• Well-characterized cell cycle substrates of SCF complexes include: cyclin family proteins: Cyclin D, Cyclin E transcriptional regulators: Myc, E2f1, p130 cyclin-dependent kinase inhibitors (CKIs): p27Kip1, p21, Wee1 centriole proteins: Cep250, Ninein There are approximately seventy human FBPs, several of which are involved in cell cycle control as a component of SCF complexes. (wikipedia.org)
  • In addition, phosphorylated ERK1/2 and p38, key members of mitogen-activated protein kinase (MAPK) family regulating BCa tumorigenesis, were strongly decreased. (spandidos-publications.com)
  • 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)
  • 4, Cell cycle regulators mediate progression through the cell cycle {e.g., cyctin and cyclin-dependent kinase). (ctsqena.com)
  • Inhibitor of checkpoint kinase CHK1 was identified as a top screen hit. (nature.com)
  • Many cancers show aberrant signalling via the insulin-like growth factor (IGF) axis, activating type 1 IGF receptors (IGF-1Rs) and variant insulin receptors (INSRs) to signal via phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) and mitogen-activated protein kinase kinase-extracellular signal-regulated kinases (MEK-ERK) [ 1 ]. (nature.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)
  • A vast amount of research exists on the possible molecular mechanisms through which vitamin D affects cancer cell proliferation, cancer progression, angiogenesis, and inflammation. (mdpi.com)
  • Taken together, our results suggested that decreased LAPTM5 inhibited proliferation and viability, as well as induced G0/G1 cell cycle arrest possibly via deactivation of ERK1/2 and p38 in BCa cells. (spandidos-publications.com)
  • Furthermore, previous studies suggested that knockdown of LAPTM4B , another important subtype of the LAPTM family inhibited proliferation of hepatocellular carcinoma ( 11 ), prostate ( 12 ) and breast cancer cells ( 13 ). (spandidos-publications.com)
  • The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2′-deoxyuridine assay, propidium iodide (PI) staining, annexin V-fluorescein isothiocyanate/PI staining, and transwell assay were employed to test the proliferation, apoptosis, migration ability, and invasiveness of COAD cells. (hindawi.com)
  • Upregulating the level of miR-323a-3p impaired the proliferation, migration, and invasion of COAD cells and promoted apoptosis, whereas supplementing NEK6 alleviated the damage of the proliferation, migration, and invasion of COAD cells caused by miR-323a-3p and inhibited miR-323a-3p-induced apoptosis. (hindawi.com)
  • These findings indicate that miR-323a-3p regulates the proliferation, migration, invasion, and apoptosis of COAD cells by targeting NEK6. (hindawi.com)
  • Further, high NEK2 expression promoted proliferation, colony formation, migration and invasion of HCC cell lines. (oncotarget.com)
  • Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
  • Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 muM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. (proteopedia.org)
  • Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • In contrast, no significant alteration of apoptosis in the BCa cells with downregulated LAPTM5 was noticed. (spandidos-publications.com)
  • If cells containing damaged DNA were to divide, the errors would be transmitted to daughter cells, generating genomic instability and resulting in tumorigenesis or apoptosis . (tocris.com)
  • 3. B cells that would normally undergo apoptosis during somatic hypermutation in the lymph node germinal center accumulate, leading to lymphoma. (ctsqena.com)
  • In some p53 mutants, induction of cell cycle arrest, but not apoptosis was found to be associated with a lack of induction of PIG3 expression ( 2 ). (ijbs.com)
  • Silencing of the transcription factor hCAS/CSE1L, which regulated PIG3 expression, led to decreased PIG3 transcription and concurrently decreased apoptosis ( 3 ). (ijbs.com)
  • Additionally, PIG3 mediates cancer cell death through the GPx3 pathway, and knocking down PIG3 or blocking the interaction between PIG3 and GPx3 would abolish the increase in ROS and apoptosis ( 5 ). (ijbs.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)
  • These checkpoints may stop the cell cycle after DNA damage, loss of DNA replication or disruption of the mitotic spindle, in order for repair processes to take place. (tocris.com)
  • It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death. (tocris.com)
