ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation.

Abstract:

:H2AX phosphorylation is an early step in the response to DNA damage. It is widely accepted that ATM (ataxia telangiectasia mutated protein) phosphorylates H2AX in response to DNA double-strand breaks (DSBs). Whether DNA-dependent protein kinase (DNA-PK) plays any role in this response is unclear. Here, we show that H2AX phosphorylation after exposure to ionizing radiation (IR) occurs to similar extents in human fibroblasts and in mouse embryo fibroblasts lacking either DNA-PK or ATM but is ablated in ATM-deficient cells treated with LY294002, a drug that specifically inhibits DNA-PK. Additionally, we show that inactivation of both DNA-PK and ATM is required to ablate IR-induced H2AX phosphorylation in chicken cells. We confirm that H2AX phosphorylation induced by DSBs in nonreplicating cells is ATR (ataxia telangiectasia and Rad3-related protein) independent. Taken together, we conclude that under most normal growth conditions, IR-induced H2AX phosphorylation can be carried out by ATM and DNA-PK in a redundant, overlapping manner. In contrast, DNA-PK cannot phosphorylate other proteins involved in the checkpoint response, including chromatin-associated Rad17. However, by phosphorylating H2AX, DNA-PK can contribute to the presence of the damage response proteins MDC1 and 53BP1 at the site of the DSB.

journal_name

Cancer Res

journal_title

Cancer research

authors

Stiff T,O'Driscoll M,Rief N,Iwabuchi K,Löbrich M,Jeggo PA

doi

10.1158/0008-5472.can-03-3207

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

2390-6

issue

7

eissn

0008-5472

issn

1538-7445

journal_volume

64

pub_type

杂志文章
  • Bcr interacts with components of the endosomal sorting complex required for transport-I and is required for epidermal growth factor receptor turnover.

    abstract::Virtually all patients with chronic myelogenous leukemia (CML) express an aberrant protein (p210 Bcr-Abl) that contains NH2-terminal sequences from Bcr fused to COOH-terminal sequences from Abl. In a yeast two-hybrid screen, we have identified TSG101 as a binding partner for Bcr. Because TSG101 is a subunit of the mam...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0536

    authors: Olabisi OO,Mahon GM,Kostenko EV,Liu Z,Ozer HL,Whitehead IP

    更新日期:2006-06-15 00:00:00

  • Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment.

    abstract::Determination of neopterin [D-erythro-6-(1',2',3'-trihydroxypropyl)pterin] in body fluids is a powerful diagnostic tool in a variety of diseases in which activation of cellular immune mechanisms is involved, such as certain malignancies, allograft rejection, and autoimmune and infectious diseases. In vitro, neopterin ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Werner-Felmayer G,Werner ER,Fuchs D,Hausen A,Reibnegger G,Wachter H

    更新日期:1990-05-15 00:00:00

  • Ca2(+)-dependent binding of tamoxifen to calmodulin isolated from bovine brain.

    abstract::The interaction of the antiestrogen tamoxifen (Tx) with calmodulin (CaM) was investigated by cross-linking between the protein and [3H] tamoxifen aziridine. We observed that CaM binds Tx in a Ca2(+)-dependent manner and that two components are involved in the binding, with apparent dissociation constants (Kd) of about...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Lopes MC,Vale MG,Carvalho AP

    更新日期:1990-05-01 00:00:00

  • Apo2 ligand/TNF-related apoptosis-inducing ligand and death receptor 5 mediate the apoptotic signaling induced by ionizing radiation in leukemic cells.

    abstract::Ionizing radiation is a major tool for cancer treatment. The response of eukaryotic cells to ionizing radiation includes apoptosis, a process which requires activation of multiple genes. We sought to determine whether radiation-induced gene expression plays a role in radiation-induced apoptosis. We found Apo2 ligand (...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gong B,Almasan A

    更新日期:2000-10-15 00:00:00

  • miRNA-95 mediates radioresistance in tumors by targeting the sphingolipid phosphatase SGPP1.

    abstract::Radiation resistance poses a major clinical challenge in cancer treatment, but little is known about how microRNA (miR) may regulate this phenomenon. In this study, we used next-generation sequencing to perform an unbiased comparison of miR expression in PC3 prostate cancer cells rendered resistant to fractionated rad...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-1657

    authors: Huang X,Taeb S,Jahangiri S,Emmenegger U,Tran E,Bruce J,Mesci A,Korpela E,Vesprini D,Wong CS,Bristow RG,Liu FF,Liu SK

