Ubiquitin ligase degradation of mitotic cyclins. Medical search. Frequent questions

The ubiquitination of mitotic cyclins continues along with that of APC/CCDH1-specific targets such as the yeast mitotic spindle component, Ase1, and cdc5, the degradation of which is required for the return of cells to the G1 phase. (wikipedia.org)
Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (intechopen.com)
Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
Using a computational model based on multi-step ubiquitination, we then show how changes in the interaction between a single substrate and APC/C Cdc20 can alter the timing of degradation onset relative to APC/C Cdc20 activation, while ensuring a fast degradation rate. (biomedcentral.com)
The degradation timing of APC/C Cdc20 substrates depends on the multi-step nature of ubiquitination, differences in substrate-APC/C Cdc20 interactions, and competition among substrates. (biomedcentral.com)
CUL4A acts as a scaffold proteins to create a CUL4A-DDB1-Band complicated and regulates many mobile pathways by concentrating on a number of protein for ubiquitination and degradation. (healthandwellnesssource.org)
We have also provided evidence that CUL4A-mediated RASSF1A ubiquitination occurs during mitotic phase of the cell cycle and CUL4A suppresses the ability. (healthandwellnesssource.org)
The E3 ubiquitination step determines the overall specificity for ubiquitination of the target protein, and the activated ubiquitin is usually transferred to a lysine residue in the substrate. (bmbreports.org)
In the absence of cyclin E, Mcl-1 ubiquitination was enhanced, leading to decreased protein stability. (oncotarget.com)
During growth, genes associated with protein ubiquitination/deubiquitination, cell cycle progression, and proteasomal degradation were affected, while genes linked to protein and carbohydrate catabolism were affected during early development. (frontiersin.org)

The phosphorylation of the protein targets of M-Cdks (Mitotic Cyclin-dependent Kinases) drives spindle assembly, chromosome condensation and nuclear envelope breakdown in early mitosis. (wikipedia.org)
The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
This degradation is mediated by at least two domains indicating the presence of at least two different pathways impinging on ICK1/KRP1 protein stability. (uni-bielefeld.de)
We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. (biomedcentral.com)
The COP9/signalosome (CSN) is a highly conserved eight subunit complex that, by deneddylating cullins in cullin-based E3 ubiquitin ligases, regulates protein degradation. (biomedcentral.com)
The two main routes for eukaryotic intracellular protein clearance are the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. (biomedcentral.com)
The E3 ligase interacts with the protein substrate and thus confers the specificity of the UPS [ 16 ]. (biomedcentral.com)
The largest known class of E3 ubiquitin ligases comprises the Cullin-RING ligases (CRLs) of which the best studied is the SCF (Skp1, Cul1, F-box protein) complex [ 16 ]. (biomedcentral.com)
The covalent attachment of ubiquitin to a target protein is catalyzed by the sequential action of a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). (bmbreports.org)
Here, we show that cyclin E/Cdk2 phosphorylates and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). (oncotarget.com)
Cyclin E depletion in various human tumor cell-lines and cyclin E -/- mouse embryo fibroblasts showed decreased levels of Mcl-1 protein, with no change in Mcl-1 mRNA levels. (oncotarget.com)
intramitochondrial protein for a ligase on lung. (erik-mill.de)
So if we think about the ubiquitin system, so proteins are degraded and on the right side you see that each protein is kept at a level and the level can be dynamic, it can fluctuate. (lindau-nobel.org)
But if something wrong does happen, the protein can be excessively degraded and something, it will go below its steady state level or there will be a mutation in a recognition site of a ligase that was mentioned to you by Avram. (lindau-nobel.org)
Or in the recognition motif of the substrate, it makes it associating with the ligase and then the protein will accumulate. (lindau-nobel.org)
Let it be either excessive degradation or under degradation of a protein. (lindau-nobel.org)
Don't be dragged behind me by this over simplification, not in all cases the proper degradation is the primary cause but this aggregation and accumulation of protein always plays a pathogenetic role. (lindau-nobel.org)
system_update_alt데이터시트system_update_alt안전 데이터시트Overview 개요Product Name:Human SPAG5(sperm associated antigen 5) ELISA KitProduct Code:HUFI03067Size:96 AssaysAlias:Astrin, Deepest, Mitotic spindle-associated protein p126, MAP126Detection method:Sandwich. (assaygenie.kr)
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 hallmark of proteome balance is the ubiquitin-proteasome system (UPS) that degrades roughly 80% of multi-ubiquitinated proteins ( Collins and Goldberg, 2017 ). (elifesciences.org)
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 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 phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
The APC/C is an E3 ubiquitin ligase that drives mitotic progression by promoting timely degradation of key regulatory proteins [ 3 ]. (biomedcentral.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)
The regulated expression and degradation of proteins are critical to all aspects of cell development and proliferation. (biomedcentral.com)
A key component involved in regulating degradation of proteins by the UPS is the COP9 signalosome (CSN). (biomedcentral.com)
This review focuses on an up-to-date understanding of the functions of E3 ligases in cancers and debates the perspectives of cancer cells that rely on inhibition or activation of ubiquitylation of target proteins. (bmbreports.org)
E3 ligases consist of a large family of more than 600 proteins ( 3 ), and a few E3 ligases have been classified based on their conserved structural domains (e.g. (bmbreports.org)

