KinasesCDKsMitosisInhibitorsDegradationClb2ProgressionPhosphorylationUbiquitinationMitotic cyclinsLevels of cyclinProteinsInactivationRegulationAccumulationKinase promotesSubcellular localizationMetaphase-anaphase transitionCdk1PeptidesDependentSubstratesGeneModulateInhibitionTranscriptionOverexpressionSubstrateGenesTurnover1993PhaseAbsencePeptideCells
Kinases12
- Cyclins are central engines of cell cycle progression in conjunction with cyclin-dependent kinases (CDKs). (ox.ac.uk)
- Cell-cycle events are controlled by cyclin-dependent kinases (CDKs), whose periodic activation is driven by cyclins. (nature.com)
- Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. (nature.com)
- Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
- Protein stability is dependent on amino acid limitation and cis signals within Gcn4p which are recognized by cyclin-dependent protein kinases, including Pho85p. (uni-luebeck.de)
- A driving force of the cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors. (scienceopen.com)
- His laboratory showed that cyclin-dependent kinases prevent pre-RC assembly in budding yeast by inhibiting ORC, and by regulating Cdc6 proteolysis and Mcm2-7 nuclear localisation. (royalsociety.org)
- A relatively well understood example is the network that controls progression of the cell cycle, where cyclin-dependent kinases (CDKs) couple with various cyclins over the cell cycle to regulate critical processes [ 2 - 4 ]. (biomedcentral.com)
- however, the cyclin B/CDK1 complex is kept inactive because CDK1 is phosphorylated at the inhibitory sites threonine 14 (T14) and tyrosine 15 (Y15) by the kinases WEE1 and MYT1. (endocrinology-journals.org)
- Access into S-phase and mitosis in the eukaryotic cell routine is controlled with the activation of cyclin-dependent kinases (CDKs). (bio2009.org)
- Cyclins bind to and regulate the activity of the Cyclin Dependent Protein Kinases (CDKs). (ximbio.com)
- 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)
CDKs1
- 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)
Mitosis4
- Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (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)
- Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. (ximbio.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)
Inhibitors6
- Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. (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)
- Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
- This led to an intensive development of small-molecule CDK9 inhibitors or new emerging strategies, such as proteolysis targeting chimeras (PROTACs). (rsc.org)
- Recent studies have shown that cyclin-dependent kinase (CDK) inhibitors can have a tremendous impact on cell cycle progression in plants. (uni-bielefeld.de)
- In Arabidopsis thaliana, the SIAMESE-RELATED proteins (SIM/SMR1 to 13) are a plantspecific family of Cyclin-dependent Kinase Inhibitors (CKIs), homologous to the Kip-Related Proteins. (hal.science)
Degradation5
- We conclude that Mad2 delays the onset of cyclin B and securin degradation and averts aneuploidy during meiosis I in mammalian oocytes. (ncl.ac.uk)
- β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
- The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. (ox.ac.uk)
- The second option entails ubiquitin-mediated degradation of B-type cyclins which requires the cyclosome (Sudakin et al. (bio2009.org)
- 3) Clnp-Cdc28p protein kinase phosphorylates the cyclin-dependent kinase inhibitor (CKI) Sic1p focusing on it for ubiquitin-mediated degradation via the ubiquitin-conjugating enzyme Cdc34p (Schwob et al. (bio2009.org)
Clb22
- Here we compare the specificity of two budding yeast cyclins, the S-phase cyclin Clb5 and the M-phase cyclin Clb2, in the phosphorylation of 150 Cdk1 (Cdc28) substrates. (nature.com)
- Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
Progression3
- 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)
- The ubiquitin-mediated proteolysis of cyclin E plays a central role in cell-cycle progression, and cyclin E accumulation is a common event in cancer. (rcsb.org)
- Cyclin A is involved in the regulation of the cell cycle and is essential for progression through S phase. (ximbio.com)
Phosphorylation5
- β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. (ox.ac.uk)
- the cyclin B-cdk 1 complex) is activated at M-phase onset by removal of inhibitory phosphorylation of cdk1 at thr-14 and tyr-15. (ox.ac.uk)
