Role of Activating Transcription Factor 3 (ATF3) in Endoplasmic Reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of Death Receptor 5 (DR5) by zerumbone and celecoxib

Makoto Edagawa, Junya Kawauchi, Manabu Hirata, Hiroto Goshima, Makoto Inoue, Tatsuro Okamoto, Akira Murakami, Yoshihiko Maehara, Shigetaka Kitajima

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Death receptor 5 (DR5) is a death domain-containing transmembrane receptor that triggers cell death upon binding to its ligand, TNF-related apoptosis-inducing ligand (TRAIL), and a combination of TRAIL and agents that increase the expression of DR5 is expected to be a novel anticancer therapy. In this report, we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells. Both agents activated PERK-eIF2α kinases and induced the expression of activating transcription factor 4 (ATF4)-CCAAT enhancer-binding protein (C/EBP) homologous protein, which were remarkably suppressed by reactive oxygen species scavengers. In the absence of ATF3, the induction of DR5 mRNA and protein was abrogated significantly, and this was associated with reduced cell death by cotreatment of TRAIL with ZER or CCB. By contrast, exogenous expression ofATF3caused a more rapid and elevated expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by TRAIL/ZER or TRAIL/CCB. A reporter assay demonstrated that at least two ATF/cAMP response element motifs as well as C/EBP homologous protein motif at the proximal region of the human DR5 gene promoter were required for ZER-induced DR5 gene transcription. Taken together, our results provide novel insights into the role of ATF3 as an essential transcription factor for p53-independent DR5 induction upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL-based anticancer therapy.

Original languageEnglish
Pages (from-to)21544-21561
Number of pages18
JournalJournal of Biological Chemistry
Volume289
Issue number31
DOIs
Publication statusPublished - Aug 1 2014

Fingerprint

Celecoxib
Activating Transcription Factor 3
TNF-Related Apoptosis-Inducing Ligand Receptors
Endoplasmic Reticulum Stress
Colonic Neoplasms
TNF-Related Apoptosis-Inducing Ligand
Up-Regulation
Tumor Necrosis Factor-alpha
Cells
Apoptosis
Ligands
Cell death
CCAAT-Enhancer-Binding Proteins
Cell Death
Genes
Activating Transcription Factor 4
Amino Acid Motifs
Proteins
zerumbone
Response Elements

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Role of Activating Transcription Factor 3 (ATF3) in Endoplasmic Reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of Death Receptor 5 (DR5) by zerumbone and celecoxib. / Edagawa, Makoto; Kawauchi, Junya; Hirata, Manabu; Goshima, Hiroto; Inoue, Makoto; Okamoto, Tatsuro; Murakami, Akira; Maehara, Yoshihiko; Kitajima, Shigetaka.

In: Journal of Biological Chemistry, Vol. 289, No. 31, 01.08.2014, p. 21544-21561.

Research output: Contribution to journalArticle

@article{6a8385a0ca1c42feb6a8bead96a85b4e,
title = "Role of Activating Transcription Factor 3 (ATF3) in Endoplasmic Reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of Death Receptor 5 (DR5) by zerumbone and celecoxib",
abstract = "Death receptor 5 (DR5) is a death domain-containing transmembrane receptor that triggers cell death upon binding to its ligand, TNF-related apoptosis-inducing ligand (TRAIL), and a combination of TRAIL and agents that increase the expression of DR5 is expected to be a novel anticancer therapy. In this report, we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells. Both agents activated PERK-eIF2α kinases and induced the expression of activating transcription factor 4 (ATF4)-CCAAT enhancer-binding protein (C/EBP) homologous protein, which were remarkably suppressed by reactive oxygen species scavengers. In the absence of ATF3, the induction of DR5 mRNA and protein was abrogated significantly, and this was associated with reduced cell death by cotreatment of TRAIL with ZER or CCB. By contrast, exogenous expression ofATF3caused a more rapid and elevated expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by TRAIL/ZER or TRAIL/CCB. A reporter assay demonstrated that at least two ATF/cAMP response element motifs as well as C/EBP homologous protein motif at the proximal region of the human DR5 gene promoter were required for ZER-induced DR5 gene transcription. Taken together, our results provide novel insights into the role of ATF3 as an essential transcription factor for p53-independent DR5 induction upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL-based anticancer therapy.",
author = "Makoto Edagawa and Junya Kawauchi and Manabu Hirata and Hiroto Goshima and Makoto Inoue and Tatsuro Okamoto and Akira Murakami and Yoshihiko Maehara and Shigetaka Kitajima",
year = "2014",
month = "8",
day = "1",
doi = "10.1074/jbc.M114.558890",
language = "English",
volume = "289",
pages = "21544--21561",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "31",

