Search results for: ATM (Ab 1981)
#19884805 // To Up
DNA damage repair and telomere length in normal breast, preneoplastic lesions, and invasive cancer.Carcinogenesis is a multistep process involving the accumulation of genetic and molecular abnormalities. It has been suggested that there is a relationship between telomere attrition in the early stages of carcinogenesis and activation of the DNA damage response machinery. We explored telomere length modification and damage response pathway activation at 3 steps of breast carcinogenesis.
Christophe M Raynaud, Juana Hernandez, FrÃ©dÃ©rique P Llorca, Paolo Nuciforo, Marie-Christine Mathieu, Frederic Commo, Suzette Delaloge, Laure Sabatier, Fabrice AndrÃ©, Jean-Charles Soria
2827 related Products with: DNA damage repair and telomere length in normal breast, preneoplastic lesions, and invasive cancer.
#17200553 // To Up
Utilizing protein phosphatase inhibitors to define PP2A as a regulator of ataxia-telangiectasia mutated.Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase that plays a central role in controlling the cellular response to DNA double-strand breaks caused by ionizing radiation. Ionizing radiation induces the autophosphorylation of ATM on serine 1981; however, the precise mechanisms that regulate ATM autophosphorylation are not fully understood. By treating cells with okadaic acid, a cell-permeable protein phosphatase inhibitor, together with assays to quantify the activity of particular protein phosphatases, we have demonstrated that the autophosphorylation of ATM on serine 1981 is regulated by a protein phosphatase 2A-like activity. Here, we describe the series of experiments that employed protein phosphatase inhibitors to establish that ATM was regulated by a type-2A protein phosphatase.
Aaron A Goodarzi, Pauline Douglas, Greg B G Moorhead, Susan P Lees-Miller
2958 related Products with: Utilizing protein phosphatase inhibitors to define PP2A as a regulator of ataxia-telangiectasia mutated.1 kit(96 Wells)50 assays500 assays430 tests100ug1 kit1 kit(96 Wells) 100ul100 assays 100ul96
#16528719 // To Up
Effects of hydroxyurea and aphidicolin on phosphorylation of ataxia telangiectasia mutated on Ser 1981 and histone H2AX on Ser 139 in relation to cell cycle phase and induction of apoptosis.DNA replication stress often induces DNA damage. The antitumor drug hydroxyurea (HU), a potent inhibitor of ribonucleotide reductase that halts DNA replication through its effects on cellular deoxynucleotide pools, was shown to damage DNA inducing double-strand breaks (DSBs). Aphidicolin (APH), an inhibitor of alpha-like DNA polymerases, was also reported to cause DNA damage, but the evidence for induction of DSBs by APH is not straightforward. Histone H2AX is phosphorylated on Ser 139 in response to DSBs and one of the protein kinases that phosphorylate H2AX is ataxia telangiectasia mutated (ATM); activation of ATM is through its phosphorylation of Ser 1981. The present study was undertaken to reveal whether H2AX is phosphorylated in cells exposed to HU or APH and whether its phosphorylation is mediated by ATM.
