Cyclin dependent kinase inhibitor checkpoint kinase 2. Medical search. Frequent questions

Cyclin-dependent kinase 2 (CDK2), a member of Cyclin-dependent kinases (CDKs), plays an important role in cell division and DNA replication. (mdpi.com)
The G1 checkpoint is regulated by a multitude of molecules such as the retinoblastoma family of proteins, cyclins, cyclin dependent kinases (CDKs) and cyclin dependent kinase inhibitors (CDKis). (temple.edu)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
Cyclin dependent kinases (CDKs) phosphorylate several substrates such as transcription factors and cytoskeletal proteins, which leads to the transition of the cell into the next cell cycle phase. (onkoview.com)
CDKs are activated by cyclins, which are expressed in distinct phases during the cell cycle. (onkoview.com)
Importantly, CDKs are inhibited by specific cyclin dependent kinase inhibitors. (onkoview.com)
Initiation of DNA replication is certainly triggered with the actions of at least two pieces of proteins kinase Rabbit Polyclonal to CEBPG actions, cyclin-dependent kinases (CDKs) and Dbf4p-Cdc7p. (pkc-inhibitor.com)
Targeting cyclin dependent kinases (CDKs) and cell cycle checkpoint proteins can induce cell cycle arrest and apoptosis in cancer cells. (ucc.ie)

Decreased phosphorylation of ATM target proteins p53, checkpoint kinase 2 (Chk2), and histone 2A variant led to decreased DNA repair by nonhomologous end-joining. (bvsalud.org)
The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
These genes encode for closely related GTPase proteins responsible for signal transduction within two main pathways, the mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase pathways, involved in the regulation of cell growth, survival, and differentiation. (oaepublish.com)
Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. (hindawi.com)
The foundation recognition complicated (ORC), a six-subunit initiator proteins (2), exists in both pre- and post-RCs (10), and among its functions is definitely to mark the positioning of replication roots in the genome. (pkc-inhibitor.com)
Predicated on series commonalities between Cdc6p, replication aspect C, and various other AAA+ family and on the characterization of the dominant-negative mutant, it's been suggested that fungus Cdc6p might work as an ATP-dependent MCM proteins loader (45, 63). (pkc-inhibitor.com)
Several genetic alterations have been described in SCCHN, including mutations in the p53 tumor suppressor gene and mutations in genes that encode cell cycle proteins such as p16 and cyclin D1. (oncotarget.com)
This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS. (bvsalud.org)

Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. (hindawi.com)
Recent reports have indicated that terpinen-4-ol exerts its antitumor effects by triggering caspase-dependent apoptosis in human melanoma cells or by inducing necrotic cell death and cell-cycle arrest in mouse mesothelioma and melanoma cell lines without affecting normal cells [ 14 , 15 ]. (hindawi.com)
Our results indicated that terpinen-4-ol induced apoptosis through a mitochondria-mediated pathway in NSCLC cells and that the apoptosis elicited by terpinen-4-ol was p53 dependent. (hindawi.com)
It abrogates a DNA damage checkpoint (G2-phase), leading to apoptosis in combination with several DNA-damaging agents selectively in p53-deficient tumor cell lines. (activebiopharma.com)
p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. (lu.se)
Cell phone routine analyses suggest M-VCR-R is considered the most powerful mix in triggering reduction in G0/G1, G2/M arrest, overriding the spindle checkpoint resulting in elevated apoptosis currently-reliant manner (Figure 3B). (immune-source.com)
Pacritinib is an equipotent inhibitor of FLT3 and JAK2, which can be good at lessening JAK2/STAT5 and FLT-3 JAK2 signaling in FLT3 and JAK2 mutant tissues, respectively.33 A combination of pracinostat and pacritinib resulted in synergistic effects using a complete inhibition of downstream STAT5 signaling, an elevated effectiveness on cellular proliferation and the induction of apoptosis. (immune-source.com)
Analysis of synchronized HeLa cells demonstrated that endogenous bcl-2 is phosphorylated in a G 2 /M cell cycle- dependent manner without apoptosis. (johnshopkins.edu)
In addition, we confirmed that the death-decision of paclitaxel-induced apoptosis is not mediated by bcl-2 phosphorylation and believe that this decision may be mediated by the activated spindle assembly checkpoint. (johnshopkins.edu)
CDK7 silencing and CDK7 inhibitor THZ1 elicited apoptosis and suppressed tumor growth. (biomedcentral.com)
Cycloheximide or Chk2 inhibitor pretreatment abrogated not only activation of Chk2 but also G 2 /M arrest and apoptosis mediated by DIM. (aspetjournals.org)
Blocking ROS generation by N -acetyl cysteine protects the cells from DIM-mediated G 2 /M arrest and apoptosis. (aspetjournals.org)
Treating SCCHN cell lines with a pan-Aurora kinase inhibitor resulted in defective cytokinesis, polyploidy and apoptosis, which was effective irrespective of the EGFR status. (oncotarget.com)
Our results demonstrate that combined targeting of EGFR and Aurora kinases represents a therapeutic means to activate cell cycle checkpoints and apoptosis in SCCHN. (oncotarget.com)

