDK9. (rcsb.org)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)

2011 ). In addition to antitumor activities, CDK inhibitors (CDKi) show prominent anti-inflammatory effects (Leitch et al. (researchsquare.com)

Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. (lsbio.com)
One of the activated genes is an inhibitor of cyclin-dependent kinases. (lsbio.com)
Genes necessary for cell cycle progression, such as E2F-dependent genes, are incorporated into the SAHF and are thereby silenced, contributing to the stability of the growth arrest. (rupress.org)
The accessibility and transcription of ribosomal genes is controlled at several levels, with their epigenetic regulation being one of the most important. (oncotarget.com)
TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)

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)

Increasingly numerous results have demonstrated overexpression of CDC2/Cyclin B1 in various tumors however there is still no report of CDC2/Cyclin B1 expression in clinical samples from patients with gliomas. (biomedcentral.com)
Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). (biomedcentral.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)

EGF-receptor and Notch signaling are antagonistic: EGF-receptor signaling leads to down-regulation of the Notch-like receptor LIN-12 , while LIN-12 signaling induces negative regulators of EGF-receptor signaling such as MAP kinase phosphatase LIP-1 and the tyrosine kinase ARK-1. (wormbook.org)
[ 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)

LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. (lsbio.com)
Resveratrol could play a toxic role through inducing apoptosis of the cancer cell in a time- and concentration-dependent manner. (mdpi.com)
Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. (biomedcentral.com)
Studies employing Bax and/or Bak knockout mouse embryonic fibroblasts (MEFs) confirm that Bax is required for ABT-737 ± roscovitine lethality, whereas Bak is primarily involved in potentiation of ABT-737-induced apoptosis by Mcl-1 down-regulation. (aacrjournals.org)
Apoptosis triggered by meriolins is accompanied by rapid Mcl-1 down-regulation, cytochrome c release, and activation of caspases. (rcsb.org)

This gene encodes the cyclin-dependent kinase inhibitor p21(WAF1/Cip1), a factor implicated in cell cycle, senescence, and cancer. (ed.ac.uk)

In the cyclin-dependent kinase (CDK) family or CDK, Cyclin, and CKIs, serine/threonine kinases play an integral role in regulating the eukaryotic cell cycle. (wikipedia.org)
Cdk5 is named after its structural similarity to members of the serine/threonine cyclin-dependent kinase family. (frontiersin.org)

It moves into the cytoplasm and eventually activates a specific cyclin-dependent kinase (CDK). (wikipedia.org)
A highly-conserved cyclin-dependent kinase that activates other CYCLIN DEPENDENT KINASES and plays a key role in regulation of the CELL CYCLE. (bvsalud.org)

Role in cancer: Cyclin-dependent kinase inhibitors (CKIs) mutants are frequent in human cancers. (wikipedia.org)
Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. (rcsb.org)

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)

CDK4/6 Inhibitors-Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer. (lillymedical.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)

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)
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)
Cdkn2a and Cdkn2b have pivotal roles in the regulation of excitotoxic RGC degeneration under NMDA-induced pathologic conditions. (elsevierpure.com)

In a genome-wide screen in vitro, we identified Combover (Cmb)/CG10732 as a novel Rho kinase substrate. (uni-wuerzburg.de)

Abnormalities in cell cycle regulation are reported to be strongly associated with tumorigenesis and progression of tumors. (biomedcentral.com)
Their de-regulation in tumors could be responsible for both a surge in ribosome biogenesis, and the loss of cell cycle control [ 1 ]. (oncotarget.com)

However, experimental approaches have limitations when dealing with complex biological systems composed of multiple layers of regulation such as the transcriptional and post-transcriptional regulation by transcription factors (TFs) and miRNAs [ 2 ]. (hindawi.com)
A network of intercellular signaling, signal transduction, and transcriptional regulation underlies the precise formation of this organ, which is the connection between the hermaphrodite uterus and the outside of the nematode. (wormbook.org)
Impact of core histone modifications on transcriptional regulation and plant growth. (helsinki.fi)

In this publication, the authors took a medicinal chemistry approach to identify an inhibitor for cyclin-dependent kinase 11 (CDK11), an understudied protein with important roles in cell cycle regulation, neuronal function and cell death. (fredhutch.org)
To reveal the roles of CDC2/Cyclin B1 in human malignant gliomas, CDC2 in glioma cell line, it was down-regulated by retrovirus vectors expressing short hairpin RNAs (shRNAs) ex vivo and in vivo. (biomedcentral.com)

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 structure of CDK2-CyclinA and p27 is determined by crystallography, demonstrating that the inhibitor of p27 stretches at the top of the Cyclin-CDK complex. (wikipedia.org)

Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)
Novo SM, Wedge SR, Stark LA. Ex vivo treatment of patient biopsies as a novel method to assess colorectal tumour response to the MEK1/2 inhibitor, Selumetinib . (ncl.ac.uk)

Dephosphorylation of inhibitor-1 at Thr 35 is equivalent to inactivation of the protein, as inhibitor-1 only serves as an inhibitor of PP-1 when phosphorylated by cAMP-dependent kinase (PKA) at Thr 35 . (elsevierpure.com)

GSK3β and Cdk5 are the two kinases in the center of research on Alzheimer's disease (AD), involved in the pathological symptoms of AD, Aβ plaque formation, tau hyperphosphorylation and neurodegeneration. (frontiersin.org)
So far, both kinases have mostly been examined in isolation, leading to a schism of the research field into defenders of the GSK3β-versus the Cdk5 hypotheses of AD. (frontiersin.org)
Inhibition of Cdk5 by olomoucine enhanced phosphorylation of kinesin, suggesting that the effect was mediated by negative regulation of other kinases. (frontiersin.org)

Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. (babraham.ac.uk)
These observations have prompted the development of small-molecule Bcl-2 inhibitors (refs. (aacrjournals.org)

2018 ). Currently, CDK9 inhibitors are considered potential treatments for inflammatory diseases (Hou et al. (researchsquare.com)

These resistance mechanisms frequently involve reinstatement of ERK1/2 signalling and BRAFi are now deployed in combination with one of three approved MEK1/2 inhibitors (MEKi) to provide more durable, but still transient, clinical responses. (babraham.ac.uk)

Cell cycle progression is stopped by Cyclin-dependent kinase inhibitor protein at the G1 phase. (wikipedia.org)
Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. (lsbio.com)
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)
Using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blots experiments, we compared changes in ETS-1 and ETS-2 expression, their protein levels, and the regulation of some of their target gene expressions at different stages of the ocular tumoral progression in the transgenic mouse model, Tyrp-1-TAg, with those in normal eyes from control mice of the same age. (molvis.org)
Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)

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)

Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. (rcsb.org)

The typical inactivation mechanism of the CDK/ Cyclin complex is based on binding a CDK inhibitor to the CDK cyclin complex and a partial conformational rotation of the CDK. (wikipedia.org)

In animals, CDK inhibitors are tightly regulated, especially by posttranslational mechanisms of which control of nuclear access and regulation of protein turnover are particularly important. (uni-bielefeld.de)

If cell mutations surpass the cell cycle checkpoints during cell cycle regulation, it can result in various types of cancer. (wikipedia.org)
These cyclin-dependent kinase inhibitor protein emerges only in their specific cell cycle phase. (wikipedia.org)
Each Cyclin/CDK complex are specific to the part of the cell cycle phase. (wikipedia.org)
Each CDK and cyclin can be identified based on the location of the cell cycle. (wikipedia.org)
Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. (rcsb.org)
The Arabidopsis thaliana homolog of yeast BRE1 has a function in cell cycle regulation during early leaf and root growth. (helsinki.fi)
Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)
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)
The defining characteristic of senescence is a highly stable cell cycle arrest, triggered by the up-regulation of cyclin-dependent kinase inhibitors such as p16 INK4a and p21 CIP1a . (rupress.org)
Similarly, depletion in the STRIPAK component STRIP1 affects activation of GCKIII kinases and cell cycle disruption through elevated expression of cyclin dependent kinase inhibitors p21 and p27, enhanced levels of which lead to a protective effect from therapeutic treatments and increased proliferation. (lu.se)

Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts. (hindawi.com)
Tissue microarrays (TMAs) including I-IV grade clinical glioma samples was used to determine the prognostic effect of the CDC2/Cyclin B1 expression in gliomas on different grades. (biomedcentral.com)
Furthermore, MJ significantly increased the expression of BCRC-3, resulting in an obvious up-regulation of p27. (biomedcentral.com)

Exogenous OGF was observed to have a dose-dependent, serum-independent, reversible, and receptor-mediated inhibitory action on cell proliferation that was dependent on RNA and protein synthesis. (nih.gov)

Epigenetic up-regulation of ribosome biogenesis and more aggressive phenotype triggered by the lack of the histone demethylase JHDM1B in mammary epithelial. (oncotarget.com)

Although microRNAs (miRNAs) are physically small, they have been shown to play an important role in gene regulation [ 1 ]. (hindawi.com)
The results indicate that certain residues that are not frequently considered in structure-aided kinase inhibitor design have an important role to play. (rcsb.org)
According to modern concepts, inflammation plays a leading role in the genesis of almost all age-dependent diseases, which ultimately lead the body to death. (vechnayamolodost.ru)
The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. (lu.se)
The tumour microenvironment (TME) contains several other cell types apart from cancer cells which play a role not only in the regulation of the environment but in response to treatments. (lu.se)

Our results suggest that ERKi, including current clinical candidates, act as 'kinase degraders', driving the proteasome-dependent turnover of their major target, ERK2. (babraham.ac.uk)

We describe here the meriolins, a new family of inhibitors of cyclin-dependent kinases (CDK). (rcsb.org)

Collectively, these findings suggest down-regulation of Mcl-1 by either CDK inhibitors or genetic approaches dramatically potentiate ABT-737 lethality through cooperative interactions at two distinct levels: unleashing of Bak from both Bcl-xL and Mcl-1 and simultaneous induction of Bak activation and Bax translocation. (aacrjournals.org)

However, changes in regulation that reduce the amount or function of the p27 protein in the nucleus are found in many types of cancer. (medlineplus.gov)

Anatomy13

Organisms7

Diseases4

Chemicals and Drugs169

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes47

Disciplines and Occupations1

Information Science3

Pathway12

Proteins8

Tumor5

Retinoblastoma Protein1

CDKs6

CDKI1

Genes5

Phosphorylation of the retinoblastoma1

Overexpression3

Tyrosine kinase2

Apoptosis5

CIP11

Serine2

Activates2

Mutants2

Phosphatase2

CDK42

CDKN2A3

Substrate1

Tumors2

Transcriptional regulation3

Roles2

Inhibit1

CDK21

Selumetinib2

Dephosphorylation1

Cdk53

Small molecule2

CDK91

MEK11

Progression5

Complexes1

Selectivity1

Inactivation1

Tightly regulated1

Cell cycle10

Expression3

Proliferation1

Epigenetic1

Role5

Clinical1

Family1

Induction1

Cancer1