GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:24939851

From GONUTS
Jump to: navigation, search
Citation

Edagawa, M, Kawauchi, J, Hirata, M, Goshima, H, Inoue, M, Okamoto, T, Murakami, A, Maehara, Y and Kitajima, S (2014) 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. J. Biol. Chem. 289:21544-61

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 of ATF3 caused 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.

Links

PubMed PMC4118115 Online version:10.1074/jbc.M114.558890

Keywords

Activating Transcription Factor 3/genetics; Activating Transcription Factor 3/physiology; Apoptosis/drug effects; Apoptosis/physiology; Base Sequence; Celecoxib; Cell Line, Tumor; Colonic Neoplasms/pathology; DNA Primers; Endoplasmic Reticulum/physiology; Humans; Promoter Regions, Genetic; Pyrazoles/pharmacology; Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Sesquiterpenes/pharmacology; Sulfonamides/pharmacology; TNF-Related Apoptosis-Inducing Ligand/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ATF3

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:O14763)

Seeded From UniProt

complete

HUMAN:ATF3

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P35638

F

  • has_input:(UniProtKB:O14763)

Seeded From UniProt

complete

HUMAN:ATF3

involved_in

GO:1903984: positive regulation of TRAIL-activated apoptotic signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ATF3

involved_in

GO:1990440: positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ATF4

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_expression_of:(UniProtKB:P18847)
  • part_of:(GO:0034976)|regulates_expression_of(UniProtKB:P35638)
  • part_of:(GO:0034976)|regulates_expression_of(UniProtKB:O14763)
  • part_of:(GO:0034976)

Seeded From UniProt

complete

HUMAN:DDIT3

enables

GO:0000976: transcription cis-regulatory region binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:O14763)

Seeded From UniProt

complete

HUMAN:DDIT3

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P18847

F

  • has_input:(UniProtKB:O14763)

Seeded From UniProt

complete

HUMAN:DDIT3

involved_in

GO:1990440: positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:O14763)

Seeded From UniProt

complete

MOUSE:ATF3

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P02340

P

  • has_input:(UniProtKB:Q9QZM4)

Seeded From UniProt

complete

HUMAN:ATF4

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_expression_of:(ENSEMBL:ENSG00000162772)
  • part_of:(GO:0034976)|regulates_expression_of(ENSEMBL:ENSG00000175197)
  • part_of:(GO:0034976)|regulates_expression_of(ENSEMBL:ENSG00000120889)
  • part_of:(GO:0034976)

Seeded From UniProt

complete

HUMAN:ATF4

involved_in

GO:0034976: response to endoplasmic reticulum stress

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:DDIT3

enables

GO:0000976: transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

has_direct_input:(UniProtKB:O14763)

Seeded From UniProt

complete

HUMAN:DDIT3

enables

GO:0003700: DNA-binding transcription factor activity

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P18847

F

has_regulation_target:(UniProtKB:O14763)

Seeded From UniProt

complete

HUMAN:DDIT3

involved_in

GO:1990440: positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

ECO:0000314: direct assay evidence used in manual assertion

P

has_regulation_target:(UniProtKB:O14763)

Seeded From UniProt

complete

MOUSE:ATF3

involved_in

GO:0010628: positive regulation of gene expression

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P02340

P

has_regulation_target:(UniProtKB:Q9QZM4)

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.