We show that GH suppresses epithelial DNA damage repair and blocks ataxia telangiectasia mutated (ATM) kinase autophosphorylation with decreased activity. (bvsalud.org)
Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)

KRAS is regulated by tyrosine kinase receptors and, in turn, activates the MAPK signaling pathway that is mainly involved in determining cell survival, leading to a strong promotion of cell growth and replication. (oaepublish.com)
Immunotherapy (IO) plus tyrosine kinase inhibitor (TKI) has become the first-line treatment for advanced renal cell carcinoma, despite the lack of prognostic biomarkers. (e-crt.org)
Recently, clinical trials of immune checkpoint inhibitor plus vascular endothelial growth factor receptor-tyrosine kinase inhibitor (TKI) for mRCC have exhibited outstanding efficacies [ 3 - 5 ]. (e-crt.org)
Inhibiting WEE1 abrogates G2 cell cycle arrest, resulting The tyrosine kinase WEE1 regulates cyclin-dependent kinase in premature entry into mitosis and leading to aberrantly 1 (CDK1), which drives cells from the G2 phase into mitosis, high CDK2 activity in S-phase cells, with the deregulated and CDK2, which drives cells into and through the S phase DNA replication resulting in replication stress [1, 5]. (sagepub.com)
Tagrisso, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is the first medication approved to treat patients with non-small cell lung cancer (NSCLC) who develop resistance to first-line TKIs due to the development of the EGFR T790M mutation. (pharmacytimes.com)

Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)
Thus, WEE1 inhibition sensitizes cancers have loss-of-function TP53 mutations, meaning that tumor cells to DNA-damaging chemotherapy and can lead to they become more dependent on the G2/M- and S-phase unstable DNA replication, DNA damage and mitotic catas- checkpoints to halt progression of the cell cycle [3, 4]. (sagepub.com)
Launching of hMcm protein onto chromatin takes place in past due mitosis concomitant using the devastation of cyclin B, indicating that the mitotic kinase activity inhibits prereplication complicated formation in individual cells. (pkc-inhibitor.com)
Besides its function in DNA replication, it could also be engaged inside a mitotic checkpoint control, because Cdc6-deprived candida cells that usually do not replicate DNA still go through a reductional mitosis (4, 47, 63). (pkc-inhibitor.com)

The cyclin D1-Cdk4 complex phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. (shu.edu)
It abolishes cyclin-dependent kinase 1 (CDC2) activity by phosphorylation of the Tyr15 residue. (activebiopharma.com)
It really has been demonstrated formerly that phosphorylation of H3 (on S10) contributes to improved productivity of your following H3 acetylation, contributing to synergistic modifications of gene expression.44 Pacritinib, and also aiming for JAK2, can be a potent FLT3 inhibitor. (immune-source.com)
Both LNCaP and HeLa cells were continuously exposed to clinically achievable concentrations of paclitaxel and observed for activation of programmed cell death as measured by cytotoxic dose-response curves, poly(adenosine diphosphate-ribose) polymerase cleavage, bcl-2 phosphorylation, and the activation of caspase-7 (interleukin-1 beta converting enzyme (ICE)-LAP3). (johnshopkins.edu)
Initially, we asked whether paclitaxel-induced bcl-2 phosphorylation is triggered by the spindle assembly checkpoint via an active cdc2 kinase-dependent pathway and whether phosphorylation of endogenous bcl-2 is the signal that activates cell death machinery. (johnshopkins.edu)
Paclitaxel-induced G 2 /M cell cycle arrest correlated with cdc2 kinase activity and bcl-2 phosphorylation. (johnshopkins.edu)
Olomoucin, a specific inhibitor of cyclin-dependent kinases, inhibited bcl-2 phosphorylation. (johnshopkins.edu)
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)
Our results reveal the specific and essential functions of Cdk2 inhibitory phosphorylation in the successful execution of the replication stress checkpoint response and in maintaining genome integrity. (cancerrealitycheck.com)
The persistent fork progression in HU-treated Cdk2AF/AF cells indicates that Cdk2 inhibitory phosphorylation is required for normal Corynoxeine execution of the S-phase checkpoint induced by replication stress. (cancerrealitycheck.com)

