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  • functions
  • In addition to playing a role in ATM activation, NBS1 also functions downstream of ATM in regulating the intra-S-phase checkpoint ( 9 ⇓ - 11 ). (pnas.org)
  • However, overexpression of ATR complements the radioresistant DNA synthesis defect of cells lacking ATM, demonstrating that these two kinases have overlapping functions in vivo. (asm.org)
  • Some types of cells, such as nerve and heart muscle cells, become post-mitotic when they reach maturity (i.e., when they are terminally differentiated) but continue to perform their main functions for the rest of the organism's life. (wikibooks.org)
  • Our understanding of the important functions of p38 MAPK in the process of differentiation and cell death has grown considerably in the recent years and is now relatively established. (ijbs.com)
  • However disruption of the p38α gene results in embryonic death because of placental defects demonstrating that some functions cannot be compensated by other family members[ 3 - 6 ]. (ijbs.com)
  • Although STAU2 functions have been reported in neuronal cells, its role in dividing cells remains deeply uncharacterized. (biomedcentral.com)
  • HRAD9 also functions as a cell death mediator. (aacrjournals.org)
  • These findings suggested that HHUS1 and HHUS1B have related but not identical functions in cell cycle checkpoint control and perhaps other as of yet undefined cellular processes. (aacrjournals.org)
  • We are using genetic, molecular and cell biological analyses in both the fruitfly, Drosophila melanogaster, and in the mouse, to address some specific questions such as when, why and how cells acquire their morphology to carry out their functions. (stanford.edu)
  • vivo
  • We noticed that in contrast to robust MDC1 foci formation after DNA damage, the formation of NBS1 foci in cells expressing exogenous NBS1 was not readily detectable ( Fig. 1 A ). We speculated that this failure of proper NBS1 localization could be due to the limited expression of an endogenous protein or proteins required for NBS1 foci formation in vivo . (pnas.org)
  • Serines 317 and 345 were identified as sites of phosphorylation in vivo, and ATR (the ATM- and Rad3-related protein kinase) phosphorylated both of these sites in vitro. (asm.org)
  • Moreover, this phenomenon could be induced in vivo because it can be achieved without introducing foreign genes. (developmentsrilanka.com)
  • Bimolecular-fluorescence complementation assay to monitor kinase-substrate interactions in vivo. (uni-hamburg.de)
  • Chk1
  • Here we show that human cells lacking Chk1 exhibit defects in both the ionizing radiation (IR)-induced S and G 2 checkpoints. (pnas.org)
  • In addition, loss of Chk1 resulted in the accumulation of a hypophosphorylated form of the Cdc25A protein phosphatase, and Chk1-deficient cells failed to degrade Cdc25A after IR. (pnas.org)
  • The IR-induced S and G 2 checkpoints were partially restored in Chk1-deficient cells when Cdc25A accumulation was interfered with. (pnas.org)
  • Mouse embryos and conditional embryonic stem cell lines lacking Chk1 exhibit defective checkpoint responses to replication blocks and DNA-damaging agents establishing a checkpoint function for Chk1 in mice ( 8 , 9 ). (pnas.org)
  • Evidence that Chk1 contributes to G 2 checkpoint control in human cells comes from studies showing that agents such as UCN-01 and SB-218078, which are potent inhibitors of Chk1, abrogate G 2 checkpoint function in human cells ( 10-12 ). (pnas.org)
  • However, it is clear that Chk1 is not the only kinase targeted by UCN-01 (see below). (pnas.org)
  • Although Chk1 is conserved throughout evolution, the signals that Chk1 responds to have diverged among eukaryotic organisms. (pnas.org)
  • In Xe and humans, Chk1 is phosphorylated and activated by ATR (ATM and Rad3-related protein kinase), and the ATR/Chk1 pathway responds to agents that impair DNA replication, either directly (hydroxyurea, aphidicolin) or indirectly (UV irradiation) ( 8 , 13 , 14 ). (pnas.org)
  • In this study, we investigated the contribution made by human Chk1 to the cell division cycle both in the absence and presence of checkpoint activation. (pnas.org)
  • We report that cells deficient in human Chk1 exhibit radio-resistant DNA synthesis and do not delay in G 2 after IR treatment. (pnas.org)
  • We provide evidence that Chk1 directly regulates Cdc25A throughout an unperturbed cell cycle, and that the integrity of the Chk1/Cdc25A regulatory pathway is essential for cells to respond appropriately to ionizing radiation. (pnas.org)
  • Chk1 is an evolutionarily conserved protein kinase that regulates cell cycle progression in response to checkpoint activation. (asm.org)
  • The phosphorylated form of Chk1 possessed higher intrinsic protein kinase activity and eluted more quickly on gel filtration columns. (asm.org)
