Paper degradation of cyclins. Medical search. Frequent questions

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)
In the first cycle of the bicyclic cascade model, cyclin promotes the activation of cdc2 kinase through reversible dephosphorylation, and in the second cycle, cdc2 kinase activates a cyclin protease by reversible phosphorylation. (physiomeproject.org)
That cyclin activates cdc2 kinase while the kinase triggers the degradation of cyclin has suggested that oscillations may originate from such a negative feedback loop [Felix, M. A., Labbe, J. C., Doree, M., Hunt, T. and Karsenti, E. (1990) Nature (London) 346, 379-382]. (physiomeproject.org)
This conjecture is corroborated by the model, which indicates that sustained oscillations of the limit cycle type can arise in the cascade, provided that a threshold exists in the activation of cdc2 kinase by cyclin and in the activation of cyclin proteolysis by cdc2 kinase. (physiomeproject.org)
A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase, Albert Goldbeter, 1991, Proceedings of the National Academy of Sciences , 88, 9107-9111. (physiomeproject.org)
Minimal cascade model for the mitotic oscillations between cyclin and cdc2 kinase (M) during the cell cycle. (physiomeproject.org)
The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome-mediated degradation of PDCD4. (plos.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)
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)
The level of free β-catenin is low in normal cells, since the protein is sequestered in a complex, which includes the adenomatous polyposis coli (APC) protein, a serine threonine glycogen kinase (GSK-3β) and conductin or Axin, leading to degradation of β-catenin by proteasome. (biomedcentral.com)
Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (oncotarget.com)
A multitude of pathways control cyclin-dependent kinase activities as the major event for cell cycle progression. (benthamscience.com)
In human monocytic cell lines U-937 and THP-1, LeTx induced cell cycle arrest in Go-Gi phase by rapid down-regulation of cyclin D1/D2 and checkpoint kinase 1 through MEK1 inhibition. (uwo.ca)
His study in MAP2K7 is interdisciplinary in nature, drawing from both Mitogen-activated protein kinase kinase, Cyclin-dependent kinase 9, ASK1 and MAP kinase kinase kinase. (research.com)
His work deals with themes such as MAP2K7, Cyclin-dependent kinase 2, Mitogen-activated protein kinase kinase, Untranslated region and MAP kinase kinase kinase, which intersect with Molecular biology. (research.com)

During these mitotic cycles, there are barely detectable oscillations in the total level of B-type cyclins. (vt.edu)
Numerical simulations reproduce the main features of wild-type mitotic cycles: patterns of protein accumulation and degradation, lengthening of later cycles, and arrest in interphase 14. (vt.edu)

These results reveal an unexpected role for K63-linked ubiquitin chains and UBE2N in degrader-induced proteasomal degradation and demonstrate the diversity of the ubiquitin code used for chemical hijacking. (nature.com)
In the absence of Wnt ligands, a complex containing APC, AXIN and GSK3 phosphorylates β-catenin, marking it as a substrate for ubiquitination by β-TrCP and subsequent proteasomal degradation. (plos.org)
To evaluate the capacity of the UPS to degrade disease related proteins, polyglutamine (polyGln) proteins were targeted for proteasomal degradation. (5dok.org)
However, aggregation of the aggregation- prone polyGln proteins prevented proteasomal degradation. (5dok.org)
Thus the formation of aggregates renders these toxic proteins resistant to proteasomal degradation and initiates the accumulation of polyGln proteins and polyGln-interacting proteins. (5dok.org)
A mutant form of Ub, UBB +1 is another protein that can resist proteasomal degradation. (5dok.org)
substrate that blocks proteasomal degradation. (5dok.org)
efficient proteasomal degradation. (5dok.org)

In response to genotoxicants, Cdc25A undergoes posttranslational modifications which contribute to its proteasome-mediated degradation and consequent cell cycle checkpoint arrest. (oncotarget.com)
Pulsatile shear stress induces ubiquitin-proteasome-mediated degradation of PDCD4 via a PI3K/Akt pathway in HUVECs. (plos.org)
Activated Akt inhibited GSK3 and prevented proteasome-mediated cyclin D1 degradation in LeTx-intoxicated THP-1 cells. (uwo.ca)

It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21 Cip/Waf and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. (nature.com)
In addition, cell cycle distribution analysis revealed that G0/G1 phase arrest was induced following pristimerin treatment in CAL‑27 and SCC‑25 cells, which was strongly associated with upregulation of p21 and p27, coupled with downregulation of cyclin D1 and cyclin E. Meanwhile, pristimerin induced significant apoptosis of CAL‑27 and SCC‑25 cells, alongside decreased levels of caspase‑3 and specific cleavage of poly (ADP‑ribose) polymerase. (spandidos-publications.com)