}

TY - JOUR

T1 - Role of Activating Transcription Factor 3 (ATF3) in Endoplasmic Reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of Death Receptor 5 (DR5) by zerumbone and celecoxib

AU - Edagawa, Makoto

AU - Kawauchi, Junya

AU - Hirata, Manabu

AU - Goshima, Hiroto

AU - Inoue, Makoto

AU - Okamoto, Tatsuro

AU - Murakami, Akira

AU - Maehara, Yoshihiko

AU - Kitajima, Shigetaka

PY - 2014/8/1

Y1 - 2014/8/1

N2 - Death receptor 5 (DR5) is a death domain-containing transmembrane receptor that triggers cell death upon binding to its ligand, TNF-related apoptosis-inducing ligand (TRAIL), and a combination of TRAIL and agents that increase the expression of DR5 is expected to be a novel anticancer therapy. In this report, we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells. Both agents activated PERK-eIF2α kinases and induced the expression of activating transcription factor 4 (ATF4)-CCAAT enhancer-binding protein (C/EBP) homologous protein, which were remarkably suppressed by reactive oxygen species scavengers. In the absence of ATF3, the induction of DR5 mRNA and protein was abrogated significantly, and this was associated with reduced cell death by cotreatment of TRAIL with ZER or CCB. By contrast, exogenous expression ofATF3caused a more rapid and elevated expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by TRAIL/ZER or TRAIL/CCB. A reporter assay demonstrated that at least two ATF/cAMP response element motifs as well as C/EBP homologous protein motif at the proximal region of the human DR5 gene promoter were required for ZER-induced DR5 gene transcription. Taken together, our results provide novel insights into the role of ATF3 as an essential transcription factor for p53-independent DR5 induction upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL-based anticancer therapy.

AB - Death receptor 5 (DR5) is a death domain-containing transmembrane receptor that triggers cell death upon binding to its ligand, TNF-related apoptosis-inducing ligand (TRAIL), and a combination of TRAIL and agents that increase the expression of DR5 is expected to be a novel anticancer therapy. In this report, we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells. Both agents activated PERK-eIF2α kinases and induced the expression of activating transcription factor 4 (ATF4)-CCAAT enhancer-binding protein (C/EBP) homologous protein, which were remarkably suppressed by reactive oxygen species scavengers. In the absence of ATF3, the induction of DR5 mRNA and protein was abrogated significantly, and this was associated with reduced cell death by cotreatment of TRAIL with ZER or CCB. By contrast, exogenous expression ofATF3caused a more rapid and elevated expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by TRAIL/ZER or TRAIL/CCB. A reporter assay demonstrated that at least two ATF/cAMP response element motifs as well as C/EBP homologous protein motif at the proximal region of the human DR5 gene promoter were required for ZER-induced DR5 gene transcription. Taken together, our results provide novel insights into the role of ATF3 as an essential transcription factor for p53-independent DR5 induction upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL-based anticancer therapy.

UR - http://www.scopus.com/inward/record.url?scp=84905392984&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84905392984&partnerID=8YFLogxK

U2 - 10.1074/jbc.M114.558890

DO - 10.1074/jbc.M114.558890

M3 - Article

C2 - 24939851

AN - SCOPUS:84905392984

VL - 289

SP - 21544

EP - 21561

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 31

ER -