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  • protein
  • Furthermore, while E2F4, E2F5 and p130(RBL2/RB2) are the major E2F and pocket protein mRNAs in actively proliferating ES cells, expression levels of E2F5, E2F6, and p105(RB1) are most strongly elevated during cell cycle arrest in cells responding to DNA damage. (umassmed.edu)
  • This response may alter the E2F/pocket protein combinations that control E2F dependent genes and block H4 gene expression by inhibiting histone-specific transcription factors and processing of histone gene transcripts, as well as by destabilizing histone mRNAs. (umassmed.edu)
  • At a molecular level, NONO bound to the p16-Ink4A cell cycle checkpoint gene and potentiated its circadian activation in a PER protein-dependent fashion. (pnas.org)
  • In individual cells, the circadian clock mechanism consists of oscillating feedback loops of transcription of "core" oscillator genes and posttranslational modifications of their protein products that regulate protein stability, activity, and/or localization. (pnas.org)
  • These authors showed that Notch-1 N IC transforms MCF-10 cell and protects transformed cells from p53-mediated induction of proapoptotic protein NOXA. (aacrjournals.org)
  • cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein. (springer.com)
  • It affects a plethora of cellular processes including protein trafficking, stability and signalling and is therefore important for all cell types, and organisms from yeast to humans. (sheffield.ac.uk)
  • The plastid signal was originally defined as a pathway that informs the nucleus of the chloroplast status and results in the modulation of expression of nuclear-encoded plastid protein genes. (frontiersin.org)
  • The checkpoint clamp protein Rad9 facilitates DNA-end resection and prevents alternative non-homologous end joining. (nih.gov)
  • Checkpoint protein Rad9 plays an important role in nucleotide excision repair. (nih.gov)
  • See 5 reference sequence protein isoforms for the RAD9A gene. (nih.gov)
  • Combined with D-type (D1, D2, D3) cyclin, Cdk4/6 is activated and phosphorylates the retinoblastoma protein (Rb), promoting the escape of E2F from phosphorylated Rb, and therefore inducing cell transit from the G1 phase into the S phase. (spandidos-publications.com)
  • HRAD9B encodes a protein that is 414 amino acids long and is 55% similar and 35% identical to the HRAD9 gene product. (aacrjournals.org)
  • We demonstrate that the encoded human protein is nuclear and can physically interact with checkpoint proteins HRAD1, HRAD9, HHUS1, and HHUS1B, much like HRAD9. (aacrjournals.org)
  • The encoded protein is structurally related to the HHUS1 gene product and can coimmunoprecipitate with tagged HRAD9, HRAD1, and HHUS1. (aacrjournals.org)
  • CHEK2 functions downstream of ATM (Ataxia-telangiectasia mutated) to phosphorylate several substrates, including TP53 (Tumour protein p53), Cdc25C (Cell division cycle 25C) and BRCA1 (Breast cancer 1, early onset), leading to cell cycle arrest, activation of DNA repair or apoptosis in response to DNA double-stranded breaks. (biomedcentral.com)
  • Using reverse transcription polymerase chain reactions and western blots, we found that overexpression of CUL4A in MCF7 and MDA-MB-468 cells up-regulated MDR1 / P-gp expression on both the transcription and protein levels, which conferred multidrug resistance to P-gp substrate drugs, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. (mdpi.com)
  • genome
  • However, the transfer of chloroplast genes into the nuclear genome is a prerequisite in this scheme, although it should not have been established during the very early phase of chloroplast evolution. (frontiersin.org)
  • In plant cells, three independent organelles - chloroplasts, mitochondria, and the nucleus - each contain their own genome. (frontiersin.org)
  • candidate genes
  • As part of an international breast cancer genetics study aiming to investigate candidate genes conferring an intermediate-risk of breast cancer, we mutation screened the coding exons and the adjacent proximal introns of CHEK2 in 1415 cases and 1204 controls. (biomedcentral.com)
  • cancers
  • The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. (biomedcentral.com)
  • Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1 , were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers and their neighboring normal tissues. (aacrjournals.org)
  • To elucidate the frequency and physiological consequences of nonmutational silencing of mitotic checkpoint genes in human colorectal cancers, we have established hBUB1/hBUBR1 LightCycler RT-PCR 3 for accurate quantification of their transcripts and determined the expression levels in surgically resected cancer tissues and their neighboring normal colonic mucosa. (aacrjournals.org)
  • tumor cells
  • 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)
  • One essential strategy for cancer therapy is to activate apoptotic pathways in the tumor cells. (frontiersin.org)
  • The development of MDR, in which tumor cells become resistant to a wide spectrum of anti-cancer agents with different structures or different target sites, severely limits the success of chemotherapy in breast cancer [ 3 , 4 , 6 , 7 ]. (mdpi.com)
  • inhibitors
  • Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. (biomedcentral.com)
  • This review, for the first time, outlines the most important pre-clinical and clinical data available on the efficacy of cell cycle checkpoint inhibitors in single agent and in combination with different agents normally used for the treatment of acute and chronic leukemias. (biomedcentral.com)
  • dependent