We prove that You-2932, TMD-8, and Granta-519 tissues (Kitchen table 2) co-express Myc and Bcl2 inside an energetic BCR signaling pathway (Physique 1). (immune-source.com)

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors synergistically increased the effectiveness of antiprogrammed cell death protein-1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) antibodies in preclinical studies. (bmj.com)
Methods This non-randomized, multicohort, phase II study evaluated the efficacy and safety of the anti-PD-1 antibody nivolumab 240 mg administered every 2 weeks in combination with the CDK4/6 inhibitor abemaciclib 150 mg twice daily and either fulvestrant (FUL) or letrozole (LET) as a first-line or second-line treatment for HR-positive HER2-negative metastatic breast cancer. (bmj.com)
These events resulted in upregulation of the Cdk4/6 inhibitor p15 INK4B and repression of the Cdk-activating phosphatase Cdc25A. (shu.edu)
P15 INK4 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclind-CDK4,6, inhibiting it from hypophosphorylating Rb, thereby, rendering the cell cycle unresponsive to external proliferation signals. (shu.edu)
Full holoenzyme activity of the cyclin D1-Cdk4 complex is induced by mitogen recruitment of CAK. (shu.edu)
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)
ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. (biomedcentral.com)
Our study aimed to investigate CDK4/6 inhibitors and their ability to inhibit cell cycle progression. (ucc.ie)
We specifically chose CDK4/6 inhibitors as they have proven to be quite effective in previous studies of breast cancer(9). (ucc.ie)
We used Palbociclib (PAL), a CDK4 inhibitor which causes cell cycle arrest at G1 and prevents cells progressing to S phase. (ucc.ie)

The suppressive effect of PD-1 on Skp2 expression was mediated by inhibition of both PI3K/Akt and Ras/MEK/Erk pathways and was only partially reversed by IL-2, which restored activation of MEK/Erk but not Akt. (shu.edu)
ABT-869 , VX-680 or sunitinib), leads to an upregulation of JAK2 exercise, triggering second resistance.33 For that reason, although combinations of FLT3 inhibitors and HDACi happen to be described to exhibit synergy in vitro,23, 24 this mixture without having the more JAK2 inhibition can result in opposition after chronic dosing and not show improved effectiveness from the in vivo placing. (immune-source.com)
CDK7 inhibition sensitized NSCLC to p38α inhibitor. (biomedcentral.com)
The tumor suppressor protein p53 is inhibition also exploits the G1 checkpoint deficiency seen involved in regulation of the G1 checkpoint. (sagepub.com)
In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. (biomedcentral.com)
Combined Aurora kinase and EGFR targeting using a monoclonal anti-EGFR antibody was more effective compared to single EGFR and Aurora kinase inhibition. (oncotarget.com)

In contrast, downstream signaling from ATR directly to the checkpoint kinase Chk1 was required for survival responses for a smaller subset of the drugs tested. (ascopost.com)

The RAS gene family, responsible for signal transduction within the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways, is frequently involved in carcinogenesis, and alterations in its member genes can be detected, with variable frequency, in a wide variety of solid and hematological cancers. (oaepublish.com)

MK-1775 is a potent and selective Wee1 kinase inhibitor with an IC50 of 5.2 nM. (activebiopharma.com)
Bang, Yung-Jue 2020-02-07 00:00:00 Background The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. (sagepub.com)
WEE1 of the cell cycle [1, 2]. (sagepub.com)
Adavosertib (AZD1775) is a first-in-class, potent, selec- Electronic supplementary material The online version of this tive WEE1 inhibitor. (sagepub.com)

