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

Cyclin-dependent kinases (CDKs), are members of the serine-threonine protein kinase family and are responsible for taking control of cell cycle regulation in eukaryotic cells. (spandidos-publications.com)
CDKs show their action by interacting with cyclins and different CDK-cyclin complexes regulate the cell cycle in the G1, S and G2/M phases ( 1 ). (spandidos-publications.com)
Cyclins are central engines of cell cycle progression in conjunction with cyclin-dependent kinases (CDKs). (ox.ac.uk)
Indirubin-3-oxime (I3O), a synthetic derivative of indirubin, was originally designed as potent inhibitors of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β) for leukemia therapy. (edu.hk)
Flavopiridol is a synthetic flavone that has been postulated to be an inhibitor of cyclin-dependent kinases (CDKs) (Schmerwitz et al. (researchsquare.com)
Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. (intechopen.com)
The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)

The defining biochemical feature of this checkpoint is the activation of M-phase cyclin-CDK complexes, which phosphorylate proteins that promote spindle assembly and bring the cell to metaphase. (wikipedia.org)
The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at different checkpoints of the cell cycle. (wikipedia.org)
Early signaling proteins in the checkpoint pathway are members of a family of phosphatidylinositol 3-kinases, rad3 in yeast and ATR in vertebrates, that are believed to localize to sites of DNA damage. (wikipedia.org)
Various physiological and pathological conditions such as glucose starvation, inhibition of protein glycosylation and oxidative stress may cause an accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to the unfolded protein response (UPR) and autophagy. (spandidos-publications.com)
These proteins were rescued by the proteasome inhibitor MG132, indicating the autocatalytic degradation of F-box proteins upon loss of CSN2 or CSN5. (biomedcentral.com)
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 accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
In addition, Cyclin and CKI proteins are controlled at the level of their destruction. (intechopen.com)

This leads to stabilization and nuclear localization of FOXO3A resulting in transcriptional activation of the cyclin-dependent kinase inhibitor P27KIP1. (ku.edu)
Also, we found that the CCN5-induced PI3K-AKT inactivation leads to stabilization and nuclear accumulation of P27KIP1 resulting in cell cycle arrest of TNBC cells. (ku.edu)
However, proliferation of cardiomyocytes induced by nuclear-targeted cyclin D1 (D1NLS) stops after one or two rounds of cell cycles due in part to accumulation of p27Kip1, an inhibitor of cyclin-dependent kinase (CDK). (elsevierpure.com)
Thus, expression of S-phase kinase-associated protein 2 (Skp2), a negative regulator of p27Kip1, significantly enhances the effect of D1NLS and CDK4 on cardiomyocyte proliferation in vitro. (elsevierpure.com)
FASN blockade resulted in the increased expression and nuclear accumulation of the cyclin-dependent kinase inhibitors p21WAF1/CIP1 and p27Kip1, two critical mediators of the therapeutic effects of antiestrogen in breast cancer, while inactivating AKT, a key mediator of E2-promoted anchorage-independent growth. (elsevierpure.com)

Cdc2 activity is further regulated by phosphorylation/dephosphorylation of its corresponding activators and inhibitors. (wikipedia.org)
The cyclin D1-Cdk4 complex phosphorylates the pRB protein leading to sequential phosphorylation by cyclin E-Cdk2 and release of free E2F. (shu.edu)
Upon phosphorylation, R-SMADs form a complex with the common SMAD, SMAD4, resulting in nuclear accumulation of activated complexes. (shu.edu)
TGF-β1 acts predominantly through phosphorylation of the C-terminal MH2 domains of SMAD2 and SMAD3 via activin receptor-like kinase 5 (ALK5), of which activity is located at the C-terminal part of TGFBR1. (springer.com)
Phosphorylation at serine 15 of the human p53 tumor suppressor protein is induced by DNA damage and correlates with accumulation of p53 and its activation as a transcription factor. (uthscsa.edu)
We found a similar pattern of serine 18 phosphorylation and accumulation of p53 in response to irradiation in both control and DNA-PKcs- null MEFs. (uthscsa.edu)
In this study, we show that Tip60 is required for the early DNA damage response (DDR) to UV, including the phosphorylation of histone 2AX, c-Jun N-terminal kinases (JNKs), and ataxia telangiectasia-related substrates. (rupress.org)
We further revealed that the phosphorylation of cyclin-dependent kinase 2 (CDK2) on threonine-160 mediates the activation of mitogen-activated protein kinase 8 through receptor for activated C kinase 1, leading to JUN-dependent transcription of ACOD1 in human and mouse macrophages or monocytes. (usuhs.edu)
Inhibition of Cdk5 by olomoucine enhanced phosphorylation of kinesin, suggesting that the effect was mediated by negative regulation of other kinases. (frontiersin.org)