Two biochemical processes, protein phosphorylation/dephosphorylation and ubiquitin-mediated degradation drive cell cycle control. (benthamscience.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)
This weeks Arabidopsis Research Roundup begins with two papers from Royal Hollaway University of London that investigate the factors that control leaf development in the dark and the control of PIN1 phosphorylation. (garnetcommunity.org.uk)

Although two E3s, CRL2 VHL and CRL4 CRBN , frequently assemble with proteolysis-targeting chimeras (PROTACs) to attach lysine-48 (K48)-linked ubiquitin chains, the diversity of the ubiquitin code used for chemically induced degradation is largely unknown. (nature.com)
B-type cyclins are rapidly degraded in the transition between metaphase and anaphase and their ubiquitin-mediated proteolysis is necessary for cells to exit mitosis. (bibf1120.com)

Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. (hindawi.com)
UBE2N promotes degradation of cIAP1 induced by cIAP1 ligands and subsequent cancer cell apoptosis. (nature.com)
Fig. 2: UBE2N promotes degrader-induced cIAP1 degradation and apoptosis. (nature.com)

In 1990, two key papers were published that identified and characterized important dynamic relationships between cyclin and MPF in interphase-arrested frog egg extracts. (wikipedia.org)
Since the model predicts that MPF activation at the interphase-to-mitosis transition is governed by the turning point of an S-shaped curve, Novak and Tyson suggest that transition-delaying checkpoint signals biochemically move the turning point to larger values of cyclin B concentration. (wikipedia.org)
the APC then promotes cyclin degradation and resets Cdc2 to its inactive, interphase state. (sontaglab.org)

This model assumes that MPF activates cyclin degradation via APC activation, and it decouples cyclin degradation from MPF destruction. (wikipedia.org)
Goldbeter proposed a model where cyclin also catalytically activates MPF, but without an autocatalytic, positive feedback loop. (wikipedia.org)
The model describes a two-step process, where MPF first activates the APC, and then the APC drives cyclin degradation. (wikipedia.org)

The dual specificity phosphatase Cdc25A is a key regulator of the cell cycle that promotes cell cycle progression by dephosphorylating and activating cyclin-dependent kinases. (oncotarget.com)
Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis. (paganolab.org)

In the absence of cyclin E, Mcl-1 ubiquitination was enhanced, leading to decreased protein stability. (oncotarget.com)

Norel and Agur's model proposes a mechanism where cyclin catalytically drives the production of MPF, which in turn autocatalyzes. (wikipedia.org)
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)

The model pertains to the situation encountered in early amphibian embryos, where the accumulation of cyclin suffices to trigger the onset of mitosis. (physiomeproject.org)
A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of β-catenin accompanied with increased cyclin D1 expression. (biomedcentral.com)

In addition to ligand-regulated degradation of β-catenin, Wnt signaling is antagonized by extracellular factors that inhibit the ability of Wnt ligands to bind to Fzd and initiate signaling, such as the secreted frizzled-related proteins (SFRP1, WNT inhibitory factor (WIF) and dickkopf (DKK) [3] . (plos.org)
Extracellular matrix stiffness regulates degradation of MST2 via SCF-βTrCP. (paganolab.org)

Overview of the Nabet Lab's research that develops and utilizes protein degradation strategies to destroy cancer-causing proteins. (fredhutch.org)
When added to other proteins, ubiquitin has the ability to mark them for degradation and recycling. (georgetown.edu)
Yarden's lab discovered that BRCA1 targets two specific proteins cyclin B and Cdc25c, which are the "keeper genes" that regulate the G2/M checkpoint - the last checkpoint a cell has to go through before it divides. (georgetown.edu)
The paper shows that in response to DNA damage, BRCA1 is responsible for tagging these two proteins to stop the cells from dividing so repair can occur," Yarden said. (georgetown.edu)
These studies focus on the degradation of specific disease related proteins and the general status of the UPS under conditions of an excess of aberrant or misfolded proteins. (5dok.org)
Since the UPS is also responsible for the degradation of ER proteins we investigated the effect of ER stress on the functionality of the UPS. (5dok.org)
However, in these diseases the UPS is compromised and some proteins might resist degradation. (5dok.org)
degradation of polyglutamine proteins. (5dok.org)
The differences in p53 expression and cyclin D1 expression seen between high and low risk HPV infection, reflect the known differences between high and low risk types and are in agreement with the known differences between high risk and low risk E6 and E7 proteins. (st-andrews.ac.uk)