Background Hormone receptor (HR)-positive breast cancer is a disease for which no immune checkpoint inhibitors have shown promise as effective therapies. (bmj.com)
Moreover, PD-1 and PD-L1 inhibitors are being tested in combination with other checkpoint inhibitors, targeted therapies, cancer vaccines, monoclonal antibodies, and other modalities. (shu.edu)
Recently, immune checkpoint blockade therapies (ICBs) targeting PD-1/PD-L1 axis have exhibited significant clinical benefits. (biomedcentral.com)
[1] Thus metronomic therapies, which are known to be directed toward the tumor microenvironment [2] may play an important role in improving the outcome of patients with CCa. (ganzemedizin.at)

Immunotherapy mainly includes immune checkpoint inhibitors (ICIs), such as inhibitors of PD-1 (programmed cell death 1)/programmed cell death ligand 1 (PD-L1). (nature.com)
In order to cure metastatic disease, several approaches are imaginable: (1) locoregional treatment of the primary tumor and all metastatic sites, (2) tumor eradication by excellent systemic anticancer therapy, (3) long-term immunologic tumor control induced by immunotherapy or (4) the combination of these approaches. (springer.com)

To further establish the involvement of Chk2 in DIM-mediated G 2 /M arrest, cells were transfected with dominant-negative Chk2 (DN-Chk2). (aspetjournals.org)
Blocking Chk2 activation by DN-Chk2 completely protected cells from DIM-mediated G 2 /M arrest. (aspetjournals.org)
These results clearly indicate the requirement of Chk2 activation to cause G 2 /M arrest by DIM in ovarian cancer cells. (aspetjournals.org)

In breast cancer patients, it is unclear whether measuring p53, mdm-2, or p21 expression provides information on how patients will respond to chemotherapy. (lu.se)
p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. (lu.se)

Although immune checkpoint inhibitors (ICIs), in particular blockade of PD-1/PD-L1, show promising therapy response in some cancers, they are less effective in PCa which may be poor infiltration of cytotoxic T-cells [ 7 - 9 ]. (thno.org)

Remedy with alisertib up-controlled outrageous style p53 in Granta-519 MCL cells specifying G0/G1 arrest consequent to G2/M checkpoint activation. (immune-source.com)
Growth-inhibitory effects of DIM were mediated by cell cycle arrest in G 2 /M phase in all the three cell lines. (aspetjournals.org)

We analyzed the clinical data and performed immunohistochemistry for Epidermal growth factor receptor (EGFR) and Aurora kinase A (Aurora-A) expression in 180 SCCHN patients. (oncotarget.com)
Comparing pan-Aurora kinase and Aurora-A targeting hints towards a strong and clinically relevant biological effect mediated via Aurora kinase B. Taken together, our findings characterize a new poor risk group in SCCHN patients defined by elevated EGFR and Aurora-A protein expression. (oncotarget.com)

In this regard, they noted that dactinomycin and bortezomib (Velcade), for example, induced a similar dependence on ATR pathways for cell growth after treatment, despite having highly dissimilar mechanisms of action-a finding suggesting that "there may be many avenues by which ATR inhibitors might provide enhanced therapeutic effects. (ascopost.com)
Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)

Receptor-regulated SMADs (R-SMADs), SMAD1, 2, 3, 5, and 8, are the only SMADs directly phosphorylated and activated by the kinase domain of type I receptors. (shu.edu)
The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. (lookformedical.com)
Novartis) for the first-line treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced breast cancer. (pharmacytimes.com)

Other G 2 /M regulatory molecules such as Cdc25C, Cdk1, cyclin B1 were down-regulated by DIM. (aspetjournals.org)

The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. (biomedcentral.com)

CAOV3 cells, which are atRA sensitive, have been shown to express p16INK4a (p16), a cyclin dependent kinase inhibitor regulating the G1 checkpoint. (temple.edu)

Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.com)
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)

For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
[ 2 ] Targeted disruption of TP53 in the mouse leads to the development of various tumors (see image below). (medscape.com)
DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)

Cyclin-dependent kinase 5 (CDK5) affects the tumor microenvironment, which may influence the efficacy of TKI+IO. (e-crt.org)