The main rad3 effector is the kinase Chk1, which is required for the G2-M arrest in response to DNA-damaging agents. (wikipedia.org)
E2F1 proteolysis via SCF-cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. (ox.ac.uk)
The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. (ox.ac.uk)
Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. (ox.ac.uk)
We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. (ox.ac.uk)
We observe that SCFcyclin F promotes E2F1 degradation after Chk1 inhibitors in a CDK dependent manner. (ox.ac.uk)
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)

They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
The DNA-dependent protein kinase (DNA- PK) can phosphorylate serine 15 of human p53 and the homologous serine 18 of murine p53 in vitro. (uthscsa.edu)

This gene encodes the cyclin-dependent kinase inhibitor p21(WAF1/Cip1), a factor implicated in cell cycle, senescence, and cancer. (ed.ac.uk)
SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)

Up-regulation appears to be specific to p27 because expression of cyclin D1, E, and A, and p21Cip1/Waf1 was not modulated by these agents. (biomedcentral.com)

Different phases of the cell cycle experience activation and/or deactivation of specific cyclin-CDK complexes. (wikipedia.org)
New anticancer therapy strategies refer to the inhibition of CDK-cyclin complexes as an important target to prevent uncontrolled proliferation and induce apoptosis in cancer cells ( 2 ). (spandidos-publications.com)
Transcriptional and translational control, sequestration in cyclin D1 complexes and localization all regulate p27 in G1 phase. (biomedcentral.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)

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)
Two schools of thought exist, one states that SK develops from an accumulation of senescent cells, whereas the other states that cells hyperproliferate. (globale-dermatologie.com)

b) 4-Hydroxytamoxifen (but not tamoxifen), genistein (but not genistin), daidzein, and probably other nutritional and chemopreventive anti-cancer agents could up-regulate expression of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (biomedcentral.com)
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 nucleotide potency profile and the blockade of the ADP-mediated inhibitory effect by the phospholipase C inhibitor U-73122 suggest that P2Y1 receptor controls ZL55 cell proliferation. (unisalento.it)
The promising anticancer drug milciclib potently inhibits cyclin-dependent kinase (CDK) 2 and tropomyosin receptor kinase (TRK) A, and is currently in phase II clinical studies. (srcinhibitors.com)
It potently inhibits the complex formed between cyclin-dependent kinase (CDK) 2 and cyclin A, and the tropomyosin receptor kinase (TRK) A, with a half-maximal inhibitory concentration (IC50) of 45 and 53 nM, respectively (Brasca et al. (srcinhibitors.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)

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

however, nuclear accumulations of pSMAD2-C and CLDN3 redistribution were observed with similar time course in ciliated and non-ciliated cells. (springer.com)
It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2‑α may serve important roles in adrenocortical tumor development. (cancerindex.org)

Thus, treatment with the pure antiestrogen ICI 182 780 or the potent and specific inhibitor of MEK/ERK, U0126, was sufficient to abolish the synergistic nature of the interaction between FASN blockade and E2-stimulated ERα transactivation. (elsevierpure.com)
Here we report distinct mechanisms by which the novel, potent, and selective inhibitor of the p53-MDM2 interaction HDM201 elicits therapeutic efficacy when applied at various doses and schedules. (bace-signal.com)

During the first 10 postnatal days, administration of valproic acid (VPA), the specific inhibitor for histone deacetylase activity, resulted in significant hypomyelination with delayed expression of late differentiation markers and retained expression of progenitor markers. (rupress.org)

