• These checkpoints' cell cycle blocks at both the G1/S and G2/M checkpoints are consistent with the inhibition profile of the enzymes. (wikipedia.org)
  • On the contrary, if the sequence complementarity is imperfect, there will be no degradation of the mRNA but an inhibition of its translation into protein [2]. (longlonglife.org)
  • The cell growth inhibition by CNPY2 knockdown was rescued by AR overexpression. (oncotarget.com)
  • Together, these results suggested that CNPY2 promoted cell growth of PC cells by inhibition of AR protein degradation through MYLIP-mediated AR ubiquitination. (oncotarget.com)
  • Survivin belongs to the family of inhibitors of apoptosis proteins (IAPs) that plays a pivotal role in mitotic progression, apoptosis inhibition, angiogenesis, progression of cancer, and invasion [ 5 ]. (springeropen.com)
  • In a quiescent state, it negatively regulates cell proliferation through the inhibition of the G1 to S phase transition to allow repair of DNA damages [ 7 ]. (springeropen.com)
  • In whole cells, Dox treatment prevented p34cdc2 kinase dephosphorylation without altering its synthesis, and this effect was due to neither down-regulation of cdc25C nor inhibition of protein-tyrosine phosphatase activity. (aspetjournals.org)
  • Our data suggest that translational inhibition of B-cyclin expression represents a third mechanism, in addition to cyclin degradation and Rum1 inhibition, that contributes to Cdc2 inactivation as cells exit from the mitotic cell cycle and prepare for meiosis. (ox.ac.uk)
  • The inhibition of Torc1 by rapamycin mimics nutrient starvation and causes an array of physiological changes that include global changes in gene expression, phosphorylation/dephosphorylation of various factors, decreased cell growth, degradation of proteins, and ultimately cell cycle arrest in the G 1 phase [4, 9-11]. (researchsquare.com)
  • 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)
  • 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)
  • We record for the very first time that a group of chalcone-derivatives PJ34 missing aminoacidic components right here termed RAMBs are ubiquitin-proteasome program (UPS)-stressors via inhibition of ubiquitin-mediated proteins degradation upstream from the 20S proteasomal catalytic activites. (immune-source.com)
  • Cell cycle progression is stopped by Cyclin-dependent kinase inhibitor protein at the G1 phase. (wikipedia.org)
  • A multitude of pathways control cyclin-dependent kinase activities as the major event for cell cycle progression. (benthamscience.com)
  • During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
  • Use of the triple-negative TMX2-28 breast cancer cell line to address the role of SKP2 in cell cycle progression confirmed that SKP2 contributes to a more rapid cell cycle progression and may regulates pSer10p27 levels. (umass.edu)
  • Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of tumors and may contribute to tumorigenesis. (genetex.com)
  • Although live imaging has provided extensive insights into this relationship at the single-cell level, the limited number of fluorescent markers that can be used in a single experiment has hindered efforts to link the dynamics of individual proteins responsible for decision making directly to cell cycle progression. (cam.ac.uk)
  • I will present an all-in-one cell cycle reporter that allows simultaneous analysis of cell cycle progression, including the transition into quiescence, and the dynamics of individual fate determinants. (cam.ac.uk)
  • β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
  • The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. (creative-biolabs.com)
  • Both proteins may play a role in UC progression and can have a value as prognostic and/or diagnostic markers of UC, as well as targeted therapies. (springeropen.com)
  • We studied the effect of doxorubicin (Dox) on cell cycle progression and its correlation with DNA damage and cytotoxicity in p53-mutant P388 cells. (aspetjournals.org)
  • In untreated control P388 cells, p34cdc2 kinase localizes in the nucleus and cytoplasms, particularly in the centrosomes, and p34cdc2 kinase activity is dependent on cell cycle progression, with the enzyme activity increasing steadily from G1/S to G2/M and markedly declining thereafter. (aspetjournals.org)
  • Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. (platcovid.com)
  • Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
  • CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
  • While several studies addressed how cell motility parameters change throughout the cell cycle, the relationship between invadopodia and cell cycle progression has not been elucidated. (biorxiv.org)
  • Cell cycle progression is faster in cells in which invadopodia are abolished (by Tks5 knockdown), evidenced by earlier induction of cyclins A and B. A close look at the regulators of G1 revealed that the overexpression of p27 kip1 , but not p21 cip1 , causes faster turnover of invadopodia and increased ECM degradation. (biorxiv.org)
  • Taken together, these findings suggest that invadopodia function is tightly linked to cell cycle progression and is controlled by specific cell cycle regulators. (biorxiv.org)