- By sampling extracts at very short intervals during both meiotic and mitotic exit, we found that cyclin B1-associated cdk1 underwent transient inhibitory phosphorylation at tyr-15 and that cyclin B1-cdk1 activity fell more rapidly than the cyclin B1 content. (ox.ac.uk)
- Treatment of M-phase extracts with a mutant cyclin B1-cdk1AF complex, refractory to inhibition by phosphorylation, impaired binding of the Anaphase Promoting Complex/Cyclosome (APC/C) to its co-activator Cdc20 and altered M-phase exit. (ox.ac.uk)
- Thus, CDK1 undergoes transient, inhibitory WEE1-dependent tyrosine 15 phosphorylation before substantial inactivation by cyclin B proteolysis. (endocrinology-journals.org)
Ubiquitination2
- A model that explains the role of multiple cyclin E/Sic1 degrons is provided by the findings that Fbw7 and Cdc4 dimerize, that Fbw7 dimerization enhances the turnover of a weakly associated cyclin E in vivo, and that Cdc4 dimerization increases the rate and processivity of Sic1 ubiquitination in vitro. (rcsb.org)
- Taken together, our results demonstrate that the exposure of cells to cadmium chloride resulted in cytotoxicity and cell death due to enhanced ubiquitination and consequent proteolysis of eIF4E protein, which in turn diminished cellular levels of critical genes such as cyclin D1. (cdc.gov)
Mitotic cyclins2
- It has been suggested that once cells pass Start, Cln proteolysis is triggered by the mitotic cyclins Clb1, 2, 3 and 4 (ref. 6). (uky.edu)
- The anaphase promoter complex (APC) is a multiprotein complex - an ubiquitin E3 ubiquitin ligase - involved in ubiquitin-dependent proteolysis of cell cycle regulatory proteins, and in which we include the destruction of mitotic cyclins during the metaphase-anaphase transition. (fapesp.br)
Levels of cyclin2
- Exposure of cells to cadmium , as well as the specific silencing of eIF4E gene, also resulted in decreased cellular levels of cyclin D1, a critical cell cycle and growth regulating gene, suggesting that the observed inhibition of cyclin D1 gene expression in the cadmium -treated cells is most likely due to decreased cellular level of eIF4E. (cdc.gov)
- The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
Proteins9
- Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. (wikipedia.org)
- Proteolysis can also be used as an analytical tool for studying proteins in the laboratory, and it may also be used in industry, for example in food processing and stain removal. (wikipedia.org)
- Limited proteolysis of a polypeptide during or after translation in protein synthesis often occurs for many proteins. (wikipedia.org)
- Proteolysis can, therefore, be a method of regulating biological processes by turning inactive proteins into active ones. (wikipedia.org)
- 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)
- We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. (biomedcentral.com)
- The SIM/SMRs proteins are good candidates to link cell cycle activity with environmental stimuli.This research work has shown the involvement of the UPS proteolysis in the posttranslational control of all the tested members of the SIM/SMR family. (hal.science)
- In budding fungus activation of S-phase Clbp-Cdc28p proteins kinase depends upon the last activation of Cdc28p connected with another course of G1 cyclins Cln1-3p. (bio2009.org)
Inactivation2
- Thus, timely M-phase exit requires a tight coupling of proteolysis-dependent and proteolysis-independent mechanisms of MPF inactivation. (ox.ac.uk)
- The systems ensuring the timely inactivation and activation of cyclin B-CDK in G1 have been studied primarily in budding candida. (bio2009.org)
Regulation3
- Consequently, abnormality in the regulation of proteolysis can cause disease. (wikipedia.org)
- however, the mechanisms underlying the regulation of cyclin F are poorly understood. (ox.ac.uk)
- Our data suggest that transcriptional induction of the Atf3 gene in maturing chondrocytes results in down-regulation of cyclin D1 and cyclin A expression as well as activation of RUNX2-dependent transcription. (biomedcentral.com)
Accumulation2
Kinase promotes1
- Additionally, cyclin-dependent kinase promotes initiation by phosphorylating Sld2 and Sld3. (royalsociety.org)
Subcellular localization1
- GSK-3 has been shown to regulate cyclin D1 proteolysis and subcellular localization (5). (cellsignal.com)
Metaphase-anaphase transition1
