Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways.


:TRAIL is an endogenous death receptor ligand also used therapeutically because of its selective proapoptotic activity in cancer cells. In the present study, we examined chromatin alterations induced by TRAIL and show that TRAIL induces a rapid activation of DNA damage response (DDR) pathways with histone H2AX, Chk2, ATM, and DNA-PK phosphorylations. Within 1 h of TRAIL exposure, immunofluorescence confocal microscopy revealed gamma-H2AX peripheral nuclear staining (gamma-H2AX ring) colocalizing with phosphorylated/activated Chk2, ATM, and DNA-PK inside heterochromatin regions. The marginal distribution of DDR proteins in early apoptotic cells is remarkably different from the focal staining seen after DNA damage. TRAIL-induced DDR was suppressed upon caspase inhibition or Bax inactivation, demonstrating that the DDR activated by TRAIL is downstream from the mitochondrial death pathway. H2AX phosphorylation was dependent on DNA-PK, while Chk2 phosphorylation was dependent on both ATM and DNA-PK. Downregulation of Chk2 decreased TRAIL-induced cell detachment; delayed the activation of caspases 2, 3, 8, and 9; and reduced TRAIL-induced cell killing. Together, our findings suggest that nuclear activation of Chk2 by TRAIL acts as a positive feedback loop involving the mitochondrion-dependent activation of caspases, independently of p53.


Mol Cell Biol


Solier S,Sordet O,Kohn KW,Pommier Y




Has Abstract


2009-01-01 00:00:00














  • Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors.

    abstract::The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G2/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the context of Sonic hed...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Schüller U,Zhao Q,Godinho SA,Heine VM,Medema RH,Pellman D,Rowitch DH

    更新日期:2007-12-01 00:00:00

  • The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination.

    abstract::E3 ubiquitin ligases, which target specific molecules for proteolytic destruction, have emerged as key regulators of immune functions. Several E3 ubiquitin ligases, including c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4, have been shown to negatively regulate T-cell activation. Here, we report that the HECT-type E3 ligase AIP...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chen A,Gao B,Zhang J,McEwen T,Ye SQ,Zhang D,Fang D

    更新日期:2009-10-01 00:00:00

  • Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.

    abstract::We constructed a series of recombinant genomes which directed expression of the enzyme chloramphenicol acetyltransferase (CAT) in mammalian cells. The prototype recombinant in this series, pSV2-cat, consisted of the beta-lactamase gene and origin of replication from pBR322 coupled to a simian virus 40 (SV40) early tra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Gorman CM,Moffat LF,Howard BH

    更新日期:1982-09-01 00:00:00

  • Characterization of the human interleukin-2 receptor beta-chain gene promoter: regulation of promoter activity by ets gene products.

    abstract::The interleukin-2 receptor (IL-2R) beta chain (IL-2R beta) is an essential signaling component of high- and intermediate-affinity IL-2Rs. Our laboratory previously reported that a DNA fragment containing 857 bp of 5'-flanking sequence of the human IL-2R beta gene exhibited promoter activity. We have now further charac...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lin JX,Bhat NK,John S,Queale WS,Leonard WJ

    更新日期:1993-10-01 00:00:00

  • When Long Noncoding Becomes Protein Coding.

    abstract::Recent advancements in genetic and proteomic technologies have revealed that more of the genome encodes proteins than originally thought possible. Specifically, some putative long noncoding RNAs (lncRNAs) have been misannotated as noncoding. Numerous lncRNAs have been found to contain short open reading frames (sORFs)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章,评审


    authors: Hartford CCR,Lal A

    更新日期:2020-02-27 00:00:00

  • RasGRF2, a guanosine nucleotide exchange factor for Ras GTPases, participates in T-cell signaling responses.

    abstract::The Ras pathway is critical for the development and function of T lymphocytes. The stimulation of this GTPase in T cells occurs primarily through the Vav1- and phospholipase C-gamma1-dependent activation of RasGRP1, a diacylglycerol-responsive Ras GDP/GTP exchange factor. Here, we show that a second exchange factor, R...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ruiz S,Santos E,Bustelo XR

    更新日期:2007-12-01 00:00:00

  • Endoplasmic reticulum stress accelerates p53 degradation by the cooperative actions of Hdm2 and glycogen synthase kinase 3beta.