Flavopiridol is a synthetic flavone that has been postulated to be an inhibitor of cyclin-dependent kinases (CDKs) (Schmerwitz et al. (researchsquare.com)
The penultimate paper is led by Richard Napier from the University of Warwick and determines the parameters that define the substrates of the AUX1 protein whilst the final paper includes Cyril Zipfel (TSL) as a co-author and uses systems biology approaches to characterise the interactions between leucine-rich repeat receptor kinases (LRR-RKs). (garnetcommunity.org.uk)

Fig. 6: Generality of UBE2N-mediated (neo-)substrate degradation. (nature.com)

The analysis shows how miototic oscillations may readily arise from time lags associated with these thresholds and from the delayed negative feedback provided by cdc2-induced cyclin degradation. (physiomeproject.org)

Tyson neglected the role of MPF in activating the APC, assuming that only a phosphorylated form of cyclin was rapidly degraded. (wikipedia.org)
Remarkably, protein degradation occurs rapidly, in as little as 15-20 minutes. (fredhutch.org)

Degradation of neo-substrates directed by cIAP1-recruiting PROTACs also depends on UBE2N. (nature.com)

Specifically, Nabet has developed a chemical-genetic technology with similar functionality to PROTACs called the degradation tag (dTAG) system. (fredhutch.org)

No relationship was observed between the expression pattern of β-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. (biomedcentral.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)
Cyclin E knock-down restored ABT-737 sensitivity to acquired and inherently resistant Mcl-1-dependent tumor cells. (oncotarget.com)

In Tyson's 1991 model, cyclin is a stoichiometric activator of Cdc2, as cyclin binds with phosphorylated Cdc2 to form preMPF, which is activated by Cdc25 to generate MPF. (wikipedia.org)
Cdc2 regulation also involves positive feedback4, with active Cdc2-cyclin B stimulating its activator Cdc25 and inactivating its inhibitors Wee1 and Myt1. (sontaglab.org)

It employs concepts seen in the previous models such as stoichiometric binding of Cdc2 and cyclin B, positive feedback loops through Cdc25 and Wee1, and delayed activation by MPF of the APC, but includes additional reactions such as that of Wee1 and Cdc25. (wikipedia.org)

Felix's paper looked at cyclin B degradation in these extracts and found that MPF degrades cyclin B in a concentration dependent and time-delayed manner. (wikipedia.org)
The Novak-Tyson model, first published in the paper titled "Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos", builds on the Goldbeter and Tyson 1991 models in order to generate a unifying theory, encapsulating the observed dynamics of the cyclin-MPF relationship. (wikipedia.org)

According to the Novak-Tyson model, rather than describing Solomon's observations as a sigmoidal switch as seen in the Goldbeter model, the threshold behavior of cyclin concentration dependent MPF activity is instead, a discontinuity of a bistable system. (wikipedia.org)

This disease impacts all joint tissues and is characterized by progressive cartilage degradation, synovitis, abnormal subchondral bone remodeling, and osteophyte formation [ 2 ]. (aging-us.com)

In this study, we investigated the expression pattern of β-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the β-catenin gene and Axin gene in esophageal squamous cell carcinoma. (biomedcentral.com)
Cyclin D1 is expressed in the G1 phase of the cell cycle, and is thought to play a major role in the control of the cell cycle and cancer progression. (biomedcentral.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)
Xiao (cell department routine) mutants and determined a book mutant (and so are mixed up in degradation of Clb2 and the merchandise of both genes associate using the candida APC. (bibf1120.com)

Cytostatic factor (CSF), which prevents the degradation of cyclin B and maintains high maturation-promoting factor (MPF) activity, is required for maintenance of metaphase I-arrest in LT oocytes, similar to its requirement for maintaining metaphase II-arrest in normal oocytes. (jax.org)
It is therefore hypothesized that the observed delay in acquisition of competence to enter anaphase I may instigate the sustained metaphase I-arrest in LT oocytes by allowing CSF activity to rise to a level that prevents cyclin B degradation and maintains high MPF activity before anaphase can be initiated by normal triggering mechanisms. (jax.org)
The binding of HPV E6 to p53, and its subsequent targeting for degradation, prevents activation of the p53 pathway in HPV infected cells. (st-andrews.ac.uk)

Plasticity of the cullin-RING ligase repertoire shapes sensitivity to ligand-induced protein degradation. (nature.com)

This negative regulation of DNA-PKcs by depleting PIG3 seemed to take place at the translational level but not at the levels of transcription or protein degradation. (ijbs.com)

D-Index & Metrics D-index (Discipline H-index) only includes papers and citation values for an examined discipline in contrast to General H-index which accounts for publications across all disciplines. (research.com)