  • These studies have demonstrated that relationships between DNA methylation and gene expression are much more complex than previously assumed and often highly dependent on the context of the gene region, the surrounding chromatin epigenetics, and the cell type [ 8 , 9 , 10 ]. (mdpi.com)
  • Ball HL, Cortez D (2005) ATRIP oligomerization is required for ATR-dependent checkpoint signaling. (springer.com)
  • epigenetic
  • Liu TX, Becker MW, Jelinek J et al (2007) Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. (springer.com)
  • DNA modifications, such as methylation of cytosine residues in CpG sequences, e.g. , are well documented to correlate with epigenetic gene silencing. (aacrjournals.org)
  • chromosomal
  • This results in gross chromosomal rearrangements that can lead to cell death or, when less severe, tumorigenesis via activation of oncogenes and loss of tumor suppressors. (genetics.org)
  • activation
  • Loss of either NONO or PER abolished this activation and circadian expression of p16-Ink4A and eliminated circadian cell cycle gating. (pnas.org)
  • We showed that activation of Notch-1 maintains the neoplastic phenotype and induces Notch-4 in Ras-transformed human fibroblasts and kidney epithelial cells ( 18 ). (aacrjournals.org)
  • The activation of cell cycle and checkpoint pathways in well-differentiated/dedifferentiated liposarcoma provides several possible novel therapeutic strategies with MDM2 serving as a particularly promising target. (aacrjournals.org)
  • Humans
  • 2008-11-29 00:00:00 Permanent lines of pluripotent stem cells can be obtained from humans and monkeys using different techniques and from different sources-inner cell mass of the blastocyst, primary germ cells, parthenogenetic oocytes, and mature spermatogonia-as well as by transgenic modification of various adult somatic cells. (deepdyve.com)
  • mammals
  • In mammals, individual clocks in most cells are synchronized by a brain "master clock" in the suprachiasmatic nucleus of the hypothalamus to orchestrate all rhythmic physiology ( 2 ). (pnas.org)
  • The primary advantages of the Drosophila system for use in anti‐cancer drug screening are the conservation of cancer genes/pathways between flies and mammals, its suitability for rapid phenotypic screening of chemicals for anti‐cancer effects in vivo in a high‐throughput and cost‐effective manner and its use in identifying drugs that can specifically target tumours in vivo . (els.net)
  • In most mammals, cycles of the addition and removal of DNA methylation constitute phases of reprogramming when the developing embryo must negotiate lineage defining and developmental commitment events. (springer.com)
  • clamp
  • In terms of cell cycle checkpoint control, several groups have suggested that HRAD9-HHUS1-HRAD1 form a proliferating cell nuclear antigen-like heterotrimer clamp, sometimes referred to as the 9-1-1 complex (4) , that is recruited onto damaged DNA via a clamp loader function of HRAD17. (aacrjournals.org)
  • human
  • Rapid self-renewal of human embryonic stem (ES) cells (NIH designation WA01 and WA09) is accommodated by an abbreviated cell cycle due to a reduction in the G1 phase. (umassmed.edu)
  • Here we show that the selective cell cycle regulated expression of individual histone H4 gene copies, which is typical for somatic cell types, is already firmly established in human ES cells. (umassmed.edu)
  • Bhandari P and Shashidhara LS (2001) Studies on human colon cancer gene APC by targeted expression in Drosophila. (els.net)
  • Ronski K, Sanders M, Burleson JA et al (2005) Early growth response gene 1 (EGR1) is deleted in estrogen receptor-negative human breast carcinoma. (springer.com)
  • Northern blot analysis to detect tissue specificity indicates that the human and mouse genes are expressed predominantly in the testis. (aacrjournals.org)
  • Furthermore, overexpression of HHUS1B in human 293 cells causes significant loss of clonogenicity, whereas similar studies with HHUS1 reveal no such effect. (aacrjournals.org)
  • failure
  • Failure to establish this checkpoint results in catastrophic mitoses, where acentric chromosome fragments are lost and incompletely repaired chromosomes fail to segregate. (genetics.org)
  • Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. (hindawi.com)
  • Pathologies, as atherosclerosis, cardiac fibrosis, and cardiomyopathy, are often linked to the failure of cardiovascular tissue cells to reenter the cell cycle, namely, senescence, due to endogenous or exogenous causes. (hindawi.com)
  • Inhibitor
  • Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAF V600E mutation and PTEN loss, and H3, harboring WT (wild-type) BRAF and PTEN loss, with the MAPK (BRAF) inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. (mdpi.com)
  • Moreover, ERK1/2 in CUL4A -overexpressing cells was highly activated and after treatment with PD98059, an ERK1/2-specific inhibitor, CUL4A -induced expression of MDR1 / P-gp was decreased significantly. (mdpi.com)
  • germ
  • Despite different origin, all pluripotent lines demonstrate considerable similarity of the major biological properties: active self-renewal and differentiation into various somatic and germ cells in vitro and in vivo, similar gene expression profiles, and similar cell cycle structure. (deepdyve.com)
  • inhibitory
  • Furthermore, a strong inhibitory effect on the viability of H1_DL2 cells, when grown as 3D multicellular spheroids, was seen. (mdpi.com)
  • chromatin
  • For representative genes, we illustrate relationships between DNA methylation, the local chromatin state, DNaseI hypersensitivity, and gene expression. (mdpi.com)
  • For example, MARVELD2 exhibited myogenic hypermethylation in transcription-type chromatin that overlapped a silenced promoter in Mb and Mt while TEAD4 had myogenic hypomethylation in intronic subregions displaying enhancer-type or transcription-type chromatin in these cells. (mdpi.com)