    abstract::Inactivation of the tumor suppressor p53 by degradation is a mechanism utilized by cells to adapt to endoplasmic reticulum (ER) stress. However, the mechanisms of p53 destabilization by ER stress are not known. We demonstrate here that the E3 ubiquitin-ligase Hdm2 is essential for the nucleocytoplasmic transport and p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Pluquet O,Qu LK,Baltzis D,Koromilas AE

    更新日期:2005-11-01 00:00:00

  • Properties of Nat4, an N(alpha)-acetyltransferase of Saccharomyces cerevisiae that modifies N termini of histones H2A and H4.

    abstract::Nat4, also designated NatD, was previously shown to acetylate the N termini of histones H2A and H4, which have SGGKG and SGRGK N termini (O. K. Song, X. Wang, J. H. Waterborg, and R. Sternglanz, J. Biol. Chem. 278:38109-38112, 2003). The analysis of chimeric proteins with various N-terminal segments of histone H4 fuse...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Polevoda B,Hoskins J,Sherman F

    更新日期:2009-06-01 00:00:00

  • Functional and conserved domains of the Drosophila transcription factor encoded by the segmentation gene knirps.

    abstract::The Drosophila gap gene knirps (kni) is required for abdominal segmentation. It encodes a steroid/thyroid orphan receptor-type transcription factor which is distributed in a broad band of nuclei in the posterior region of the blastoderm. To identify essential domains of the kni protein (KNI), we cloned and sequenced t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Gerwin N,La Rosée A,Sauer F,Halbritter HP,Neumann M,Jäckle H,Nauber U

    更新日期:1994-12-01 00:00:00

  • Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation.

    abstract::Circadian clock genes are regulated through a transcriptional-translational feedback loop. Alterations of the chromatin structure by histone acetyltransferases and histone deacetylases (HDACs) are commonly implicated in the regulation of gene transcription. However, little is known about the transcriptional regulation...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Naruse Y,Oh-hashi K,Iijima N,Naruse M,Yoshioka H,Tanaka M

    更新日期:2004-07-01 00:00:00

  • Attenuation of late simian virus 40 mRNA synthesis is enhanced by the agnoprotein and is temporally regulated in isolated nuclear systems.

    abstract::Studies were performed to verify the physiological significance of attenuation in the life cycle of simian virus 40 and the role of agnoprotein in this process. For these purposes, nuclei were isolated at various times after infection and incubated in vitro in the presence of [alpha-32P]UTP under the standard conditio...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hay N,Aloni Y

    更新日期:1985-06-01 00:00:00

  • Neuroblastoma cells express c-sis and produce a transforming growth factor antigenically related to the platelet-derived growth factor.

    abstract::Mouse neuroblastoma Neuro-2A cells produce transforming growth factors during exponential growth in a defined hormone-free medium, which, on Bio-Gel columns in 1 M HAc, elute at a molecular size of 15 to 20 kilodaltons (kDa). These neuroblastoma-derived transforming growth factors have strong mitogenic activity, but t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: van Zoelen EJ,van de Ven WJ,Franssen HJ,van Oostwaard TM,van der Saag PT,Heldin CH,de Laat SW

    更新日期:1985-09-01 00:00:00

  • RYBP represses endogenous retroviruses and preimplantation- and germ line-specific genes in mouse embryonic stem cells.

    abstract::Polycomb repressive complexes (PRCs) are important chromatin regulators of embryonic stem (ES) cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B and has been suggested to assist PRC localization to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Usin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hisada K,Sánchez C,Endo TA,Endoh M,Román-Trufero M,Sharif J,Koseki H,Vidal M

    更新日期:2012-03-01 00:00:00

  • A Repertoire of MicroRNAs Regulates Cancer Cell Starvation by Targeting Phospholipase D in a Feedback Loop That Operates Maximally in Cancer Cells.

    abstract::We report a negative feedback loop between the signaling protein phospholipase D (PLD), phosphatidic acid (PA), and a specific set of microRNAs (miRNAs) during nutrient starvation of breast cancer cells. We show that PLD expression is increased in four breast cancer cell lines and that hypoxia, cell overcrowding, and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Fite K,Elkhadragy L,Gomez-Cambronero J