  • In addition, this study implicates ATR as a direct upstream activator of Chk1 in human cells. (asm.org)
  • interactions
  • Background: The chromatin immunoprecipitation (ChIP) assay is a powerful and versatile technique used for probing protein-DNA interactions within the natural chromatin context of the cell (1,2). (cellsignal.com)
  • Interactions between death-promoting and death-suppressing Bcl-2 family members has led to a rheostat model in which the ratio of pro-apoptotic and anti-apoptotic proteins controls cell fate (4). (cellsignal.com)
  • The complex inflammasome structure is built via domain interactions among the protein components. (cellsignal.com)
  • From diverse functional genomics data, we show that phosphoproteins have a higher number of interactions than an average protein and interact with each other more than with a random protein. (pnas.org)
  • regulates
  • Activated caspase-1 induces secretion of proinflammatory cytokines IL-1β and -18, but also regulates metabolic enzyme expression, phagosome maturation, vasodilation, and pyroptosis, an inflammatory programmed cell death. (cellsignal.com)
  • mitotic spindle
  • First, condensed sister chromatids attach to the mitotic spindle at the center of the cell. (biologyreference.com)
  • The mitotic spindle, a fanlike array of microtubules, mediates the separation of all sister chromatid pairs as the chromatids, now called chromosomes, synchronously move to opposite poles of the cell. (biologyreference.com)
  • Initiation of DNA synthesis, assembly and integrity of the mitotic spindle, and chromosome attachment to the mitotic spindle are all regulated by checkpoints. (biologyreference.com)
  • Despite their aberrant morphology the cells terminally arrested just like the control cells on the metaphase-anaphase changeover as judged by the current presence of a brief mitotic spindle (Fig.?1B) and an individual septin band (Fig.?1C) and in addition by their 2C DNA articles (Fig.?1D) and their undivided nuclei. (bioinbrief.com)
  • MRE11
  • The product of the Nijmegen breakage syndrome gene (NBS1) plays crucial roles in DNA damage response through its association with many proteins, including MRE11 and RAD50. (pnas.org)
  • The evolutionarily conserved MRE11/RAD50/NBS1 (MRN) complex plays important roles in cell cycle checkpoint signaling and DNA repair. (pnas.org)
  • In fact, without CtIP or Mre11 cells are sensitive to topoisomerase poisons such as camptothecin (CPT) since they are unable to deal with the topoisomerase covalently attached to DNA. (openwetware.org)
  • responses
  • Cell lines derived from patients lacking ATM are radiosensitive and exhibit defects in checkpoint responses to ionizing radiation (IR), including p53-dependent G 1 cell cycle arrest and p53-independent S and G 2 cell cycle arrests ( 31 ). (asm.org)
  • Checkpoint responses to UV light and base-damaging agents are normal in cells lacking ATM . (asm.org)
  • 3 ] Genomic lesions can be recognized and labeled by recruitment of sensor proteins, which activates a complex network of cellular responses known as DNA damage response (DDR) and mobilizes DNA repair machinery in order to maintain genomic integrity. (jcmtjournal.com)
  • While a broader, systems-level analysis of biological responses to infection is urgently needed, recent advances on proteomic studies have yielded new insights on the impact of infection on the host cell. (frontiersin.org)
  • These subunits induce intracellular responses that can be highly polarized when a cell experiences a gradient of chemoattractant. (jove.com)
  • endogenous
  • 2 ] DSB can be induced by environmental exposure such as ultraviolet (UV) or ionizing radiation (IR), as well as by endogenous agents like reactive oxygen species generated by cell metabolism. (jcmtjournal.com)
  • discovery of endogenous inhibitors of Src kinases. (stanford.edu)
  • embryonic
  • Unlike ATM , deletion of ATR in mice results in an embryonic lethal phenotype indicating that ATR is an essential gene ( 6 , 17 ). (asm.org)
  • signals
  • Another feature that distinguishes these two kinases is their sensitivity to different types of checkpoint signals. (asm.org)
  • 3D: Cells communicate by generating, transmitting and receiving chemical signals. (prezi.com)
  • SirT1 deficiency deregulates the expression of IGF-1 binding protein-1 and attenuates the effect of IGF-1 signals, including estrogen-stimulated local IGF-1 signaling for the onset of ductal morphogenesis. (biomedcentral.com)
  • The activation of a naive T-Cell requires two signals: ligation of the TCR (T-Cell Receptor) with the MHC (Major Histocompatibility Complex)/peptide complex on the APC (Antigen Presenting Cell). (qiagen.com)
  • activation
  • Disruption of the MDC1-NBS1 interaction results in failure of NBS1 accumulation at DNA double-strand breaks and impairment of intra-S checkpoint activation. (pnas.org)