Cyclins are targeted for proteolytic degradation by the anaphase promoting complex (APC), also known as the cyclosome, a ubiquitin-ligase. (wikipedia.org)
The active, CDC20-bound APC (APC/CCDC20) targets mitotic cyclins for degradation starting in anaphase. (wikipedia.org)
Experimental addition of non-degradable M-cyclin to cells induces cell cycle arrest in a post-anaphase/pre-telophase-like state with condensed chromosomes segregated to cell poles, an intact mitotic spindle, and no reformation of the nuclear envelope. (wikipedia.org)
However, the existence of differential phases to cdc14 activity between anaphase and telophase is suggestive of additional, unexplored late-mitotic checkpoints. (wikipedia.org)
Complete release and maintained activation of cdc14 is achieved by the separate Mitotic Exit Network (MEN) pathway to a sufficient degree (to trigger the spindle disassembly and nuclear envelope assembly) only after late anaphase. (wikipedia.org)
The breaking of the mitotic spindle, common to the completion of mitosis in all eukaryotes, is the event most often used to define the anaphase-B to telophase transition, although the initiation of nuclear reassembly tends to precede that of spindle disassembly. (wikipedia.org)
These changes are orchestrated by a small number of master regulators, including the cyclin-dependent kinases (Cdks) and the anaphase-promoting complex/cyclosome (APC/C). Each Cdk or APC/C isoform has a large number of substrates, and the substrates of each isoform are modified in a specific order that leads to sequential substrate activation or inactivation. (biomedcentral.com)
Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cyclosome) and results in the proteasomal destruction of the separase inhibitor securin 1 . (nature.com)
Several mechanisms have already been identified because of its actions on cell routine control for instance RASSF1A-mediated G1/S cell routine arrest continues to be from the inhibition of cyclin D1 accumulating in the nucleus (15) and M-phase of cell routine legislation is certainly from the capability of RASSF1A to modulate the experience of anaphase-promoting complicated (16) and microtubule dynamics (8 11 -14). (healthandwellnesssource.org)

Ubiquitin Proteasome System Current Insights into Mechanism Cellular Regu. (intechopen.com)
Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. (intechopen.com)
These chains are recognized by the proteasome, leading to substrate degradation [ 11 ]. (biomedcentral.com)
ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
Our studies show that RASSF1A is ubiquitinated and degraded via proteasome-dependent mechanism by the CUL4A·DDB1 E3 ligase complex. (healthandwellnesssource.org)
Finally, consistent with the differential expression of genes associated with proteasomal degradation in cln5 - cells, we also observed elevated amounts of a proteasome subunit and reduced proteasome 20S activity during cln5 - growth and starvation. (frontiersin.org)

Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
Since that time several RASSF1A kinases are also discovered including cyclin-dependent kinase-4 (18) PKC (19) MST1 (macrophage stimulating-1) (20) and Aurora-B (21) that have different results on RASSF1A function. (healthandwellnesssource.org)

Deletions of multiple GID subunits compromise cell proliferation, and this defect is accompanied by deregulation of critical cell cycle markers such as the retinoblastoma (Rb) tumor suppressor, phospho-Histone H3 and Cyclin A. We identify the negative regulator of pro-proliferative genes Hbp1 as a bonafide GID/CTLH proteolytic substrate. (elifesciences.org)
And what I want to show you today is this applied side of the ubiquitin proteolytic system. (lindau-nobel.org)

Here, we used experimental and computational approaches to dissect the quantitative mechanisms underlying the ordered degradation of the substrates of the ubiquitin ligase APC/C Cdc20 , a key regulator of chromosome segregation in mitosis. (biomedcentral.com)
The activator Cdc20 is then replaced by a second activator, Cdh1, and APC/C Cdh1 promotes complete degradation of M cyclin, followed by polo-like kinase 1, Aurora A, and other substrates, to complete mitosis and cytokinesis and drive progression into G1 [ 1 , 2 ]. (biomedcentral.com)
We additional display that CUL4A-mediated RASSF1A degradation takes place during depletion and mitosis of CUL4A markedly reverses mitotic-phase-stimulated RASSF1A degradation. (healthandwellnesssource.org)
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)

Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. (innatedb.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)
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)

CRL4-AMBRA1 is a master regulator of D-type cyclins. (paganolab.org)
A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. (paganolab.org)
DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. (virosin.org)

