PMID- 21927023
OWN - NLM
STAT- MEDLINE
DCOM- 20120629
LR  - 20131121
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 31
IP  - 17
DP  - 2012 Apr 26
TI  - Key role of ATF3 in p53-dependent DR5 induction upon DNA damage of human colon 
      cancer cells.
PG  - 2210-21
LID - 10.1038/onc.2011.397 [doi]
AB  - Stress response gene ATF3 is one of the p53 target genes and has a tumor 
      suppressor role in cancer. However, the biological role of p53-ATF3 pathway is 
      not well understood. Death receptor 5 (DR5) is a death domain-containing 
      transmembrane receptor that triggers cell death upon binding to its ligand TRAIL 
      (tumor necrosis factor-related apoptosis-inducing ligand), and a combination of 
      TRAIL and agents that increase the expression of DR5 is expected as a novel 
      anticancer therapy. In this report, we demonstrate that ATF3 is required for 
      efficient DR5 induction upon DNA damage by camptothecin (CPT) in colorectal 
      cancer cells. In the absence of ATF3, induction of DR5 messenger RNA and protein 
      is remarkably abrogated, and this is associated with reduced cell death by TRAIL 
      and CPT. By contrast, exogenous expression of ATF3 causes more rapid and elevated 
      expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by 
      TRAIL/CPT. Reporter assay and DNA affinity precipitation assay demonstrate that 
      at least three ATF/CRE motifs at the proximal promoter of the human DR5 gene are 
      involved in the activation of DNA damage-induced DR5 gene transcription. 
      Furthermore, ATF3 is shown to interact with p53 to form a complex on the DR5 gene 
      by Re-chromatin immunoprecipitation assay. Taken together, our results provide a 
      novel insight into the role of ATF3 as an essential co-transcription factor for 
      p53 upon DNA damage, and this may represent a useful biomarker for TRAIL-based 
      anticancer therapy.
FAU - Taketani, K
AU  - Taketani K
AD  - Department of Biochemical Genetics, Medical Research Institute, Tokyo Medical and 
      Dental University, Tokyo, Japan.
FAU - Kawauchi, J
AU  - Kawauchi J
FAU - Tanaka-Okamoto, M
AU  - Tanaka-Okamoto M
FAU - Ishizaki, H
AU  - Ishizaki H
FAU - Tanaka, Y
AU  - Tanaka Y
FAU - Sakai, T
AU  - Sakai T
FAU - Miyoshi, J
AU  - Miyoshi J
FAU - Maehara, Y
AU  - Maehara Y
FAU - Kitajima, S
AU  - Kitajima S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110919
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (ATF3 protein, human)
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Trans-Activators)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Activating Transcription Factor 3/genetics/*physiology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Camptothecin/pharmacology
MH  - Cell Line, Tumor
MH  - DNA Damage
MH  - Fibroblasts/metabolism
MH  - *Genes, p53
MH  - Humans
MH  - Mice
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/*metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/metabolism/pharmacology
MH  - Trans-Activators/metabolism
EDAT- 2011/09/20 06:00
MHDA- 2012/06/30 06:00
CRDT- 2011/09/20 06:00
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/06/30 06:00 [medline]
AID - onc2011397 [pii]
AID - 10.1038/onc.2011.397 [doi]
PST - ppublish
SO  - Oncogene. 2012 Apr 26;31(17):2210-21. doi: 10.1038/onc.2011.397. Epub 2011 Sep 
      19.