    更新日期:2013-12-01 00:00:00

  • Differential effects of bryostatin 1 and phorbol ester on human breast cancer cell lines.

    abstract::The effects of the protein kinase C (PKC) activators, phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) and the marine natural product, bryostatin 1, on the growth and morphology of human breast cancer cell lines were examined. TPA (1 to 100 nM) inhibited growth of four of six cell lines by up to 75% in 5-day ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kennedy MJ,Prestigiacomo LJ,Tyler G,May WS,Davidson NE

    更新日期:1992-03-01 00:00:00

  • Mechanistic investigation and implications of photodynamic therapy induction of vascular endothelial growth factor in prostate cancer.

    abstract::Photodynamic therapy (PDT) is now an approved therapeutic modality, and induction of vascular endothelial growth factor (VEGF) following subcurative PDT is of concern as VEGF may provide a survival stimulus to tumors. The processes that limit the efficacy of PDT warrant investigation so that mechanism-based interventi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0604

    authors: Solban N,Selbo PK,Sinha AK,Chang SK,Hasan T

    更新日期:2006-06-01 00:00:00

  • Comparative analysis of the membrane proteome of closely related metastatic and nonmetastatic tumor cells.

    abstract::The identification of proteins that are preferentially expressed on the membrane of metastatic tumor cells is of fundamental importance in cancer research. Here, we report the systematic comparison of the membrane proteome of two closely related murine teratocarcinoma cell lines (F9B9 and F9DR), of which only one (F9D...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-0999

    authors: Roesli C,Borgia B,Schliemann C,Gunthert M,Wunderli-Allenspach H,Giavazzi R,Neri D

    更新日期:2009-07-01 00:00:00

  • Snail1-expressing fibroblasts in the tumor microenvironment display mechanical properties that support metastasis.

    abstract::Crosstalk between tumor and stromal cells in the tumor microenvironment alter its properties in ways that facilitate the invasive behavior of tumor cells. Here, we demonstrate that cancer-associated fibroblasts (CAF) increase the stiffness of the extracellular matrix (ECM) and promote anisotropic fiber orientation, tw...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-1903

    authors: Stanisavljevic J,Loubat-Casanovas J,Herrera M,Luque T,Peña R,Lluch A,Albanell J,Bonilla F,Rovira A,Peña C,Navajas D,Rojo F,García de Herreros A,Baulida J

    更新日期:2015-01-15 00:00:00

  • Cytochrome P450c17alpha gene (CYP17) polymorphism predicts use of hormone replacement therapy.

    abstract::We investigated whether a polymorphism in the cytochrome P450c17alpha gene (CYP17), which is associated with higher endogenous hormone levels, influences the use of hormone replacement therapy (HRT). The study included 749 postmenopausal women ages 44-75 years at baseline randomly selected from a larger multiethnic co...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Feigelson HS,McKean-Cowdin R,Pike MC,Coetzee GA,Kolonel LN,Nomura AM,Le Marchand L,Henderson BE

    更新日期:1999-08-15 00:00:00

  • Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment.

    abstract::Despite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2281

    authors: Harlin H,Meng Y,Peterson AC,Zha Y,Tretiakova M,Slingluff C,McKee M,Gajewski TF

    更新日期:2009-04-01 00:00:00

  • Improved growth of in vitro colonies in human acute leukemia with the feeding culture method.

    abstract::Bone marrow cells freshly aspirated from the 10 consecutive untreated adult patients with acute nonlymphocytic leukemia were cultured by 2 different methods: the conventional agar culture method for myeloid colony formation and its modification by daily feeding with culture medium. In 5 patients, colonies grew in much...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Park CH,Savin MA,Hoogstraten B,Amare M,Hathaway P

    更新日期:1977-12-01 00:00:00

  • Five loci, SLT1 to SLT5, controlling the susceptibility to spontaneously occurring lung cancer in mice.

    abstract::A series of linkage studies was previously conducted to identify quantitative trait loci associated with chemically induced lung tumors. However, little is known of genetic susceptibility to spontaneously occurring lung tumorigenesis (SLT) in mice. In this study, we did a whole-genome linkage disequilibrium analysis f...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-1508

    authors: Wang D,You M

    更新日期:2005-09-15 00:00:00

  • Simultaneous infiltration of polyfunctional effector and suppressor T cells into renal cell carcinomas.