  • Recombination between homologous sequences is a fundamentally important process both in meiosis and in mitotic cells. (brandeis.edu)
  • To this end we have expressed the site-specific HO endonuclease in meiotic cells so that we can compare recombination events at the same loci where we have used HO to stimulate recombination in mitotic cells. (brandeis.edu)
  • The activity of NEK6 plays important roles in mitotic spindle kinetochore fiber formation, metaphase-anaphase transition, cytokinesis, and checkpoint regulation [ 3 , 4 ]. (hindawi.com)
  • Members of the dynein and kinesin superfamilies play critical roles in transporting biological payloads (such as proteins, organelles, and vesicles) along microtubule pathways, cause the beating of flagella and cilia, and act within the mitotic and meiotic spindles to segregate replicated chromosomes to progeny cells. (bvsalud.org)
  • 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)
  • PIG3 knockdown led to an abnormal DNA damage response, including decreased IR-induced phosphorylation of H2AX, Chk1, Chk2 and Kap-1 as well as a prolonged G2-M arrest and aberrant mitotic progression. (ijbs.com)
  • miRNAs expressed in a wide variety of human cancers can regulate posttranscriptional gene expression by binding to the 3′ untranslated region of the target mRNAs and act as oncogenes or tumor suppressors to regulate cell signaling pathways, affecting tumorigenesis and tumor progression [ 17 ]. (hindawi.com)
  • ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
  • PIG3 knockdown can suppress intra-S phase and G2/M checkpoints ( 8 ). (ijbs.com)
  • 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)
  • The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
  • Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
  • Primary cilia are microtubule-based organelles that are widespread on the cell surface and play a key role in tissue development and homeostasis by sensing and transducing various signaling pathways. (bvsalud.org)
  • Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
  • 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)
  • In COAD cells, NEK6 was highly expressed, whereas miR-323a-3p was expressed at low levels and negatively regulated NEK6. (hindawi.com)
  • In addition cells have evolved a damage-sensing checkpoint system whereby the cells delay entry into mitosis until the break has been repaired. (brandeis.edu)
  • For a cell to progress through the cycle and replicate, it must pass through checkpoints between phases to ensure that DNA is replicated correctly and that chromosomes segregate. (tocris.com)
  • In the mitosis, the chromosomes are aligned and the two sister chromatids are separated, each becoming the genetic material of the daughter cells. (androbose.in)
  • A human cell at this point has 46 chromosomes (and 92 chromatids). (androbose.in)
  • The eukaryotic cell cycle is regulated through the synthesis, degradation, binding interactions, post-translational modifications of regulatory proteins. (wikipedia.org)
  • Along with the anaphase-promoting complex, SCF has important roles in the ubiquitination of proteins involved in the cell cycle. (wikipedia.org)
  • Of these regulatory proteins, two ubiquitin ligases are crucial for progression through cell cycle checkpoints. (wikipedia.org)
  • In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. (tocris.com)
  • Using lysate-based single-molecule motility assays and live-cell imaging in primary neurons, we show that JNK-interacting proteins 3 (JIP3) and 4 (JIP4) are activating adaptors for dynein that are regulated on autophagosomes and lysosomes by the small GTPases ARF6 and RAB10. (bvsalud.org)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • We have been fascinated by the process of yeast mating-type gene switching, in which cells replace about 700 bp of Ya or Y-specific DNA sequences at the MAT locus by recombining with one of two donor loci, called HMLDescription: image3 and HMRa. (brandeis.edu)
  • Changes in methylation of this gene could impact progression of gametogenesis or embryogenesis. (github.io)
  • Methyalation of this gene could promote homeostasis by regulating gonad development processes. (github.io)
  • Increased expression of this gene in Artemia sinica can suppress cell division and macromolecule synthesis (Jiang 2011), so methylation may be regulating gonad development. (github.io)
  • The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. (affbiotech.com)
  • Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • Moreover, cell cycle arrest at G0/G1 phase was triggered by decreased LAPTM5 as well, which could lead to delayed BCa cell growth. (spandidos-publications.com)
  • Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
  • 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)
  • Investigating the mechanism of synthetic lethality, we reveal that CHK1 inhibition in IGF-1R depleted or inhibited cells further downregulated RRM2, reduced dNTP supply and profoundly delayed replication fork progression. (nature.com)
  • transport is driven by the microtubule motor protein cytoplasmic dynein, with motor activity regulated by a sequential series of adaptors. (bvsalud.org)
  • Co-inhibition of IGF and CHK1 caused synergistic suppression of cell viability, cell survival and tumour growth in 2D cell culture, 3D spheroid cultures and in vivo. (nature.com)
  • Our transcriptome analysis revealed in bladder cancer (BCa) tissues a significant induction of lysosomal-associated multispanning membrane protein 5 (LAPTM5), a lysosomal membrane protein preferentially expressing in immune cells and hematopoietic cells. (spandidos-publications.com)
  • LAPMT5 is a lysosomal membrane protein preferentially expressed in immune cells ( 5 , 6 ) and hematopoietic cells ( 7 ), having a close interaction with the Nedd4 ( 8 ), a member of the E3 ubiquitin ligases family ( 8 ). (spandidos-publications.com)
  • Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells. (uc.edu)
  • The centrosomes which help in the arrangement of microtubules to form spindle fibers, move to the opposite poles of the cell. (androbose.in)
  • Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)
  • 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)
  • Overall, genes are mainly involved in developmental progression and regulation. (github.io)
  • Moreover, some studies demonstrated that LAPTM5 was highly expressed in malignant B lymphomas and involved in B cell malignancies ( 10 ), involving in negative regulation of cell surface T and B cell receptor by promoting lysosome degradation ( 6 ). (spandidos-publications.com)
  • We have shown that this regulation involves the action of a small Recombination Enhancer (RE) sequence that enables a donor on the left chromosome arm to recombine preferentially in MATa cells. (brandeis.edu)
  • As main findings, 23 miRNAs were already identified as being involved in genetic regulation of PCa cell response to RT. (frontiersin.org)
  • During EMT, cells will undergo transformation from epithelial phenotype to mesenchymal phenotype ( 14 ) and many characteristics of cells will change including loss of cell-cell adhesion and acquisition of aggressive and metastatic ability ( 15 ). (spandidos-publications.com)
  • RON-augmented cholesterol biosynthesis in breast cancer metastatic progression and recurrence. (uc.edu)
  • The RAS-regulated RAF-MEK1/2-ERK1/2 signalling pathway is frequently de-regulated in human cancer. (babraham.ac.uk)
  • CDKs regulate the cell's progression through the phases of the cell cycle by modulating the activity of key substrates. (kegg.jp)
  • Specifically, SCF has been shown to regulate centriole splitting from late telophase to the G1/S transition. (wikipedia.org)
  • In recent years, epithelial-mesenchymal transition (EMT) has been suggested to play a key role in the process of embryonic development, differentiation of tissues and organs, chronic inflammation and fibrosis, as well as cancer progression ( 14 ). (spandidos-publications.com)
  • Finally, the appearance degrees of both types of the EIAV receptor had been considerably regulated by an infection with this trojan. (angiogenesis-blog.com)
  • Transportation of LAPTM5 from Golgi to lysosome could be inhibited by deficiency of Nedd4, a key member of E3 ubiquitin ligase family overexpressing in invasive BCa and promoting its progression. (spandidos-publications.com)
  • We conducted a systematic review of the literature on the effects of vitamin D on ovarian cancer cell. (mdpi.com)
  • Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. (tocris.com)
  • The activity of NEK6 is enhanced in several cancer cells, including colon adenocarcinoma (COAD) cells. (hindawi.com)
  • One of the treatments applied in cancer is radiotherapy (RT), a therapeutic modality that uses ionizing radiation to induce damage in unwanted cells. (frontiersin.org)