- Cyclosome-mediated proteolysis is definitely activated in the metaphase-anaphase transition and its activity is managed during early G1 where it contributes to the prevention of a premature rise of Clbp-Cdc28p kinase activity (Irniger et al. (bio2009.org)
Cdk11
- Targets of the cyclin-dependent kinase Cdk1. (nature.com)
Peptides1
Dependent8
- Schulman, B. A., Lindstrom, D. L. & Harlow, E. Substrate recruitment to cyclin-dependent kinase 2 by a multipurpose docking site on cyclin A. (nature.com)
- Cyclin dependent kinase 9 (CDK9) plays an essential role in regulating transcriptional elongation. (rsc.org)
- The protein encoded by this gene is a cyclin-dependent kinase 2 (CDK2) -associated protein which is thought to negatively regulate CDK2 activity by sequestering monomeric CDK2, and targeting CDK2 for proteolysis. (cancerindex.org)
- Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. (cancerindex.org)
- At M-phase exit, MPF is destroyed by ubiquitin-dependent cyclin proteolysis. (ox.ac.uk)
- Start is triggered by the cyclin- dependent kinase Cdc28 and three rate-limiting activators, the G1 cyclins Cln1, Cln2 and Cln3 (ref. 3). (uky.edu)
- We had shown earlier that transcription of the cell cycle genes cyclin D1 and cyclin A in chondrocytes is dependent on CREs. (biomedcentral.com)
- Endothelin receptor type B (EDNRB) deleted in colorectal carcinoma (DCC) and cyclin-dependent kinase inhibitor 2A (CDKN2A or p16) were screened for hypermethylation in serum from HNSCC patients and normal control volunteers. (hiv-proteases.com)
Substrates1
- Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. (ox.ac.uk)
Gene3
- In Lamivudine IC50 fission candida the CKI encoded from the rum1 gene takes on a crucial part in regulating the cyclin B-CDK activity in G1 (Moreno and Nurse 1994 blue right-pointing triangle). (bio2009.org)
- Duplication of CCND1 gene was attributed to some of the cases with cyclin D1 expression. (biomedcentral.com)
- The underlying mechanism for cyclin D1 expression was due to an abnormal gene rearrangement involving BCL-6 and CCND1, which was different from most reported cases. (biomedcentral.com)
Modulate1
- A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
Inhibition4
- 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)
- Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. (ox.ac.uk)
Transcription1
- Repression of cyclin A transcription by ATF3 required the CRE in the cyclin A promoter. (biomedcentral.com)
Overexpression2
- Proteolysis of cyclin B and securin commenced earlier in Mad2-depleted oocytes, resulting in a shortened duration of meiosis I. Furthermore, overexpression of Mad2 inhibited homolog disjunction. (ncl.ac.uk)
- The phenotype and genetic abnormalities of DLBCL with cyclin D1 overexpression can be complex and may be difficult to differentiate from blastoid and pleomorphic variants of mantle cell lymphoma. (biomedcentral.com)
Substrate1
- Finally, we examine co-clustering of the CDK consensus motifs with the 'cy' or RXL motif [ 17 ], which is known to be important in determining which CDK-cyclin complex will phosphorylate a given substrate. (biomedcentral.com)
Genes1
- The identification of the complete set of genes encoding the APC subunits in Arabidopsis, suggests that the basic processes controlled by ubiquitin-mediated proteolysis in plants are similar to those of other organisms. (fapesp.br)
Turnover1
19931
- Schwob and Nasmyth 1993 blue right-pointing triangle) and 2) inactivates Clbp proteolysis (Amon et al. (bio2009.org)
Phase4
- There is certainly significant overlap between mitotic and S-phase B-cyclins (Schwob et al. (bio2009.org)
- Cyclin A protein is absent in cells prior to S-phase, during which its levels increase and peak. (ximbio.com)
- Cyclin A is a marker for actively proliferating cells and for cells in S phase. (ximbio.com)
- As suggested by our cell cycle analysis Oxi 4503 data Sch B arrested HCCC-9810 and RBE cells at the G0/G1 phase (Fig. 3A) which may be due to the downregulation of cyclin D1 and CDK4. (hiv-proteases.com)
Absence1
- However, rare DLBCLs may show cyclin D1 expression in absence of t (11,14)(q13;q23) or SOX11 expression. (biomedcentral.com)
Peptide1
- This signal peptide is removed by proteolysis after their transport through a membrane. (wikipedia.org)
Cells1
- Further study showed that Sch B treatment resulted in a downregulation of the Oxi 4503 expression of cyclin D1 and CDK4 in both HCCC-9810 and RBE cells (Fig. 3C). (hiv-proteases.com)