  • Progression through mitosis is driven by a complex set of protein-protein interaction reactions and their regulations that change over time. (pharmafocusasia.com)
  • Increased levels of polyamines in cells are considered to be involved in cancer progression. (spandidos-publications.com)
  • Introduction Ubiquitin-dependent protein degradation via the ubiquitin-proteasome system (UPS) is crucial for the Cxcr4 regulation of many cellular processes including cell cycle progression differentiation and apoptosis in both normal and cancer cells [1]. (immune-source.com)
  • Dysregulated autophagy in pancreatic β cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. (frontiersin.org)
  • Conclusion: p63, p16, MIB, Cal A, Cys A are markedly expressed and p16 is strongly suppressed in oral cavity tumors, which suggests that the latter protein may play a role in negative regulation of cell cycle progression. (bvsalud.org)
  • Immunohistochemical identification of molecular genetic events in the progression of preneoplastic lesions to spindle cell squamous-cell carcinoma enables early detection of lesions with the potential for malignant progression, thus permitting timely intervention 1,2 . (bvsalud.org)
  • The various markers that enable assessment of the progression of preneoplastic lesions to spindle cell carcinoma include the p16 protein, which halts the cell cycle and induces apoptosis by pRb-mediated phosphorylation of cyclin-dependent kinase 4 (CDK4). (bvsalud.org)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • Two biochemical processes, protein phosphorylation/dephosphorylation and ubiquitin-mediated degradation drive cell cycle control. (benthamscience.com)
  • This phosphorylation event is associated with increased cell proliferation and poor prognosis in patients with glioma. (umass.edu)
  • β-TrCP recognizes cyclin F through a non-canonical degron site (TSGXXS) after its phosphorylation by casein kinase II. (ox.ac.uk)
  • This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. (creative-biolabs.com)
  • The accumulation of hTopBP1 on chromatin and its subsequent interaction with hRad9 lead to cell cycle arrest, a process mediated by Chk1 phosphorylation and ataxia telangiectasia and Rad3-related protein (ATR) activation. (biomedcentral.com)
  • Mitochondria, a powerhouse of the cell, are rich in a large number of enzymes, which not only participate in cellular oxidative phosphorylation and ATP synthesis, but also regulate intracellular calcium ions and reactive oxygen species to maintain cellular homeostasis. (biomedcentral.com)
  • Moreover, our data show an increase in glycogen synthase kinase-3beta activity, which triggers phosphorylation-dependent cyclin D1 degradation. (unife.it)
  • A reduction in cdk4 protein levels is also observed with a parallel reduction in Rb phosphorylation levels at Ser-780. (unife.it)
  • HCT 116 colon cancer cells were exposed to purvalanol, which activated ER stress via upregulation of PERK, IRE1α gene expression, eIF-2α phosphorylation and ATF-6 cleavage at early time-points in the HCT 116 colon cancer cells. (spandidos-publications.com)
  • In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. (nature.com)
  • The N-terminal phosphorylation of RB by p38 bypasses its inactivation by CDKs and prevents proliferation in cancer cells. (nature.com)
  • A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin-dependent kinase (CDK) and Cyclin activity by stopping the cell cycle if there are unfavorable conditions, therefore, acting as tumor suppressors. (wikipedia.org)
  • Cyclin-dependent kinase inhibitor proteins are essential in the regulation of the cell cycle. (wikipedia.org)
  • Cyclin-dependent kinase inhibitor proteins work by inactivating the CDKs by degradation. (wikipedia.org)
  • The typical inactivation mechanism of the CDK/ Cyclin complex is based on binding a CDK inhibitor to the CDK cyclin complex and a partial conformational rotation of the CDK. (wikipedia.org)
  • Cyclin-dependent kinase inhibitor proteins use ATP as a phosphate contributor to phosphorylate serine and threonine residues. (wikipedia.org)
  • Seven cyclin-dependent kinase inhibitor proteins have been identified. (wikipedia.org)
  • These cyclin-dependent kinase inhibitor protein emerges only in their specific cell cycle phase. (wikipedia.org)
  • The discovery of Cyclin-dependent kinase inhibitor proteins in 1990 opened the door in how we think about cell cycle control. (wikipedia.org)
  • In mammals, p27, a cyclin-dependent kinase inhibitor protein, helps control CDK activity in G1. (wikipedia.org)
  • The structure of CDK2-CyclinA and p27 is determined by crystallography, demonstrating that the inhibitor of p27 stretches at the top of the Cyclin-CDK complex. (wikipedia.org)
  • S-phase kinase-associated protein 2 (SKP2) is an important cell cycle regulator, targeting the cyclin-dependent kinase (CDK) inhibitor p27 for degradation, and is frequently overexpressed in breast cancer. (umass.edu)
  • E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins. (e3ligasesignal.com)
  • 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)