Akira Kurose, Toshiki Tanaka, Xuan Huang, Frank Traganos, Wei Dai, Zbigniew Darzynkiewicz
1570 related Products with: Effects of hydroxyurea and aphidicolin on phosphorylation of ataxia telangiectasia mutated on Ser 1981 and histone H2AX on Ser 139 in relation to cell cycle phase and induction of apoptosis.100ug50 ug 100ug96T50 ug 100ug100ug2 Pieces/Box100 ul100 ul100 ul100ug
#16426903 2006/01/19 To Up
Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity.Double strand DNA breaks in the genome lead to the activation of the ataxia-telangiectasia mutated (ATM) kinase in a process that requires ATM autophosphorylation at serine-1981. ATM autophosphorylation only occurs if ATM is previously acetylated by Tip60. The activated ATM kinase phosphorylates proteins involved in arresting the cell cycle, including p53, and in repairing the DNA breaks. Chloroquine treatment and other manipulations that produce chromatin defects in the absence of detectable double strand breaks also trigger ATM phosphorylation and the phosphorylation of p53 in primary human fibroblasts, while other downstream substrates of ATM that are involved in the repair of DNA double strand breaks remain unphosphorylated. This raises the issue of whether ATM is constitutively activated in patients with genetic diseases that display chromatin defects. We examined lymphoblastoid cell lines (LCLs) generated from patients with different types of chromatin disorders: Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, Coffin Lowry syndrome, Rubinstein Taybi syndrome and Fascioscapulohumeral Muscular Dystrophy. We show that ATM is phosphorylated on serine-1981 in LCLs derived from ICF patients but not from the other syndromes. The phosphorylated ATM in ICF cells did not phosphorylate the downstream targets NBS1, SMC1 and H2AX, all of which require the presence of double strand breaks. We demonstrate that ICF cells respond normally to ionizing radiation, ruling out the possibility that genetic deficiency in ICF cells renders activated ATM incapable of phosphorylating its downstream substrates. Surprisingly, p53 was also not phosphorylated in ICF cells or in chloroquine-treated wild type LCLs. In this regard the response to chromatin-altering agents differs between primary fibroblasts and LCLs. Our findings indicate that although phosphorylation at serine-1981 is essential in the activation of the ATM kinase, serine-1981 phosphorylation is insufficient to render ATM an active kinase towards downstream substrates, including p53.
Jimena V Goldstine, Shareef Nahas, Kristin Gamo, Stanley M Gartler, R Scott Hansen, Jeroen H Roelfsema, Richard A Gatti, York Marahrens
1911 related Products with: Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity.2 Pieces/Box2 Pieces/Box1 kit400Tests2 Pieces/Box1 kit2 Pieces/Box10 plates96Tcase
#16184611 // To Up
Assessment of ATM phosphorylation on Ser-1981 induced by DNA topoisomerase I and II inhibitors in relation to Ser-139-histone H2AX phosphorylation, cell cycle phase, and apoptosis.The ATM kinase regulates cell-cycle checkpoints by phosphorylating multiple proteins, including histone H2AX, CHK1, and CHK2 kinases and p53. ATM is activated through auto- or trans- phosphorylation of Ser-1981 in response to DNA damage, particularly induction of DNA double-strand breaks (DSBs). The aim of the present study was to reveal a possible correlation between activation of ATM vis-Ã -vis H2AX phosphorylation, cell cycle phase, and apoptosis in cells treated with DNA topoisomerase (topo) I (topotecan; Tpt) or topo2 (mitoxantrone; Mtx) inhibitor.
Akira Kurose, Toshiki Tanaka, Xuan Huang, H Dorota Halicka, Frank Traganos, Wei Dai, Zbigniew Darzynkiewicz
2208 related Products with: Assessment of ATM phosphorylation on Ser-1981 induced by DNA topoisomerase I and II inhibitors in relation to Ser-139-histone H2AX phosphorylation, cell cycle phase, and apoptosis.2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box500 gm.2 Pieces/Box2 Pieces/Box100 ul3 inhibitors2 Pieces/Box100 ul
#15510216 2004/10/28 To Up
Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A.Ionizing radiation induces autophosphorylation of the ataxia-telangiectasia mutated (ATM) protein kinase on serine 1981; however, the precise mechanisms that regulate ATM activation are not fully understood. Here, we show that the protein phosphatase inhibitor okadaic acid (OA) induces autophosphorylation of ATM on serine 1981 in unirradiated cells at concentrations that inhibit protein phosphatase 2A-like activity in vitro. OA did not induce gamma-H2AX foci, suggesting that it induces ATM autophosphorylation by inactivation of a protein phosphatase rather than by inducing DNA double-strand breaks. In support of this, we show that ATM interacts with the scaffolding (A) subunit of protein phosphatase 2A (PP2A), that the scaffolding and catalytic (C) subunits of PP2A interact with ATM in undamaged cells and that immunoprecipitates of ATM from undamaged cells contain PP2A-like protein phosphatase activity. Moreover, we show that IR induces phosphorylation-dependent dissociation of PP2A from ATM and loss of the associated protein phosphatase activity. We propose that PP2A plays an important role in the regulation of ATM autophosphorylation and activity in vivo.