    更新日期:2016-01-19 00:00:00

  • Isolation and characterization of a novel epithelium-specific transcription factor, ESE-1, a member of the ets family.

    abstract::We report here the isolation of a novel, highly tissue-restricted member of the ets transcription factor/oncogene family, ESE-1 (for epithelium-specific Ets), which has features distinct from those of any other ets-related factor. ESE-1 contains two putative DNA binding domains: an ETS domain, which is unique in that ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Oettgen P,Alani RM,Barcinski MA,Brown L,Akbarali Y,Boltax J,Kunsch C,Munger K,Libermann TA

    更新日期:1997-08-01 00:00:00

  • MYC abrogates p53-mediated cell cycle arrest in N-(phosphonacetyl)-L-aspartate-treated cells, permitting CAD gene amplification.

    abstract::Genomic instability, including the ability to undergo gene amplification, is a hallmark of neoplastic cells. Similar to normal cells, "nonpermissive" REF52 cells do not develop resistance to N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of the synthesis of pyrimidine nucleotides, through amplification of cad, th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chernova OB,Chernov MV,Ishizaka Y,Agarwal ML,Stark GR

    更新日期:1998-01-01 00:00:00

  • Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes.

    abstract::The Myt1 protein kinase functions to negatively regulate Cdc2-cyclin B complexes by phosphorylating Cdc2 on threonine 14 and tyrosine 15. Throughout interphase, human Myt1 localizes to the endoplasmic reticulum and Golgi complex, whereas Cdc2-cyclin B1 complexes shuttle between the nucleus and the cytoplasm. Here we r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Liu F,Rothblum-Oviatt C,Ryan CE,Piwnica-Worms H

    更新日期:1999-07-01 00:00:00

  • Vav activation and function as a rac guanine nucleotide exchange factor in macrophage colony-stimulating factor-induced macrophage chemotaxis.

    abstract::Signal transduction mediated by phosphatidylinositol 3-kinase (PI 3-kinase) is regulated by hydrolysis of its products, a function performed by the 145-kDa SH2 domain-containing inositol phosphatase (SHIP). Here, we show that bone marrow macrophages of SHIP(-/-) animals have elevated levels of phosphatidylinositol 3,4...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Vedham V,Phee H,Coggeshall KM

    更新日期:2005-05-01 00:00:00

  • Modular recognition of 5-base-pair DNA sequence motifs by human heat shock transcription factor.

    abstract::We investigated the recognition of the conserved 5-bp repeated motif NGAAN, which occurs in heat shock gene promoters of Drosophila melanogaster and other eukaryotic organisms, by human heat shock transcription factor (HSF). Extended heat shock element mutants of the human HSP70 gene promoter, containing additional NG...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cunniff NF,Wagner J,Morgan WD

    更新日期:1991-07-01 00:00:00

  • Bcl-2 retards cell cycle entry through p27(Kip1), pRB relative p130, and altered E2F regulation.

    abstract::Independent of its antiapoptotic function, Bcl-2 can, through an undetermined mechanism, retard entry into the cell cycle. Cell cycle progression requires the phosphorylation by cyclin-dependent kinases (Cdks) of retinoblastoma protein (pRB) family members to free E2F transcription factors. We have explored whether re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Vairo G,Soos TJ,Upton TM,Zalvide J,DeCaprio JA,Ewen ME,Koff A,Adams JM

    更新日期:2000-07-01 00:00:00

  • Alternative splicing regulates Prdm1/Blimp-1 DNA binding activities and corepressor interactions.

    abstract::Prdm1/Blimp-1 is a master regulator of gene expression in diverse tissues of the developing embryo and adult organism. Its C-terminal zinc finger domain mediates nuclear import, DNA binding, and recruitment of the corepressors G9a and HDAC1/2. Alternatively spliced transcripts lacking exon 7 sequences encode a structu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Morgan MA,Mould AW,Li L,Robertson EJ,Bikoff EK

    更新日期:2012-09-01 00:00:00

  • Evidence for torsional stress in transcriptionally activated chromatin.

    abstract::The existence of torsional stress in eukaryotic chromatin has been controversial. To determine whether it could be detected, we probed the structure of an alternating AT tract. These sequences adopt cruciform geometry when the DNA helix is torsionally strained by negative supercoiling. The single-strand-specific nucle...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Leonard MW,Patient RK