    abstract::Renal cell carcinoma is frequently infiltrated by cells of the immune system. This makes it important to understand interactions between cancer cells and immune cells so they can be manipulated to bring clinical benefit. Here, we analyze subsets and functions of T lymphocytes infiltrating renal cell tumors directly ex...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-0852

    authors: Attig S,Hennenlotter J,Pawelec G,Klein G,Koch SD,Pircher H,Feyerabend S,Wernet D,Stenzl A,Rammensee HG,Gouttefangeas C

    更新日期:2009-11-01 00:00:00

  • Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines.

    abstract::Glutamine supplementation has been advocated for patients requiring parenteral nutritional support. However, the direct effect of glutamine on neoplastic cells is poorly understood. We therefore investigated the effects of glutamine on the proliferation, differentiation, and cell-matrix interactions of two human colon...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Turowski GA,Rashid Z,Hong F,Madri JA,Basson MD

    更新日期:1994-11-15 00:00:00

  • Different ionic forms of estrogen receptor in rat uterus and human breast carcinoma.

    abstract::Estrogen receptors from rat uterus and human breast carcinoma were analyzed by diethylaminoethyl-cellulose chromatography. Cytosols which had been incubated for short periods of time demonstrated a single discrete elution peak, indicating a single ionic form, while cytosols incubated for longer periods of time generat...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Tilzer LL,McFarland RT,Plapp FV,Evans JP,Chiga M

    更新日期:1981-03-01 00:00:00

  • Preparation of permanent slides of intact soft-agar colony cultures of hematopoietic and tumor stem cells.

    abstract::A simple technique is described for fixing colony-containing layers of soft agar and drying them onto microscopic slides. The method is extrapolated from techniques used in immunology for permanent preservation of immunodiffusion or immunoelectrophoresis plates. Slides prepared in this fashion are eminently suitable f...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Salmon SE,Buick RN

    更新日期:1979-03-01 00:00:00

  • Molecular mechanisms of RET receptor-mediated oncogenesis in multiple endocrine neoplasia 2B.

    abstract::Multiple endocrine neoplasia 2B (MEN 2B) is an inherited syndrome of early onset endocrine tumors and developmental anomalies. The disease is caused primarily by a methionine to threonine substitution of residue 918 in the kinase domain of the RET receptor (2B-RET); however, the molecular mechanisms that lead to the d...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3329

    authors: Gujral TS,Singh VK,Jia Z,Mulligan LM

    更新日期:2006-11-15 00:00:00

  • Growth and spread in nude mice of Epstein-Barr virus transformed B-cells from a chronic lymphocytic leukemia patient.

    abstract::Subcutaneous inoculation of Epstein-Barr virus (EBV) transformed peripheral blood B-lymphocytes (PBL) from an untreated chronic lymphocytic leukemia (CLL) patient produced progressively growing lethal tumors in 4 of 11 whole body irradiated (440 rads) nude mice. In one tumor bearing mouse there was splenomegaly and ge...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Lee CL,Uniyal S,Fernandez LA,Lee SH,Ghose T

    更新日期:1986-05-01 00:00:00

  • Isolation and characterization of a complementary DNA clone for a Mr 32,000 protein which is induced with tumor promoters in BALB/c 3T3 cells.

    abstract::The synthesis of a protein of Mr 32,000 (p32) is enhanced by various tumor promoters, chemical carcinogens, metal salts, and heat shock in BALB/c 3T3 cells. We have isolated a complementary DNA (cDNA) clone for p32 from a lambda gt10 library of BALB/c 3T3 cells. The library was constructed from mRNA extracted from the...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kageyama H,Hiwasa T,Tokunaga K,Sakiyama S

    更新日期:1988-09-01 00:00:00

  • Induction of human monocyte susceptibility to lymphokine-activated killer cell lysis by granulocyte-macrophage colony-stimulating factor.

    abstract::We have recently reported that cultured human monocytes are susceptible to lysis by autologous lymphokine-activated killer (LAK) cells. In an attempt to modulate the sensitivity of monocytes to LAK-mediated lysis, monocytes were cultured in the presence of recombinant human granulocyte-macrophage colony-stimulating fa...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Blanchard DK,Serbousek D,Djeu JY

    更新日期:1989-09-15 00:00:00

  • Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885.

