Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2

Kool, Jaap; Hamdi, Mohamed; Cornelissen-Steijger, Paulien; Eb, A. J. Van Der; Terleth, Carrol; Dam, Hans van

doi:10.1038/sj.onc.1206611

Cited by 74 publications

(53 citation statements)

References 54 publications

(53 reference statements)

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“…31,32 Moreover, the observed upregulation of ATF3 is thought to slow down progression from G 1 to S phase but might also be involved in G 2 arrest after IR. 33,34 Furthermore, upregulation of PCNA in Reh cells may enhance DNA replication but was probably a result of IR induced DNA repair in our study. 35 Temporal expression profiles may give information about the onset of gene regulation in relation to when the phenotypic changes are detected.…”

Section: Discussionmentioning

confidence: 56%

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Lyng

Landsverk

Kristiansen

et al. 2005

Intl Journal of Cancer

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The human malignant B-lymphocyte cell lines Reh and U698 show arrest in G 2 phase after ionizing radiation (IR), but only Reh cells arrest in G 1 phase and die by apoptosis. We have used cDNA microarrays to measure changes in gene expression at 2, 4 and 6 hr after irradiation of Reh and U698 cells with 0.5 and 4 Gy in order to begin exploring the molecular mechanisms underlying the phenotypic changes. We also investigated whether gene expression changes could be caused by possible aberrations of genes, as measured by comparative genomic hybridization. Reh cells showed upregulation of CDKN1A that likely mediated the G 1 arrest. In contrast, U698 cells have impaired function of TP53 protein and no activation of CDKN1A, suppressing the arrest in G 1 . The G 2 arrest in both cell lines was likely due to repression of PLK1 and/or CCNF. IR-induced apoptosis in Reh cells was probably mediated by TP53 and CDKN1A, whereas a high expression level of MCL1, caused by gene amplification, and activation of the NFKB pathway may have suppressed the apoptotic response in U698 cells. Genes suggested to be involved in apoptosis were activated long before this phenotype was detectable and showed the same temporal expression profiles as genes involved in cell cycle arrest. Our results suggest that differences in functionality and/or copy number of several genes involved in IR-regulated pathways contributed to the phenotypic differences between Reh and U698 cells after IR, and that multiple molecular factors control the radiation response of malignant B lymphocytes. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 56%

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Lyng

Landsverk

Kristiansen

et al. 2005

Intl Journal of Cancer

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“…ATF3 is a member of the ATF/CREB family of transcription factors and was induced in response to various types of stress, including serum stimulation, inhibition of protein synthesis, ionizing radiation, and UV radiation (40), in part through the ERK, JNK, and p38 pathways (41,42), and was involved in cell growth and survival (31,43). However, ATF3 played no role in the survival of MEF cells at high temperature or in cell growth after a single exposure to high temperature, whereas HSF1 did (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

Heat Shock Transcription Factor 1 Inhibits Expression of IL-6 through Activating Transcription Factor 3

Takii

Inouye

Fujimoto

et al. 2009

The Journal of Immunology

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The febrile response is a complex physiological reaction to disease, including a cytokine-mediated increase in body temperature and the activation of inflammatory systems. Fever has beneficial roles in terms of disease prognosis, partly by suppressing the expression of inflammatory cytokines. However, the molecular mechanisms underlining the fever-mediated suppression of inflammatory gene expression have not been clarified. In this study, we showed that heat shock suppresses LPS-induced expression of IL-6, a major pyrogenic cytokine, in mouse embryonic fibroblasts and macrophages. Heat shock transcription factor 1 (HSF1) activated by heat shock induced the expression of activating transcription factor (ATF) 3, a negative regulator of IL-6, and ATF3 was necessary for heat-mediated suppression of IL-6, indicating a fever-mediated feedback loop consisting of HSF1 and ATF3. A comprehensive analysis of inflammatory gene expression revealed that heat pretreatment suppresses LPS-induced expression of most genes (86%), in part (67%) via ATF3. When HSF1-null and ATF3-null mice were injected with LPS, they expressed much higher levels of IL-6 than wild-type mice, resulting in an exaggerated febrile response. These results demonstrate a novel inhibitory pathway for inflammatory cytokines.

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“…Evidence supporting interactions between p53 and ATF3 proteins has led to the proposal that ATF3 can inhibit p53 transactivation capacity (31). ATF3 is induced in response to stress agents, such as UV and ionizing radiation (IR), not only via p53 but also by p53-independent pathways (32,33). Similar to p53, ATF3 expression is associated with cell cycle arrest and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Mutant p53 Protects Cells from 12-O-Tetradecanoylphorbol-13-Acetate–Induced Death by Attenuating Activating Transcription Factor 3 Induction

Buganim

Kalo²,

Brosh³

et al. 2006

Cancer Research

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Mutations in p53 are ubiquitous in human tumors. Some p53 mutations not only result in loss of wild-type (WT) activity but also grant additional functions, termed ''gain of function.'' In this study, we explore how the status of p53 affects the immediate response gene activating transcription factor 3 (ATF3) in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-protein kinase C (PKC) pathway. We show that high doses of TPA induce ATF3 in a WT p53-independent manner correlating with PKCs depletion and cell death. We show that cells harboring mutant p53 have attenuated ATF3 induction and are less sensitive to TPA-induced death compared with their p53-null counterparts. Mutagenesis analysis of the ATF3 promoter identified the regulatory motifs cyclic AMP-responsive element binding protein/ATF and MEF2 as being responsible for the TPA-induced activation of ATF3. Moreover, we show that mutant p53 attenuates ATF3 expression by two complementary mechanisms. It interacts with the ATF3 promoter and influences its activity via the MEF2 site, and additionally, it attenuates transcriptional expression of the ATF3 activator MEF2D.

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Induction of ATF3 by ionizing radiation is mediated via a signaling pathway that includes ATM, Nibrin1, stress-induced MAPkinases and ATF-2

Cited by 74 publications

References 54 publications

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Response of malignant B lymphocytes to ionizing radiation: Gene expression and genotype

Heat Shock Transcription Factor 1 Inhibits Expression of IL-6 through Activating Transcription Factor 3

Mutant p53 Protects Cells from 12-O-Tetradecanoylphorbol-13-Acetate–Induced Death by Attenuating Activating Transcription Factor 3 Induction

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