  • Advancing this inhibitor and studying the functions of this understudied protein is just a taste of what is to come from the Nabet Lab. (fredhutch.org)
  • P27 is a cyclin-dependent kinase inhibitor that negatively regulates cell proliferation. (springeropen.com)
  • P27 is a cyclin-dependent kinase inhibitor (CKI) that controls protein synthesis during the cell cycle. (springeropen.com)
  • Agonist (100 nM 8-OH-DPAT) (D) treatment of freely dividing HN2-5 cells caused stimulation of PKC (Physique 1a) [25,26,27,28,29], which was blocked by the 5-HT1A-R antagonist WAY100635 (WAY) (10 M) but not by an inhibitor of the ERK1/2 kinase MEK (U0126) (U) (10 M) (Physique 1a). (thetechnoant.info)
  • 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)
  • Importantly RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine. (immune-source.com)
  • Probably the most abundant viral transcripts in latency will be the U RNAs, which are selelck kinase inhibitor transcribed by DNA poly merase III and reach copy numbers of as much as two 104 copies per cell even though they aren't vital for transformation. (sodiumchannel-signal.com)
  • In fact, as presented in the current study, Cdc5L phos- phorylation inhibitor CVT-313 and DBNL phosphory- lation inhibitor OTSSP167 were highly cytotoxic in 4T1 breast cancer cells and their IC50 values were 20.1 and 43 nM, respectively. (mdm2-receptor.com)
  • 2010). On the other hand, bortezomib in combination with etoposide (a topoisomerase II inhibitor) produced syn- ergistic effects in PC-3 cell line (Aras and Yerlikaya 2016). (mdm2-receptor.com)
  • Cystatin A (Cys A), a cysteine protease inhibitor, is a precursor of proteins involves in keratinocyte keratinization, and is expressed during the late phase of differentiation of these cells. (bvsalud.org)
  • 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)
  • This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. (novusbio.com)
  • p27 regulates G1 /S transition by abrogating the activity of cyclin/CDK complexes. (umass.edu)
  • The Endosomal Sorting Complexes Required for Transport (ESCRT) machinery mediates the membrane fission step that completes cytokinetic abscission and separates dividing cells. (elifesciences.org)
  • 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)
  • Lundberg, A. S. & Weinberg, R. A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. (nature.com)
  • Tight control of the cell cycle in eukaryotic cells exists to control proliferation, differentiation or apoptosis. (benthamscience.com)
  • However, the underlying mechanisms involved in the induction of genomic instability, genotoxicity, mutations and consequent increased cell proliferation are still a matter of intense research. (benthamscience.com)
  • Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. (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)
  • Sphingolipids are an extensive class of lipids with different functions in the cell, ranging from proliferation to cell death. (frontiersin.org)
  • Drosophila CIAPIN1 homologue is required for follicle cell proliferation and survival. (nih.gov)
  • Survival, growth, and proliferation of malignant cells are affected by changes in both pro-apoptotic and anti-apoptotic signaling pathways. (springeropen.com)
  • The cellular protein-protein interaction network that governs cellular proliferation (cell cycle) is highly complex. (pharmafocusasia.com)
  • Somatostatin (SRIH) inhibits cell proliferation by interacting with five distinct SRIH receptor subtypes (SSTRs) activating several pathways in many tissues. (unife.it)
  • We previously demonstrated that SRIH, by activating Src homology-2-containing protein, inhibits cell proliferation of the human medullary thyroid carcinoma cell line, TT, which expresses all SSTRs. (unife.it)
  • Our data show that SRIH and the selective SSTR2 agonist, BIM-23120, reduce cell proliferation and DNA synthesis as well as induce a delay of the cell cycle in G(2)/M phase. (unife.it)
  • Our data indicate that the subtype 2 receptor-mediated antiproliferative effect of SRIH on TT cell proliferation may be exerted through a decrease in cyclin D1 levels. (unife.it)
  • Natural polyamines, putrescine, spermidine and spermine, play essential roles in the regulation of cell growth and proliferation. (spandidos-publications.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)
  • Functional loss of p16 may lead to uncontrolled cell proliferation 3,4 . (bvsalud.org)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • Once a cell is stopped at a checkpoint due to DNA damage, either the damage is repaired or the cell is induced to perform apoptosis. (wikipedia.org)
  • Differentiation and apoptosis have cell cycle withdraw in common, while cancer and degenerative processes both show altered control of the cell cycle. (benthamscience.com)
  • As a consequence of treatments, the most frequent mechanism of cell death is apoptosis, followed by autophagy. (frontiersin.org)
  • Sphingolipids are remarkably diverse and have crucial roles in maintaining barrier function and fluidity, as well as regulating the cell cycle, cell motility, differentiation, adhesion, and apoptosis ( 1 ). (frontiersin.org)