Aaron A Goodarzi, Jyoti C Jonnalagadda, Pauline Douglas, David Young, Ruiqiong Ye, Greg B G Moorhead, Susan P Lees-Miller, Kum Kum Khanna
2764 related Products with: Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A.100 ul100ug Lyophilized0.1ml (1mg/ml)100ug Lyophilized20000 U100ul100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug Lyophilized100ug100ug Lyophilized
#15177184 // To Up
Biochemical characterization of the ataxia-telangiectasia mutated (ATM) protein from human cells.Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase that plays a central role in controlling the cellular response to ionizing radiation and other DNA-damaging agents. ATM is a 3056 amino acid polypeptide that is present in low abundance in the nucleus of human cells. Here, we describe the purification and characterization of ATM from the nuclear fraction of HeLa cells. Microgram quantities of highly stable, kinase-active ATM were prepared. Purified ATM was phosphorylated on serine 1981 and was active towards a variety of known ATM substrates, including p53 and the Bloom Syndrome helicase, BLM. The protein kinase activity of ATM was selectively inhibited by wortmannin, caffeine and LY294002 and was stimulated by charged biological polymers, including single-stranded M13 DNA (ssDNA), sheared double-stranded calf thymus DNA, heparin sulfate and poly ADP-ribose (PAR), raising the possibility that charged structures may contribute to regulation of ATM activity. However, chemical inhibition of the formation of poly ADP-ribose in cells had no effect on the activation of ATM-dependent pathways by ionizing radiation. Using gel filtration chromatography, we also show that purified ATM, as well as ATM in crude nuclear extracts from unirradiated and irradiated cells elutes with an estimated native molecular weight of approximately 600 kDa. Moreover, dephosphorylation of serine 1981 did not affect the apparent molecular weight of ATM in irradiated extracts. Our results suggest that phosphorylation of serine 1981 alone may not directly regulate the subunit composition of ATM.
Aaron A Goodarzi, Susan P Lees-Miller
2229 related Products with: Biochemical characterization of the ataxia-telangiectasia mutated (ATM) protein from human cells.1mg1mg21021mg1021mg1mg102
#7236475 // To Up
Chromosomal and teratogenic effects of oxygen in the mouse.The effect of oxygen on chromosomes in bone marrow cells and on the early stages of gestation in the mouse were studied. Three groups of male mice were exposed to hyperbaric oxygen at 2, 3 and 4 atm abs. for 1 h, and four other groups breathed pure oxygen at 1 atm abs, for 6, 12, 24 and 48 h respectively. Chromosome were studied after 24 h. In the pure oxygen groups, no significant increase in chromosome aberration was noted, but in the hyperbaric oxygen groups, significant increases in abnormalities (breakage and gap) were noted at 3 and 4 atm abs. (8.0 and 6.7% respectively, P less than 0.05). In another study, four groups of pregnant mice were exposed once to hyperbaric oxygen at either 2 atm abs. for 1 h on the 7th or 8th day of gestation, or 2.5 atm abs. for 2 h on the 5th or 8th day. Six other groups were exposed to 2, 3 and 3.5 atm abs. with either oxygen or air for 1 h daily during first 8 days of gestation. Malformations (umbilical hernia and abnormalities of the coccyx) in the newborn were noted in the groups exposed to hyperbaric oxygen at 2.5 atm abs. for 2 h on the 5th and 8th days of gestation (1/26, 7/42), and all the groups exposed daily to hyperbaric oxygen (1/58, 3/33, 2/24). These findings would seem to indicate a genetic effect of increased oxygen tension in vitro.
T Yusa100.00 ug2ug32-50 Sample Kit100.00 ug1 kit(96 Wells)100 μg100 μg100ug Lyophilized5ug100.00 ug100.00 ug100ug Lyophilized
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