Solomon's paper showed a distinct cyclin concentration threshold for the activation of MPF. (wikipedia.org)
When graphing the MPF activity with respect to cyclin concentration, the model shows a sigmoidal shape, with a hypersensitive, threshold region similar to what was observed by Solomon. (wikipedia.org)
However, this model depicts an effectively asymptotic plateau behavior at cyclin concentrations above the threshold, whereas the observed curve shows a steady increase in MPF activity at cyclin concentrations above the threshold. (wikipedia.org)

The findings presented suggest that the mechanisms employed by low risk HPV6 or HPV11 to subvert cellular functions in condylomata acuminata are similar to those employed by high risk HPVs, with the exception of cyclin D1 and p53 protein over-expression. (st-andrews.ac.uk)

The full text of research papers can be submitted to the repository via Pure , the University's research information system. (st-andrews.ac.uk)

This paper examined whether Cdc2 activation is bistable, confirming that the response of Cdc2 to non-degradable cyclin B is temporally abrupt and switchlike, as would be expected if Cdc2 activation were bistable. (sontaglab.org)

Feature papers represent the most advanced research with significant potential for high impact in the field. (mdpi.com)

The purpose of this paper is to provide a review of site-specific treatment options that involve the targeting of angiogenesis in gynecologic malignancies. (cancernetwork.com)
In this paper we introduce a new cross-category similarity measurement called CroGO by incorporating genome-specific gene co-function network data. (biomedcentral.com)
Discriminative SKP2 interactions with CDK-cyclin complexes support a cyclin A-specific role in p27KIP1 degradation. (paganolab.org)

This subsequently causes the degradation of the AuxIAA protein, setting off a cascade of auxin-dependent transcriptional responses. (garnetcommunity.org.uk)

11. Amsel, A. & Roussel, J. Motivational properties of ences in post-transcriptional processes spark interest in the development of frustration: I. Effect on a running response of the (protein redistribution, degradation), pharmacotherapies that selectively reg- addition of frustration to the motivational com- plex. (lu.se)
Third is a paper from Bristol that demonstrates the translation of research from Arabidopsis into coriander with regard the control of the response to UV light. (garnetcommunity.org.uk)

However, this model is unable to recreate the observed cyclin dependent MPF activity relationship seen in Solomon's 1990 paper, as it shows no upper steady-state level of MPF activity. (wikipedia.org)
En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)

Christine Foyer (Leeds) leads the next paper that defines the relationship between cold treatment and strigolactone signalling. (garnetcommunity.org.uk)

Then, the discussion about the photocatalytic activity of the AgNPs (either in suspension or impregnation), and correlation with your properties and its potential application to organic pollutants degradation under UV and visible/solar radiation will be described. (intechopen.com)
The filters were assayed for β-gal activity by freezing them in liquid nitrogen thawing them and incubating them on Whatman paper soaked in Z buffer plus 5-bromo-4-chloro-3-indolyl β-d-galactoside US Biological. (bibf1120.com)

A Feature Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for future research directions and describes possible research applications. (mdpi.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)

These competing theories all attempted to model the experimental observations seen in the 1990 papers regarding the cyclin-MPF network. (wikipedia.org)
In this paper, we propose a dynamical model for the molecular events underlying these early nuclear division cycles in Drosophila. (vt.edu)
The CellML model runs in OpenCell to reproduce figure 3 of the published paper. (physiomeproject.org)

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. (paganolab.org)

Feature papers are submitted upon individual invitation or recommendation by the scientific editors and must receive positive feedback from the reviewers. (mdpi.com)

Anatomy19

Organisms15

Chemicals and Drugs116

Analytical, Diagnostic and Therapeutic Techniques and Equipment24

Phenomena and Processes74

Disciplines and Occupations2

Technology, Industry, Agriculture1

Information Science4

Health Care3

Kinase15

Mitotic2

Proteasomal degradation8

Proteasome-mediated3

Downregulation of cyclin2

Ubiquitin-mediated degradation1

Phosphorylation2

Proteolysis2

Apoptosis3

Interphase3

Activates3

Promotes2

Ubiquitination1

Mechanism2

Accumulation2

Extracellular2

Proteins9

Kinases2

Substrate1

Oscillations1

Rapidly2

Substrates1

PROTACs1

Tumor3

Activator2

Cdc251

Extracts2

Goldbeter1

Abnormal1

Cell4

Prevents3

Sensitivity1

Regulation1

Metrics1

Threshold3

Expression1

Research Papers1

Activation1

High1

Specific3

Cascade1

Response2

Level2

Relationship1

Activity2

Involves1

Cells1

Model3

Phase1

Positive1