  • It is expressed in cancer cells during the G2/M phase of the cell cycle and counteracts apoptosis activation during mitosis by interfering with caspase activity [ 6 ]. (springeropen.com)
  • Although purvalanol-induced cell cycle arrest and apoptotic cell death were demonstrated in prostate ( 5 ), breast ( 6 ) and colon cancer cells ( 7 ), the exact molecular mechanism of purvanol-induced apoptosis has not been elucidated yet. (spandidos-publications.com)
  • The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA) leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. (hindawi.com)
  • Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE), and flow cytometry methods. (hindawi.com)
  • Therefore, based on clinical experience as well as cytotoxic activity against multiple human cancer cells, we hypothesized that induction of apoptosis is the underlying mechanism for the treatment of psoriasis. (hindawi.com)
  • Further this build up of poly-ubiquitinated protein is along with a compensatory activation of lysosome-dependent proteins degradation stabilization of p53 the destabilization of cyclin D1 as well as the starting point of apoptosis. (immune-source.com)
  • The process of systemically destroying damaged cell is called apoptosis and is signaled for and controlled by apoptotic proteins. (lumminary.com)
  • Interestingly, it also interacts with antiapoptotic proteins such as Survivin and cFLIP, which regulate the activity of apoptosis protein. (lumminary.com)
  • The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
  • TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (genetex.com)
  • The cyclin-dependent kinase (CDK) inhibitors p21 and p16 inhibit the activity of CDKs, such as CDK4. (medscape.com)
  • Cancers are known to "hijack" certain cellular pathways, such as developmental programs or cell death mechanisms to hide from the body's immune system and continue their unregulated growth. (fredhutch.org)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
  • Cervical cancer cells exhibit an increased requirement of ubiquitin-dependent protein degradation connected with an increased metabolic turnover price and for particular signaling pathways notably HPV E6-targeted degradation of p53 and PDZ proteins. (immune-source.com)
  • RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. (immune-source.com)
  • Our data uncover novel details about the differential contribution of B2 vs four integrins within the composite phenotype of chronic asthma development and contribute towards the understanding of mechanisms by which different cell subsets and molecular pathways participate in the pathophysiology and histopathology of chronic asthma. (sodiumchannel-signal.com)
  • EGCG is especially important and active in many essential cellular pathways including the cell cycle. (lumminary.com)
  • Role in cancer: Cyclin-dependent kinase inhibitors (CKIs) mutants are frequent in human cancers. (wikipedia.org)
  • Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)
  • In recent years, cell cycle regulators have been shown to exhibit roles in both tumor suppression and tumor promotion, particularly cyclin-dependent kinase inhibitors (CKI) p27 kip1 and p21 cip1 14 . (biorxiv.org)
  • Olomoucine, roscovitine and purvalanol are examples of CDK inhibitors (CDKIs) designed and investigated for their apoptotic potential on cancer cells ( 3 ). (spandidos-publications.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)
  • Human cells contain many different cyclins binding to different CDKs. (wikipedia.org)
  • CDKs and cyclins appear and activate at specific cell cycle phases. (wikipedia.org)
  • Further research has demonstrates that Cdks, cyclins and CKIs play essential roles in processes such as transcription, epigenetic regulation, metabolism, stem cell self-renewal, neuronal functions and spermatogenesis. (wikipedia.org)
  • They are expressed in higher numbers in G1 cells to make sure that no S or M CDKs are in the cell. (wikipedia.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)
  • Precise activation and inactivation of CDKs at specific points in the cell cycle are required for orderly cell division. (kegg.jp)
  • Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. (nature.com)
  • Enables cyclin-dependent protein serine/threonine kinase regulator activity. (nih.gov)
  • The active cyclin/CDK complex then phosphorylates proteins, activates them, and sends the cell into the next phase of the cell cycle. (wikipedia.org)
  • N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. (elifesciences.org)
  • In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)
  • Activation of ATR phosphorylates a number of downstream proteins that coordinate the cell cycle checkpoint. (biomedcentral.com)
  • If cell mutations surpass the cell cycle checkpoints during cell cycle regulation, it can result in various types of cancer. (wikipedia.org)
  • They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery. (novusbio.com)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • however, the mechanisms underlying the regulation of cyclin F are poorly understood. (ox.ac.uk)