Here, we show that persistent DNA damage accumulation in tissue-infiltrating macrophages carrying an ERCC1-XPF DNA repair defect ( Er1 F/− ) triggers Golgi dispersal, dilation of endoplasmic reticulum, autophagy and exosome biogenesis leading to the secretion of extracellular vesicles (EVs) in vivo and ex vivo. (nature.com)
The features of the senescence phenotype usually consist of the activation of a chronic DNA damage response, the involvement of various cyclin-dependent kinase inhibitors, increased secretion of proinflammatory and tissue-remodeling factors, induction of antiapoptotic genes, altered metabolic rates, and endoplasmic reticulum stress [ 13 ]. (biomedcentral.com)

In the present study, our aim was to determine the time-dependent, ER-mediated apoptotic and autophagy induction of purvalanol in HCT 116 colon cancer cells. (spandidos-publications.com)
CSN2 knockdown resulted in non-apoptotic cell death associated with accumulation of both the autophagy marker LC3-II and autophagic vacuoles. (biomedcentral.com)
Treatment of vector control K562 cells with the autophagy inhibitors 3-methyladenine and bafilomycin A1 recapitulated the growth kinetics, vacuolar morphology and LC3-II accumulation of CSN2 knockdown cells indicating that the cellular phenotype of CSN2 cells arises from autophagy inhibition. (biomedcentral.com)
An inhibitor of autophagy, 3-methyladenine (3-MA), was used to pretreat RAW 264.7 cells. (researchsquare.com)

GSK3β inhibitors but not CDK5 inhibitors reduced the neurotoxicity induced by 6OHDA. (edu.hk)
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)
Cdk5 is named after its structural similarity to members of the serine/threonine cyclin-dependent kinase family. (frontiersin.org)

Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. (ox.ac.uk)
Through the inhibition of ADP-activated transductional kinases it was found that PKC-δ was responsible for JNK1/2 activation. (unisalento.it)

These events resulted in upregulation of the Cdk4/6 inhibitor p15 INK4B and repression of the Cdk-activating phosphatase Cdc25A. (shu.edu)

In the current study, we have shown, for the first time, that I3O prevented 6-hydroxydopamine (6OHDA)-induced neuronal apoptosis and intracellular reactive oxygen species accumulation in PC12 cells in a concentration-dependent manner. (edu.hk)

p27(Kip1) is a cyclin-dependent kinase inhibitor. (biomedcentral.com)
The cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is a key cell-cycle regulator of G1-to-S phase transition [ 1 ]. (biomedcentral.com)

Accumulation of cyclin B increases the activity of the cyclin dependent kinase Cdk1 human homolog Cdc2 as cells prepare to enter mitosis. (wikipedia.org)
Purvalanol, a novel cyclin-dependent kinase inhibitor, is referred to as a strong apoptotic inducer which causes cell cycle arrest in various cancer cells such as prostate, breast and colon cancer cell lines. (spandidos-publications.com)
Olomoucine, roscovitine and purvalanol are examples of CDK inhibitors (CDKIs) designed and investigated for their apoptotic potential on cancer cells ( 3 ). (spandidos-publications.com)
It is widely recognized that the accumulation of various harmful genetic alterations in normal cells may induce malignant cancer cells ( 1 ). (spandidos-publications.com)
Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. (ox.ac.uk)
Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. (ox.ac.uk)
Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. (ox.ac.uk)
We used next-generation sequencing of lipopolysaccharide-activated THP1 cells to demonstrate that ACOD1 accumulation confers a robust proinflammation response by activating a cytokine storm, predominantly through the tumor necrosis factor signaling pathway. (usuhs.edu)
Genetic deletion of CDK2 or ACOD1 in myeloid cells, or the administration of the CDK inhibitor dinaciclib, protected mice against polymicrobial sepsis and was associated with improved survival and decreased cytokine storm. (usuhs.edu)
Precis: Pulsed high doses versus sustained low doses of the p53-MDM2 inhibitor HDM201 elicit a pro-apoptotic response from wild-type p53 cancer cells, offering guidance to current clinical trials with this and other drugs that exploit the activity of p53. (bace-signal.com)
Continuous exposure of HDM201 led to induction of p21 and delayed accumulation of apoptotic cells. (bace-signal.com)