Moreover, the identification of fork protection as a key mechanism of resistance to chemo- and poly (ADP-ribose) polymerase inhibitor therapy in ovarian cancer further increases the priority that should be accorded to the development of strategies targeting replicative stress. (bmj.com)
DIM treatment inhibited the growth of SKOV-3, TOV-21G, and OVCAR-3 ovarian cancer cells in both a dose- and time-dependent manner with effective concentrations ranging from 40 to 100 μM. (aspetjournals.org)

Works in various organisms have revealed that the kinase is involved in centrosome separation, duplication and maturation as well as in bipolar spindle assembly and stability. (lookformedical.com)

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)
Here we address the posttranslational regulation of INHIBITOR/INTERACTOR OF CDK 1 (ICK1)/KIP RELATED PROTEIN 1 ( KRP1), an Arabidopsis ( Arabidopsis thaliana) CDK inhibitor. (uni-bielefeld.de)
The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. (lu.se)
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
ST also caused the depolarization of mitochondrial membrane potential and increased Bax/Bcl-2 protein ratio. (biomedcentral.com)

In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)
Orderly progression through the cell cycle involves passage through sequential checkpoints. (shu.edu)
Despite improvements in survival through early detection and treatment, rapid disease recurrence and progression still plague some patients [ 2 ]. (hindawi.com)
Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
There is a pressing need to improve therapy in particular for patients with metastatic disease or local recurrence, where the median progression-free and overall survival is only ~ 6 months and ~11 months, respectively [ 2 - 4 ]. (oncotarget.com)

Within this analysis, we reveal the efficiency and tolerability from the pan HDACi pracinostat in different in vitro and also in vivo types of AML, and display synergistic benefits at a number of concentrations in conjunction with the JAK2/FLT-3 inhibitor pacritinib in both the in vitro and also in vivo placing. (immune-source.com)
This means that that synergy between a JAK2 inhibitor along with an HDACi might also operate in microscopic cells that happen to be fully reliant on JAK2 (wt) signaling. (immune-source.com)
Consistent because of this, related in vitro synergy was discovered within the JAK2 wt Establish-2 tissue and F36-P microscopic cells but not in FLT3 mutant mobile product lines using the precise pan-JAK inhibitor ruxolitinib in conjunction with pracinostat (records not demonstrated). (immune-source.com)
Our party recently discovered that treatment of FLT3-ITD tissue with FLT3 inhibitors inadequate JAK2 process (e.g. (immune-source.com)

Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. (mdpi.com)
Recently, the first crystal structure of CDK2 with allosteric inhibitor has been reported, which provides new opportunities to design pure allosteric inhibitors of CDK2. (mdpi.com)
p27 is a cyclin dependent kinase inhibitor that blocks the activity of Cyclin E-CDK2, which phosphorylates pRb, thereby ushering the cell from G1 into S phase through the Restriction point (Figure 2). (shu.edu)
It also blocks Cyclin A-CDK2 from further phosphorylating pRb to maintain S phase. (shu.edu)
It was found that activation of the upstream kinase S-phase-specific cyclin-dependent kinase (Cdk) 2 was required for robust activation of ATR in response to numerous and diverse chemotherapeutic agents, and that Cdk2-mediated ATR activation promoted cell survival after treatment with many drugs. (ascopost.com)

Vincristine [VCR] is energetic with the IC50 of .59 to 2.75 nM in most DLBCL tissue and also the conjunction with alisertib [M] was highly synergistic (Body 2, Dinner table 3). (immune-source.com)

The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. (lookformedical.com)

These data suggest that the combined CDK7 inhibitor THZ1 and antiPD-1 therapy can be an effective treatment in NSCLC. (biomedcentral.com)
Alecensa is an oral TKI approved for the second-line treatment of patients with anaplastic lymphoma kinase (ALK) positive NSCLC. (pharmacytimes.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)

2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China. (thno.org)

Those transformed cells form tumours when implanted in immunodeficient mice, indicating that the kinase is an oncogene. (lookformedical.com)
Cdk2AF cells also exhibited strikingly abnormal responses to replication stress accumulated irreparable DNA damage and permanently exited the cell cycle after transient exposure to S-phase inhibitors. (cancerrealitycheck.com)
For growth assays cells were seeded on day 0 at 2 0 cells per well in a 96-well plate. (cancerrealitycheck.com)
Based on previous studies we predicted that PANC-1 cells would be most resistant to drug treatment followed by BxPC-3 and MIAPaCa-2 cells. (ucc.ie)
Our hypothesis was that using a cell cycle inhibitor as a pre-treatment to ECT would make cells more susceptible to treatment. (ucc.ie)