    更新日期:1991-12-01 00:00:00

  • Phosphatidylinositol 3-kinase/Akt induced by erythropoietin renders the erythroid differentiation factor GATA-1 competent for TIMP-1 gene transactivation.

    abstract::The contribution of erythropoietin to the differentiation of the red blood cell lineage remains elusive, and the demonstration of a molecular link between erythropoietin and the transcription of genes associated with erythroid differentiation is lacking. In erythroid cells, expression of the tissue inhibitor of matrix...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kadri Z,Maouche-Chretien L,Rooke HM,Orkin SH,Romeo PH,Mayeux P,Leboulch P,Chretien S

    更新日期:2005-09-01 00:00:00

  • The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively.

    abstract::In Drosophila melanogaster, X chromosome dosage compensation is achieved by doubling the transcription of most X-linked genes. The male-specific lethal (MSL) complex is required for this process and binds to hundreds of sites on the male X chromosome. The MSL1 protein is essential for X chromosome binding and serves a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Li F,Parry DA,Scott MJ

    更新日期:2005-10-01 00:00:00

  • The Brn-2 transcription factor links activated BRAF to melanoma proliferation.

    abstract::Malignant melanoma, an aggressive and increasingly common cancer, is characterized by a strikingly high rate (70%) of mutations in BRAF, a key component of the mitogen-activated protein (MAP) kinase signaling pathway. How signaling events downstream from BRAF affect the underlying program of gene expression is poorly ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Goodall J,Wellbrock C,Dexter TJ,Roberts K,Marais R,Goding CR

    更新日期:2004-04-01 00:00:00

  • Inheritance of extrachromosomal rDNA in Physarum polycephalum.

    abstract::In the acellular slime mold Physarum polycephalum, the several hundred genes coding for rRNA are located on linear extrachromosomal DNA molecules of a discrete size, 60 kilobases. Each molecule contains two genes that are arranged in a palindromic fashion and separated by a central spacer region. We investigated how r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ferris PJ,Vogt VM,Truitt CL

    更新日期:1983-04-01 00:00:00

  • Disruption of the Rb--Raf-1 interaction inhibits tumor growth and angiogenesis.

    abstract::The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating mammalian cell cycle progression and inactivation of Rb is necessary for entry into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation of quiescent cells, facilitating the transition from G(1) phase to S phase. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Dasgupta P,Sun J,Wang S,Fusaro G,Betts V,Padmanabhan J,Sebti SM,Chellappan SP

    更新日期:2004-11-01 00:00:00

  • Casein kinase Iepsilon modulates the signaling specificities of dishevelled.

    abstract::Wnt signaling is critical to many aspects of development, and aberrant activation of the Wnt signaling pathway can cause cancer. Dishevelled (Dvl) protein plays a central role in this pathway by transducing the signal from the Wnt receptor complex to the beta-catenin destruction complex. Dvl also plays a pivotal role ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cong F,Schweizer L,Varmus H

    更新日期:2004-03-01 00:00:00

  • Cytoplasmic recycling of 60S preribosomal factors depends on the AAA protein Drg1.

    abstract::Allelic forms of DRG1/AFG2 confer resistance to the drug diazaborine, an inhibitor of ribosome biogenesis in Saccharomyces cerevisiae. Our results show that the AAA-ATPase Drg1 is essential for 60S maturation and associates with 60S precursor particles in the cytoplasm. Functional inactivation of Drg1 leads to an incr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Pertschy B,Saveanu C,Zisser G,Lebreton A,Tengg M,Jacquier A,Liebminger E,Nobis B,Kappel L,van der Klei I,Högenauer G,Fromont-Racine M,Bergler H

    更新日期:2007-10-01 00:00:00

  • Dyskerin is a component of the Arabidopsis telomerase RNP required for telomere maintenance.

    abstract::Dyskerin binds the H/ACA box of human telomerase RNA and is a core telomerase subunit required for RNP biogenesis and enzyme function in vivo. Missense mutations in dyskerin result in dyskeratosis congenita, a complex syndrome characterized by bone marrow failure, telomerase enzyme deficiency, and progressive telomere...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kannan K,Nelson AD,Shippen DE

    更新日期:2008-04-01 00:00:00