  • AR protein levels are controlled by both transcriptional regulation [ 4 , 5 ] and post-transcriptional regulation [ 6 ]. (oncotarget.com)
  • Our results suggest that anthracycline-induced cytotoxicity is cell cycle dependent and is mediated, at least in part, by disturbance of the regulation of p34cdc2/cyclin B1 complex, thus leading to G2/M phase arrest. (aspetjournals.org)
  • Another protein, calgranulin A (Cal A), is involved in the regulation of several cell processes, including the cell cycle and cell differentiation. (bvsalud.org)
  • The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
  • 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)
  • The decrease in p27 Kip1 levels is the result of increased proteasome-dependent degradation, mediated and rate-limited by its specific ubiquitin ligase subunits S-phase kinase protein (Skp) 2 and cyclin-dependent kinase subunit (Cks) 1. (haifa.ac.il)
  • We found that AR was ubiquitinated by an E3 ubiquitin ligase, myosin regulatory light chain interacting protein (MYLIP) and then degraded through the ubiquitin-proteasome pathway. (oncotarget.com)
  • Protein degradation by the ubiquitin/proteasome system requires 3 types of enzymes and proceeds through 3 steps. (oncotarget.com)
  • Thus molecules capable of interfering with ubiquitin-dependent protein degradation including Bortezomib show anticancer activity [5]. (immune-source.com)
  • Therefore we hypothesized that stabilization of p53 via preventing its ubiquitin-mediated degradation will have therapeutic potential for cervical cancer and possibly for other cancers wild-type for p53. (immune-source.com)
  • CKIs are vital proteins within the control system that point out whether the process of DNA synthesis, mitosis, and cytokines control one another. (wikipedia.org)
  • Since the cell with damaged DNA is not stopped, the cell eventually moves out of the G1 checkpoint and prepares for DNA synthesis. (wikipedia.org)
  • P27 is inactivated in cancer cells by various mechanisms including impaired synthesis, accelerated degradation, and mislocalization. (springeropen.com)
  • In contrast, Dox treatment was found to induced cyclin B1 accumulation as a result of stimulating its synthesis and inhibiting its degradation. (aspetjournals.org)
  • A fission yeast general translation factor reveals links between protein synthesis and cell cycle controls. (ox.ac.uk)
  • Endoplasmic reticulum (ER) is an essential organelle responsible for protein synthesis, folding, post-translational modification of proteins and protein trafficking in eukaryotes ( 8 ). (spandidos-publications.com)
  • 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)
  • Cyclin A degradation employs preferentially used lysines and a cyclin box function other than Cdk1 binding. (nih.gov)
  • The model starts at mitotic entry initiated by the activities of Cyclin-dependent kinase 1 (CDK1) and Polo-like kinase 1 (PLK1), transitions through Anaphase-promoting complex (APC/C) bound to Cell division cycle protein 20 (CDC20), and ends upon mitotic exit mediated by APC/C bound to CDC20 homolog 1 (CDH1). (pharmafocusasia.com)
  • This is in contrast to control cells where cyclin B 1 appears at the centrosomes in early prophase based on cell cycle-specific localization of CENP-F. Furthermore, cyclin B/Cdk1 kinase activity in early G 2 is aberrantly high in BubR1-depleted cells. (ewha.ac.kr)
  • Purvalanol is a purine-derived CDKI that binds with a high selectivity and competitively to the ATP binding side of CDK1/2 and leads to G2/M cell cycle arrest ( 4 ). (spandidos-publications.com)
  • Our goal was to develop an in silico simulation of human mitosis using published experimental data from human cells by integrating subsets of mechanistic relationships using both quantitative and qualitative data into a single base computational model with enough resolution to approximate outcomes upon perturbation. (pharmafocusasia.com)
  • The role of BubR1 has been established mainly in mitosis as an essential mitotic checkpoint protein although it is expressed throughout the cell cycle. (ewha.ac.kr)
  • hence, cells can leave mitosis in the absence of cyclin degradation or in the absence of the CKI. (ox.ac.uk)
  • CKIs help promote the specific inhibitory signals that contain the cell from entering the S phase. (wikipedia.org)
  • When there is uncontrolled cell growth, it can lead to cancer cells due to the inactivation of the CKIs. (wikipedia.org)
  • Orthologous to several human genes including CCNB1 (cyclin B1). (nih.gov)
  • MiRNAs regulate nearly half of the messenger RNAs in cells, and each miRNA can have up to several hundred target genes. (longlonglife.org)
  • This team science approach has led to recent ground-breaking publications defining roles of new drug targets in Molecular Cell , Cancer Discovery , Genes & Development and Cell Chemical Biology . (fredhutch.org)
  • CNPY2 up-regulated gene expression of AR target genes such as KLK3 gene which encodes the prostate specific antigen (PSA) and promoted cell growth of PC cells. (oncotarget.com)