Particularly in yeast, an organism where gluconeogenesis and glycolytic activity are intermittently coordinated, the multi-subunit GID E3 ligase complex specifically targets the surplus of gluconeogenic enzymes, including the conserved Fructose-1,6-bisphosphatase 1 (Fbp1), for proteasomal degradation. (elifesciences.org)

During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
Paradoxically, progression deeper into cell cycle arrest was accompanied by increases in proliferative effectors such as CDKs and cyclins, which can drive cell cycle re-entry by overcoming p21 induction. (bvsalud.org)

Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C) , two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. (sdbonline.org)

Degradation timing and dynamics depend on substrate affinity for the enzyme as well as the catalytic rate at which the substrate is modified. (biomedcentral.com)
We show experimentally that increased expression of the early APC/C Cdc20 substrate Clb5 does not delay the degradation of the later substrate securin, arguing against a role for competition with Clb5 in establishing securin degradation timing. (biomedcentral.com)
Specific substrates generally bind with sufficient affinity that they remain bound during multiple ubiquitin transfer reactions, resulting in processive substrate modification [ 9 , 10 ]. (biomedcentral.com)
The CUL4A EPZ005687 E3 ligase provides the E2 and substrate in close closeness where ubiquitin could be transferred from the E2 to the substrate (22 23 Some of the known CUL4A substrates include DDB2 (24) Cdt1 (25 26 HOXA9 (22 23 and c-Jun (27) and they have a diverse cellular functions such as DNA repair and replication cell differentiation and transcription regulation (23). (healthandwellnesssource.org)

Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers, resulting in impaired apoptosis. (oncotarget.com)

EPZ005687 CUL4A E3 ligase is certainly a member from the cullin E3 ligase family members (22). (healthandwellnesssource.org)

Extracellular matrix stiffness regulates degradation of MST2 via SCF-βTrCP. (paganolab.org)

In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)

Telophase is primarily driven by the dephosphorylation of mitotic cyclin-dependent kinase (Cdk) substrates. (wikipedia.org)
Depending on how APC/C Cdc20 is partitioned among its substrates, competition can have minor or major effects on the degradation of certain substrates. (biomedcentral.com)

CSN5 knockdown caused mitotic defects, G2/M arrest and apoptotic cell death. (biomedcentral.com)

Blocking cdc14 activation in these cells results in the same phenotypic arrest as does blocking M-cyclin degradation. (wikipedia.org)
Several recent research including ours show that RASSF1A induces cell routine arrest in both G1/S- and mitotic (M)-stages (8 11 -16). (healthandwellnesssource.org)
Three molecular mechanisms involved in tumor dormancy have been identified: cellular dormancy (quiescence or mitotic arrest), angiogenic dormancy (limited tumor size), and immunologic dormancy (immunosurveillance, balance between clearance and proliferation) (Figure 1 ). (biomedcentral.com)

Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis. (paganolab.org)

In yeast, the glucose-induced degradation-deficient (GID) E3 ligase selectively degrades superfluous gluconeogenic enzymes. (elifesciences.org)

The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. (wikipedia.org)

The requirement for phosphatase activation can be seen in budding yeast, which do not have redundant phosphatases for mitotic exit and rely on the phosphatase cdc14. (wikipedia.org)

2006. Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis. (virosin.org)

In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)

Discriminative SKP2 interactions with CDK-cyclin complexes support a cyclin A-specific role in p27KIP1 degradation. (paganolab.org)

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)

Biochemical reconstitution demonstrates that the mammalian complex possesses inherent E3 ubiquitin ligase activity, using Ube2H as its cognate E2. (elifesciences.org)

The life of a gene product, from transcription to degradation, is controlled by a series of regulatory decisions. (biomedcentral.com)

We list the DNA repair genes and related E3 ligases. (bmbreports.org)
The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)

These filaments also bind and recruit cofactors whose activities help execute abscission and/or delay abscission timing in response to mitotic errors via the NoCut/Abscission checkpoint. (elifesciences.org)

Anatomy14

Organisms11

Diseases3

Chemicals and Drugs135

Analytical, Diagnostic and Therapeutic Techniques and Equipment20

Phenomena and Processes68

Information Science3

Health Care2

Ubiquitination10

Protein19

Proteins11

Anaphase9

Proteasome6

Kinases2

Proteolytic2

Mitosis4

Pathway1

Inhibitors2

Regulator2

Genomic3

Multi-subunit1

Progression2

Subunits1

Substrate4

Kinase activity1

Cullin1

Regulates1

Inhibition1

Substrates2

Defects1

Arrest3

Signaling1

Enzymes1

Spindle1

Yeast1

Apoptosis1

Cell cycle1

Complexes1

Nuclear1

Mammalian1

Transcription1

Genes2

Checkpoint1