    abstract::Oncogenic BRAF alleles are both necessary and sufficient for cellular transformation, suggesting that chemical inhibition of the activated mutant protein kinase may reverse the tumor phenotype. Here, we report the characterization of SB-590885, a novel triarylimidazole that selectively inhibits Raf kinases with more p...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-2554

    authors: King AJ,Patrick DR,Batorsky RS,Ho ML,Do HT,Zhang SY,Kumar R,Rusnak DW,Takle AK,Wilson DM,Hugger E,Wang L,Karreth F,Lougheed JC,Lee J,Chau D,Stout TJ,May EW,Rominger CM,Schaber MD,Luo L,Lakdawala AS,Adams JL,

    更新日期:2006-12-01 00:00:00

  • Interaction of E-cadherin and PTEN regulates morphogenesis and growth arrest in human mammary epithelial cells.

    abstract::Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a dual-function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintena...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-1694

    authors: Fournier MV,Fata JE,Martin KJ,Yaswen P,Bissell MJ

    更新日期:2009-05-15 00:00:00

  • Use of cardiac troponin T levels as an indicator of doxorubicin-induced cardiotoxicity.

    abstract::The release of cardiac troponin T (cTnT) as a biomarker of doxorubicin-induced chronic cardiac injury was evaluated in the spontaneously hypertensive rat (SHR) model. Elevations in serum levels of cTnT and decreased immunohistochemical staining of heart sections for this protein were noted in SHRs treated with cumulat...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Herman EH,Lipshultz SE,Rifai N,Zhang J,Papoian T,Yu ZX,Takeda K,Ferrans VJ

    更新日期:1998-01-15 00:00:00

  • Tumor-immune dynamics regulated in the microenvironment inform the transient nature of immune-induced tumor dormancy.

    abstract::Cancer in a host induces responses that increase the ability of the microenvironment to sustain the growing mass, for example, angiogenesis, but cancer cells can have varying sensitivities to these sustainability signals. Here, we show that these sensitivities are significant determinants of ultimate tumor fate, espec...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-4590

    authors: Wilkie KP,Hahnfeldt P

    更新日期:2013-06-15 00:00:00

  • Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes.

    abstract::Recent reports have variously described expression of Fas ligand (FasL) or its absence in human tumors. The importance of the Fas-FasL mechanism for the immune evasion by tumors provided a strong rationale for the examination of FasL expression and function in squamous cell carcinoma of the head and neck (SCCHN), whic...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gastman BR,Atarshi Y,Reichert TE,Saito T,Balkir L,Rabinowich H,Whiteside TL

    更新日期:1999-10-15 00:00:00

  • Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A, transporter 2 (ABCA2).

    abstract::We have isolated the full-length cDNA for human ATP-binding cassette, sub-family A, member 2 transporter (ABCA2). The ORF of this cDNA encodes a protein consisting of 2436 amino acids with apparent molecular weight of M(r) 270,000. Accordingly, ABCA2 is the largest known mammalian ABC transporter described thus far. A...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Vulevic B,Chen Z,Boyd JT,Davis W Jr,Walsh ES,Belinsky MG,Tew KD

    更新日期:2001-04-15 00:00:00

  • Suppression of Bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor alpha, and ceramide.

    abstract::Recent studies have proposed that tumor necrosis factor alpha (TNF-alpha) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apop...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chen M,Quintans J,Fuks Z,Thompson C,Kufe DW,Weichselbaum RR

    更新日期:1995-03-01 00:00:00

  • Imaging techniques for the radioimmunodetection of cancer.

    abstract::Problems in the radioimmunodetection of cancer typically involve small lesions having low object contrast. As such, the imaging device utilized must have a high spatial resolution as well as high detection efficiency. In addition, the imaging device must be interfaced to a computer system to allow data manipulation to...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rollo FD,Patton JA

    更新日期:1980-08-01 00:00:00

  • Lectin-binding proteins in nuclear preparations from rat liver and malignant tumors.

    abstract::Lectin binding [concanavalin A, biotinylated ricinus communis agglutinin, and biotinylated succinylated wheat germ agglutinin (B-SWGA)] was used to detect the glycosylated proteins associated with a residual protein fraction [insoluble in 4% sodium dodecyl sulfate and termed the nuclear residual fraction (NRF)] or wit...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Burrus GR,Schmidt WN,Briggs JA,Hnilica LS,Briggs RC

    更新日期:1988-02-01 00:00:00