  • Studies of human genome demonstrate that protein-coding genes only occupy less than 2% of the entire genome [ 1 ]. (ijbs.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Inoculation with a high dose strains of LMP1 transgenic mice vide a powerful tool in mechanistic of EBV caused a B-cell lymphopro- were established that express LMP1 studies on the role of individual viral liferative disorder in these mice, under the control of the immunoglob- genes in cancer. (who.int)
  • The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. (ox.ac.uk)
  • We then studied the effect of Dox on the p34cdc2/cyclin B1 complex because it plays a key role in regulating G2/M phase transition. (aspetjournals.org)
  • Here, we have developed a novel computational model of human mitotic cell cycle, integrating diverse cellular mechanisms, for the purpose of generating new hypotheses and predicting new experiments designed to help understand complex diseases. (pharmafocusasia.com)
  • It includes syntheses and multiple mechanisms of degradations of the mitotic proteins. (pharmafocusasia.com)
  • Protein and gene expression of apoptotic signaling pathway-related proteins such as caspase-3, cytochrome c, and PARP were determined to provide evidence for the mechanisms of action of Tan IIA in the treatment of psoriasis. (hindawi.com)
  • Immunocytochemistry/ Immunofluorescence: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on HeLa cell. (novusbio.com)
  • Western Blot: Cyclin H Antibody (1B8) [H00000902-M01] - CCNH monoclonal antibody (M01), clone 1B8 Analysis of CCNH expression in HeLa. (novusbio.com)
  • WB analysis of HeLa cell lysate using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • To explore a possible role of BubR1 in regulating the G 2 phase of cell cycle, we have employed siRNA-mediated hBubR1 knockdown in HeLa cells. (ewha.ac.kr)
  • Materials and Strategies Cell tradition PJ34 Cervical tumor cell lines HeLa SiHa CaSki and Me personally180 were from American. (immune-source.com)
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)
  • however, purvalanol triggered autophagy, which functions as a cell survival mechanism at early time-points. (spandidos-publications.com)
  • Τheir impact on the apoptotic cell death mechanism requires further elucidation. (spandidos-publications.com)
  • ER alerts a self-protective mechanism that is called ER stress during nutrient deprivation, pathogen infection, alterations in redox status, intraluminal Ca 2+ levels and folding defective protein conditions ( 9 ). (spandidos-publications.com)
  • that is histopathological y very simi- T cel s, B cel s, natural kil er cel s, LMP1 of EBV can transform ro- lar to that caused by hepatitis B vi- macrophages, and dendritic cells, dent fibroblasts and is expressed rus (HBV) in humans, but it does so and this humanized mouse model in most of the human cancers as- through a different mechanism. (who.int)
  • Each Cyclin/CDK complex are specific to the part of the cell cycle phase. (wikipedia.org)
  • This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. (novusbio.com)
  • This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. (docksci.com)
  • Metastasis is a complex, multi-step process that is initiated when cancer cells in the primary tumor acquire invasive properties, including motility and the ability to breakdown the extracellular matrix (ECM) 1 , and is responsible for the majority of cancer-related mortalities 2 . (biorxiv.org)
  • Levels of the B-cyclins Cig2 and Cdc13 are dramatically reduced upon inactivation of Ded1, and this reduction is independent of degradation by the anaphase promoting complex. (ox.ac.uk)
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)
  • BACKGROUND: Loss of the cell-cycle inhibitory protein p27 Kip1 is associated with poor prognosis in colorectal carcinoma. (haifa.ac.il)
  • p38γ and δ promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation. (nature.com)
  • Consistent with this, mRNA and protein levels of the invadopodia key components, cortactin and MT1-MMP, peak at 14 hours post-release. (biorxiv.org)
  • Activated and released IRE1α acts as an RNase to initiate transcription of XBP1 mRNA and it becomes a transcriptional activator for unfolded protein response (UPR) gene targets, such as BiP and calreticulin ( 10 ). (spandidos-publications.com)
  • Thus, we investigated male mouse (m) PRL protein and mRNA expression in spermatozoa at various differentiation stages in the testes. (go.jp)
  • Additionally, circRNAs modulate pre-mRNA alternative splicing and possess protein-coding capacity. (ijbs.com)
  • However, if CKI's mutations don't stop the cell, the Cyclin D is transcribed. (wikipedia.org)
  • Structure-guided point mutations in either CAPN7 MIT domain disrupted IST1 binding in vitro and in cells, and depletion/rescue experiments showed that the CAPN7-IST1 interaction is required for: 1) CAPN7 recruitment to midbodies, 2) efficient abscission, and 3) NoCut checkpoint arrest. (elifesciences.org)
  • In two independent screens we isolated fission yeast mutations with phenotypes suggesting defects in B-cyclin function or expression. (ox.ac.uk)
  • Expression of p63 is almost exclusively restricted to epithelial cells, mutations in this gene are infrequent, and its expression is increased in a variety of solid tumors, particularly those of the head and neck area 12,13 . (bvsalud.org)