  • Cells derived from NBS and ATLD patients are hypersensitive to radiation and display impaired intra-S-phase checkpoint activation ( 1 ⇓ - 3 ), supporting critical roles of this complex in DNA damage response. (pnas.org)
  • Upon activation, checkpoints interface with cyclin-Cdk complexes to block cell cycle progression or alternatively to induce cell death. (asm.org)
  • 7 - 9 ] The inactive NF-κB is present in the cytoplasm in most cell types and it can be activated by a variety of extra-cellular stimuli such as pro-inflammatory cytokines, bacterial lipopolysaccharides, and viral RNA and DNA, via the activation of membrane and cytosolic receptors. (jcmtjournal.com)
  • These events are coordinated with global changes in transcriptional patterns and DNA repair activation to ensure that the cell cycle progresses and DNA replication resumes once the damage is repaired. (biomedcentral.com)
  • However, T1989 is not evolutionarily conserved and there are conflicting data about how important its phosphorylation is to the ATR activation process. (developmentsrilanka.com)
  • Pubmed ID: 15563608 Activation of G-protein-coupled chemoattractant receptors triggers dissociation of Galpha and Gbetagamma subunits. (jove.com)
  • Here, we quantitatively measure temporal and spatial changes of receptor occupancy, G-protein activation by FRET imaging, and PIP3 levels by monitoring the dynamics of PH(Crac)-GFP translocation in single living cells in response to different chemoattractant fields. (jove.com)
  • dependent
  • Besides regulating ATM-dependent phosphorylation of SMC proteins ( 12 , 13 ), the mechanism by which NBS1 participates in this intra-S-phase checkpoint remains elusive. (pnas.org)
  • Transition between stages is triggered by cyclin-dependent kinases (CDK). (biologyreference.com)
  • Many interacting factors, not directly implicated in FA pathologies, have been identified, including Bloom syndrome RecQ helicase-like, DNA ligase 4, DNA-dependent protein kinase, both subunits of the KU heterodimer (KU70 and KU80), and FANCD2/FANCI-associated nuclease 1 (FAN1). (plantcell.org)
  • This step is associated with the recruitment of many other factors to the origin by the S-phase promoting kinases CDK and Dbf4-dependent Cdc7 Kinase (DDK) ( Labib 2010 ). (g3journal.org)
  • cAMP (Cyclic 3, 5-Adenosine Monophosphate)-dependent Protein Kinase, commonly known as PKA (Protein Kinase-A), is a second messenger-dependent enzyme that has been implicated in a wide range of. (qiagen.com)
  • tumor
  • One study has reported that the p53 tumor suppressor protein competes with Sp1 for binding to the POLD1 promoter. (wikipedia.org)
  • Methodology/Principal Findings: In this study, we report that the expression of Sphingosine Kinase 1 (SphK1) protein was preferentially elevated in MPM tumor tissues (49 epithelioid and 13 sarcomatoid) compared to normal tissue (n = 13). (docplayer.net)
  • The abundance of HRAD9B RNA, as judged by quantitative reverse transcription-PCR, is very low in most testicular tumors, particularly those of germ cell origin, i.e. , seminomas, relative to normal testis control, nonseminomas, or Leydig tumor cells. (aacrjournals.org)
  • The long-term goal is to identify and characterize the molecular and physiological changes induced by the tumor microenvironment that influence the malignant progression of transformed cells. (stanford.edu)
  • genomic
  • Meiosis is a specialized cell division that ensures reduction of genomic content by half and DNA exchange between homologous chromosomes via crossovers (COs) prior to gamete formation. (plantcell.org)
  • Groups of genes that are frequently observed in each other's genomic neighborhood. (string-db.org)
  • In the current review we discuss a subset of these proteins involved in the direct maintenance of genomic stability, an important cellular process in the conservation of cellular viability and prevention of malignant transformation. (biomedcentral.com)
  • amino
  • These proteins are encoded by separate genes and are approximately 60% identical at the amino acid level. (ijbs.com)
  • In silico analyses of the amino acid sequence of Sj -RIOK-2 revealed typical features of this class of kinases including a winged helix (wHTH) domain and a RIO kinase domain. (biomedcentral.com)
  • The Mrad9B protein is 398 amino acids long and is 50% similar and 35% identical to its paralogue. (aacrjournals.org)
  • Morphogenesis
  • Exogenous estrogen reversed the increased basal level of IGF-1 binding protein-1 expression in SirT1 ko/ko mammary tissues, but not that of IκBα expression, suggesting that increased levels of estrogen enhanced the production of local IGF-1 and rescued ductal morphogenesis. (biomedcentral.com)
  • Trichome morphogenesis - a cell cycle perspective. (uni-hamburg.de)
  • target genes
  • We aim to identify and characterize p53 target genes, and under p53 function through in-depth structure-function studies. (stanford.edu)