  • A. Cancer formation is initiated by damage to DNA of stem cells. (ctsqena.com)
  • Aiming to exploit this effect in therapy we performed a compound screen in five breast cancer cell lines with IGF neutralising antibody xentuzumab. (nature.com)
  • First, given evidence that IGFs regulate the response to IR, we also found evidence that IGF-1R depletion induced endogenous DNA lesions marked by γH2AX foci in prostate cancer cells [ 10 ]. (nature.com)
  • Analysis of the changes of migration and invasion, showed significant reduced LAPTM5 suppressed cell metastasis. (spandidos-publications.com)
  • As opposed to almost every other lentiviruses, such as for example human immunodeficiency trojan (HIV)-1, simian immunodeficiency trojan (SIV) and feline immunodeficiency trojan (FIV), which need co-receptors for effective an infection, EIAV seems to depend just on an operating ELR1 for the invasion of focus on cells. (angiogenesis-blog.com)
  • Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)
  • Using synchronized cells undergoing recombination that is initiated at a specific site on a chromosome by an inducible endonuclease, we use physical monitoring techniques (Southern blots, PCR analysis) to follow the sequence of molecular events that occur in real time. (brandeis.edu)
  • In the present study, the potential mechanism of PIG3 participation in the DNA damage response induced by ionizing radiation (IR) was investigated in multiple cell lines with depleted expression of PIG3 transiently or stably by the small interference RNA and lentivirus-mediated shRNA expression strategies. (ijbs.com)
  • However, a compensatory feedback of increased mRNA expression of DNA-PKcs was formed in PIG3-depleted cells after a few passages or cell cycles of subculture, which led the recovery of the DNA-PKcs protein level and the consequent recovered efficiency of the DNA damage response. (ijbs.com)
  • In developing this coculture system, we needed to add PFC neurons in sufficient number to restore glutamate input to 1-Methylinosine NAc neurons while at the same time maintaining a cell density sufficiently low to allow image analysis of single neurons. (bakingandbakingscience.com)
  • To achieve this, preliminary studies were conducted in which we plated different ratios of PFC neurons (fluorescent cells) to NAc neurons (nonfluorescent cells), as determined by cell counting before plating, and investigated the cells after 2 weeks (and supplemental Figs. 2= 17C24, Dunn's test, * 0.05 compared with control group, SCH group, and SCH + SKF group). (bakingandbakingscience.com)
  • Cells like neurons usually get differentiated and perform their functions. (androbose.in)
  • 2020). Unconventional myosins were also found to be important for embryonic development in urchins, specifically to regulate the onset of blastulation and gastrulation stages (Sirotkin 2000). (github.io)
  • Some cells do not undergo cell division, rather they enter the G0 phase either permanently or temporarily wherein they do not divide and remain either quiescent or senescent. (androbose.in)
  • The interphase is a preparatory phase, wherein the cells prepare themselves for the upcoming nuclear and cytoplasmic division. (androbose.in)
  • The cytoplasmic organelles are pushed to the periphery of the cell. (androbose.in)
  • 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)
  • The main goal of RT consists in delivering a precise dose of radiation in a target volume, such as tumor, promoting the tumor cells eradication with as minimal damage as possible in surrounding normal tissues ( 13 ). (frontiersin.org)
  • These changes can be inherited and are, therefore, found in every cell, but more often, they are somatically acquired and restricted to tumor cells. (medscape.com)
  • p53 and its transcriptional targets play an important role in both G1 and G2 checkpoints. (kegg.jp)
  • consequently cells have evolved a variety of mechanisms to repair double-strand breaks (DSBs). (brandeis.edu)
  • The method described here can be used in the future to study the microtubule cytoskeleton in (thick) polarized cells such as intestinal epithelial cells. (bvsalud.org)
  • Conclusions Targeting subdominant T cell responses with lower avidity against pMHC affinity neoepitopes showed potential for improving PD-1 immunotherapy. (bmj.com)
  • B. DNA mutations eventually disrupt key regulatory systems, allowing for tumor promotion (growth) and progression (spread). (ctsqena.com)