  • Cell cycle consists of oscillating changes in protein concentrations and activities within the cell allowing for duplication of the host genome and eventual cell division. (pharmafocusasia.com)
  • The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. (intechopen.com)
  • It moves into the cytoplasm and eventually activates a specific cyclin-dependent kinase (CDK). (wikipedia.org)
  • Cyclin B Export to the Cytoplasm via the Nup62 Subcomplex and Subsequent Rapid Nuclear Import Are Required for the Initiation of Drosophila Male Meiosis. (nih.gov)
  • This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. (genetex.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)
  • Moreover, we determined that during purvalanol-mediated ER stress, autophagic machinery was also activated prior to apoptotic cell death finalization. (spandidos-publications.com)
  • EGCG has also been shown to interact with apoptotic proteins such as Caspase 3, 7 and 8. (lumminary.com)
  • These are small RNAs that do not code for proteins, but will interact with gene transcripts, messenger RNAs (mRNAs), or transcriptional modulators, to control them. (longlonglife.org)
  • Circular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), are ubiquitously expressed in eukaryotic cells during post-transcriptional processes. (ijbs.com)
  • 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)
  • Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. (intechopen.com)
  • Altered responsiveness to co- oup the nucleus accumbens reflect the behavioral approaches that incorporate caine and increased immobility in the forced swim test associated with elevated cAMP response ele- memory of associations between the extinction-like processes may have effi- ment binding protein in nucleus accumbens. (lu.se)
  • In a cell-free system, Dox did not inhibit p34cdc2 kinase activity, indicating that is has no direct effect on the enzyme function. (aspetjournals.org)
  • It is very important and is tightly regulated, accidental runaway cell growth/division leads to cancer, commonly defined as aberrant cell growth. (lumminary.com)
  • Liver-specific pRB loss results in ectopic cell cycle entry and aberrant ploidy. (nature.com)
  • Checkpoint systems allow the accurate execution of each cell-cycle phase. (ox.ac.uk)
  • Cell cycle-dependent cytotoxicity, G2/M phase arrest, and disruption of p34cdc2/cyclin B1 activity induced by doxorubicin in synchronized P388 cells. (aspetjournals.org)
  • Treatment of synchronized cells in early S phase with 1 microM Dox (2 x ID50) for 1 hr induced a marked cell arrest at G2/M phase at 6-12 hr after drug incubation. (aspetjournals.org)
  • In this study, using invadopodia- and cell cycle- fluorescent markers, we show in 2D and 3D cell cultures, as well as in vivo , that breast carcinoma cells assemble invadopodia and invade into the surrounding ECM preferentially during the G1 phase of the cell cycle. (biorxiv.org)
  • Cells synchronized in the G0/G1 phase of the cell cycle degrade at significantly higher levels during the first 20 hours post-synchronization release. (biorxiv.org)
  • As expected, BubR1 depletion leads to degradation of cyclin B 1 in the G 2 phase. (ewha.ac.kr)
  • Intriguingly, cyclin B 1 is prematurely targeted to centrosomes appearing at early G 2 phase in BubR1-depleted cells despite its low levels. (ewha.ac.kr)
  • Our data provide a new insight whereby rapamycin signaling via the Torc1 kinase may exploit the pheromone pathway to arrest cells in the G 1 phase. (researchsquare.com)
  • As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)
  • Through its interactions with other proteins via its BRCT domains, hTopBP1 performs diverse functions [ 1 ]. (biomedcentral.com)
  • In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
  • We show that B-cyclin translation is specifically inhibited upon nitrogen starvation of wild-type cells, when B-cyclin/Cdc2 inactivation is a prerequisite for G(1) arrest and subsequent mating. (ox.ac.uk)
  • Herein, we screened a histone mutant collection and report that one of the mutants, H2B R95A, is strikingly resistant to rapamycin due to a defective cell cycle arrest. (researchsquare.com)
  • Of these mutants, H2B R95A displayed striking resistance to rapamycin, which correlated with an inability to undergo cell cycle arrest. (researchsquare.com)
  • Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)
  • The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
  • Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. (docksci.com)
  • Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)
  • hTopBP1 and hMYH were involved in ATR-mediated Chk1 activation, moreover, both of them were associated with ATR and hRad9 which known as checkpoint-involved proteins. (biomedcentral.com)
  • Therefore, we suggest that the interaction between hMYH and hTopBP1 is crucial for activation of the ATR-mediated cell cycle checkpoint. (biomedcentral.com)
  • Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.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)