WT mice exhibit age-dependent colon DNA damage accumulation, while in aged mice devoid of colon GH signaling, DNA damage remains low, with elevated p53. (bvsalud.org)
role of each cyclin in the Cdk2AF DNA damage phenotype. (cancerrealitycheck.com)

However, when the disease progresses to castration-resistant prostate cancer (CRPC), there are limited treatments for those patients and lead to dissatisfied outcomes [ 2 , 3 ]. (thno.org)
p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical methods in primary tumors derived from 134 patients who took part in a randomized multicenter trial comparing docetaxel to sequential methotrexate and 5-fluorouracil (MF) in advanced breast cancer. (lu.se)
So far, unfortunately, checkpoint inhibitors as monotherapy have led to responses only in a small percentage of patients with metastatic breast cancer. (springer.com)
The investigators suggested that, on the basis of findings in their study, "If these inhibitors prove to be sufficiently specific, they may facilitate many potential combinatorial strategies that may be broadly applicable to many types of cancer. (ascopost.com)
RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. (biomedcentral.com)
An important development in cancer research over the past 2 decades has been the recognition that genetic changes drive the pathogenesis of tumors of both adulthood and childhood. (medscape.com)
The male-to-female ratio in head and neck cancer is 2:1. (medscape.com)
Skin cancer is the major cutaneous malignancy and about 76,250 people are estimated to be diagnosed for skin cancer in 2013 [ 2 ]. (biomedcentral.com)

Hypoxia and genetic defects that chronically drive proliferation leave such tumors dependent on a steady supply of nutrients, especially glucose. (springer.com)
Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. (lu.se)

Ectopic kinase overexpression in any culture cell line leads to polyploidy and centrosome amplification. (lookformedical.com)

PD-1 suppressed the transcription of SKP2 , the substrate recognition component of the SCF Skp2 ubiquitin ligase that leads p27 kip1 to degradation and resulted in accumulation of p27 kip1 (Figure 2). (shu.edu)
The mouse Tzfp gene, mapped to chromosome 7 B2-B3, encodes a 465-amino acid transcription factor containing a conserved N-terminal BTB/POZ domain and three C-terminal PLZF-like C(2)H(2) zinc fingers. (lookformedical.com)

Orkambi is an oral combination tablet that treats the underlying disease in cystic fibrosis patients aged 12 and older who have 2 copies of the F508del mutation in their cystic fibrosis transmembrane conductance regulator gene. (pharmacytimes.com)

In mobile phone proliferation assays, Granta-519 and OCI-Ly10 tissue have related IC50s in the plethora of 37 to 110 nM compared to You-TMD and 2932Number 2). (immune-source.com)

In these measurements, constant holding at −60 mV for 59 s, then a depolarizing step to +100 mV for 1 s was applied to activate ci-VSP and induce PI(4,5)P 2 hydrolysis. (bioz.com)

Anatomy12

Organisms5

Diseases3

Chemicals and Drugs160

Analytical, Diagnostic and Therapeutic Techniques and Equipment12

Phenomena and Processes61

Disciplines and Occupations1

Information Science3

Health Care1

CDKs8

Proteins8

Apoptosis14

Ataxia telangi2

Tyrosine5

Mitotic7

Phosphorylation10

Signaling pathway1

CDK410

Inhibition6

CHK11

PI3K1

WEE14

Therapies4

Immunotherapy2

Chk23

Chemotherapy2

ICIs1

Arrest2

EGFR2

Therapeutic2

Receptor3

CDK11

Regulates1

P16INK4a1

MITOSIS3

TP533

Tumor microenvironment1

Ovarian cancer2

Spindle assembly1

Protein5

Progression5

JAK24

CDK25

IC501

Upstream1

NSCLC2

Cancers1

Regulation1

Cells5

Damage2

Cancer8

Tumors2

Polyploidy1

Transcription2

Gene1

Proliferation1

Activate1