The ability of FASN to regulate E2/ERα signaling may represent a promising strategy for anticancer treatment involving a new generation of FASN inhibitors. (elsevierpure.com)

The small compound C75, a synthetic slow-binding inhibitor of FASN activity, induced a dramatic augmentation of estradiol (E2)-stimulated, ERα-driven transcription. (elsevierpure.com)

Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. (ox.ac.uk)

Interestingly, indirubin-3-oxime and GSK3β inhibitors prevented 6OHDA-induced dysregulation of MEF2D. (edu.hk)
Therefore activities of the other kinases Erk, CK1 and GSK3β were tested after oloumucine treatment. (frontiersin.org)

inositol-requiring enzyme 1 (IRE1α), PRKR-like ER kinase (PERK) and activating transcription factor-6 (ATF-6). (spandidos-publications.com)

Rather, p53 accumulation by either knockdown of Mdm2 or addition of an Mdm2 inhibitor, Nutlin-3, before irradiation strongly attenuated the UV-induced DDR and increased cell survival. (rupress.org)

Activation of p53 by inhibitors of the p53-MDM2 interaction is being pursued as a therapeutic strategy in p53 wild-type cancers. (bace-signal.com)

During the G2 phase, Bora accumulates and forms an activation complex with Aurora A. This complex then regulates the activation of Polo-like kinase 1 (Plk1). (wikipedia.org)
Once cyclin concentration reaches a certain minimum activation threshold, Cdc2 is rapidly activated. (wikipedia.org)
In the case of unreplicated DNA, the cyclin concentration threshold for Cdc2 activation is further increased. (wikipedia.org)
Up-regulation of the expression of p27 is likely due to the activation of translation rather than transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor of transcription, did not attenuate the up-regulation of p27. (biomedcentral.com)
In this issue, we generally review the mechanisms of cellular senescence in diabetic nephropathy, which involve telomere attrition, DNA damage, epigenetic alterations, mitochondrial dysfunction, loss of Klotho, Wnt/ β -catenin signaling activation, persistent inflammation, and accumulation of uremic toxins. (hindawi.com)
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)

Through a positive feedback loop, CyclinB-Cdc2 activates the phosphatase Cdc25 which in turn deactivates the CyclinB-Cdc2 inhibitors, Wee1 and Myt1. (wikipedia.org)
The combined activity and complex of Cdc2, Cdc25, and Plk1 with the accumulation of cyclin B activates the CyclinB-Cdc2 complex, promoting entry into mitosis. (wikipedia.org)

Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, DNA damage accumulation, and expression of some SASP components. (aging-us.com)

Histone deacetylation was essential during a specific temporal window of development and was dependent on the enzymatic activity of histone deacetylases, whose expression was detected in the developing corpus callosum. (rupress.org)
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)
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)

DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)

Skp2 might be a versatile tool to improve the effect of cyclins on post-ischaemic regeneration of cardiomyocytes in vivo. (elsevierpure.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)

Our findings pave the way for patient selection in the clinical use of checkpoint inhibitors. (ox.ac.uk)

Anatomy13

Organisms9

Diseases4

Chemicals and Drugs165

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes49

Disciplines and Occupations1

Information Science3

CDKs8

Proteins8

P27KIP15

Phosphorylation9

Chk17

Protein kinase2

Cip12

WAF11

Complexes4

Senescent cells2

Receptor5

Degradation1

CDKi1

Nuclear2

Potent2

Specific inhibitor1

Secretion2

Autophagy4

CDK54

Inhibition2

Upregulation1

Reactive oxygen1

Kip12

Cells11

Anticancer1

Synthetic1

Ubiquitin ligase1

GSK32

Transcription Factor1

Knockdown1

Mdm21

Activation6

Activates2

Senescence2

Activity4

Damage1

SKP21

Therapeutic1

Clinical1