  • To do this, he wondered if he could "hijack the cell's garbage disposal machinery" to trick cancer cells into degrading the oncogenic proteins that made them cancer cells to begin with, Dr. Nabet explains. (fredhutch.org)
  • PROTACs are bifunctional molecules that recruit a protein, such as a cancer-driving protein with one end, while the other end recruits the cell's own garbage disposal machinery to degrade the targeted protein. (fredhutch.org)
  • dTAG molecules bind to this universal tag instead of the protein directly, while also recruiting the cell's garbage disposal machinery to degrade the tagged protein. (fredhutch.org)
  • Lacking proteosomal function on aggregates of unfolded proteins, ER stress may induce autophagic machinery. (spandidos-publications.com)
  • Also, the INK4 proteins help stop the G1-CDK activity when they encounter anti-proliferative signals within the environment. (wikipedia.org)
  • Nabet is focused on developing proximity-based therapeutics that redirect the cell's own processes for controlling protein levels and activity. (fredhutch.org)
  • This dynamic oscillatory behavior is regulated by the activity of ECM receptor integrin β1, which determines the length of time a cell spends in each state. (biorxiv.org)
  • 2015). In contrast, the combination of bortezomib with docetaxel or with irinotecan does not appear to have significant antitumor activity against metastatic head and neck squamous cell carcinoma or colorectal cancer, respectively (Kozuch et al. (mdm2-receptor.com)
  • Temperature-Induced uncoupling of cell cycle regulators. (nih.gov)
  • The antiviral dsRNA-binding proteins, NF90/NF110, act as key regulators in circRNA biogenesis. (ijbs.com)
  • Immunohistochemistry-Paraffin: Cyclin H Antibody (1B8) [H00000902-M01] - Analysis of monoclonal antibody to CCNH on formalin-fixed paraffin-embedded human testis. (novusbio.com)
  • Sandwich ELISA: Cyclin H Antibody (1B8) [H00000902-M01] - Detection limit for recombinant GST tagged CCNH is approximately 1ng/ml as a capture antibody. (novusbio.com)
  • Quality control test: Antibody Reactive Against Recombinant Protein. (novusbio.com)
  • Antibody reactivity against cell lysate and recombinant protein for WB. (novusbio.com)
  • IHC-P analysis of human tonsil tissue using GTX33611 Cyclin D1 antibody [RM241]. (genetex.com)
  • There are currently no references for Cyclin D1 antibody [RM241] (GTX33611) . (genetex.com)
  • In spite of the effectivity in hematolog- ical cancers and in many cancer cell lines, bortezomib does not appear to produce significant clinical results in solid malignancies when it is used alone (Chao and Wang 2016). (mdm2-receptor.com)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (novusbio.com)
  • We previously demonstrated that invasive cells oscillate between two distinct states, termed the Invadopodia state and the Migration state 10 . (biorxiv.org)
  • Together, our results indicate that hBubR1 depletion triggers premature centrosomal localization of cyclin B 1 probably leading to premature mitotic entry. (ewha.ac.kr)
  • In breast cancer, the cellular structures responsible for ECM degradation are invadopodia. (biorxiv.org)
  • Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)
  • In addition, to allow manipulating the levels of endogenous proteins at will, we introduce a novel approach to render already existing GFP (trap) lines amenable to auxin-dependent degradation by simple ectopic expression of a degradation cassette using human cells and zebrafish as a proofs of principle. (cam.ac.uk)
  • The androgen receptor (AR) is a ligand-dependent transcription factor that promotes prostate cancer (PC) cell growth through control of target gene expression. (oncotarget.com)
  • Here, we hypothesized that specific histone residue(s) might be involved in facilitating gene expression such that cells mount a response to rapamycin. (researchsquare.com)
  • Notably, circRNAs display cell-type, tissue-type and developmental-stage specific expression patterns in eukaryotic transcriptome, which reveals their significant regulatory functions in gene expression. (ijbs.com)
  • Each protein provided significant additional prognostic information to that given by disease stage, tumor grade, or p27 Kip1 expression. (haifa.ac.il)
  • The expression of both proteins was variable among different solid tumors including UC. (springeropen.com)
  • Immunopositivity (number of positive cases) and expression score (percentage of positive urothelial cells) were evaluated. (springeropen.com)
  • The expression of the STE5 gene and its encoded scaffold protein Ste5, required for the sequential activation of the MAPKs of the pheromone pathway, is greatly reduced in the H2B R95A mutant. (researchsquare.com)
  • Quantitative RT-PCR and in situ hybridization detected the expression of PRL not only in Leydig cells but also in germ cells, in particular in spermatogonia. (go.jp)
  • During the early stage of cerebral I/R injury, significantly-swollen mitochondria decrease adenosine triphosphate (ATP) and produce excessive reactive oxygen species (ROS) and oxidative stress, finally resulting in cell death [ 6 ]. (biomedcentral.com)