PMID- 16008523
OWN - NLM
STAT- MEDLINE
DCOM- 20060221
LR  - 20181113
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 392
IP  - Pt 1
DP  - 2005 Nov 15
TI  - Arsenite induces a cell stress-response gene, RTP801, through reactive oxygen 
      species and transcription factors Elk-1 and CCAAT/enhancer-binding protein.
PG  - 93-102
AB  - RTP801 is a newly discovered stress-response gene that is induced by hypoxia and 
      other cell stress signals. Arsenic is a heavy metal that is linked to 
      carcinogenesis in humans. Here, we investigated the mechanism by which arsenic 
      induces RTP801 transcription. In HaCaT human keratinocytes, arsenite was able to 
      induce a rapid rise in the RTP801 mRNA level. Correspondingly, arsenite treatment 
      was capable of stimulating a 2.5 kb human RTP801 promoter. Such a stimulatory 
      effect was inhibited by co-expression of superoxide dismutase or glutathione 
      peroxidase, and was abrogated by N-acetylcysteine, implying that ROS (reactive 
      oxygen species) were involved in transcriptional regulation of the RTP801 gene. A 
      series of deletion studies with the promoter revealed a critical 
      arsenic-responsive region between -1057 and -981 bp of the promoter. Point 
      mutations of the putative Elk-1 site and the C/EBP (CCAAT/enhancer-binding 
      protein) site within this region were able to reduce the stimulatory effect of 
      arsenite, indicating that Elk-1 and C/EBP are involved in transcriptional 
      regulation of the RTP801 gene by arsenite. Furthermore, a gel mobility-shift 
      assay demonstrated that arsenite was able to mount the rapid formation of a 
      protein complex that bound the arsenic-responsive region as well as the 
      C/EBP-containing sequence. The arsenite stimulation on RTP801 transcription was 
      partly mediated by the ERK (extracellular-signal-regulated kinase) pathway, since 
      the effect of RTP801 was inhibited by a selective ERK inhibitor. In addition, 
      overexpression of Elk-1 and C/EBPbeta was able to elevate the promoter activity. 
      Therefore these studies indicate that RTP801 is a transcriptional target of 
      arsenic in human keratinocytes, and that arsenic and ROS production are linked to 
      Elk-1 and C/EBP in the transcriptional control.
FAU - Lin, Lin
AU  - Lin L
AD  - Department of Medical and Molecular Genetics, Walther Oncology Center, Indiana 
      University School of Medicine and the Walther Cancer Institute, Indianapolis, IN 
      46202, USA.
FAU - Stringfield, Teresa M
AU  - Stringfield TM
FAU - Shi, Xianglin
AU  - Shi X
FAU - Chen, Yan
AU  - Chen Y
LA  - eng
GR  - R01 DK055991/DK/NIDDK NIH HHS/United States
GR  - R01-DK55991/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Arsenites)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (DDIT4 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factors)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - N5509X556J (arsenite)
SB  - IM
MH  - Apoptosis
MH  - Arsenites/*pharmacology
MH  - Base Sequence
MH  - CCAAT-Enhancer-Binding Protein-beta/*metabolism
MH  - Cell Line
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - ets-Domain Protein Elk-1/*metabolism
PMC - PMC1317668
EDAT- 2005/07/13 09:00
MHDA- 2006/02/24 09:00
PMCR- 2006/05/15
CRDT- 2005/07/13 09:00
PHST- 2005/07/13 09:00 [pubmed]
PHST- 2006/02/24 09:00 [medline]
PHST- 2005/07/13 09:00 [entrez]
PHST- 2006/05/15 00:00 [pmc-release]
AID - BJ20050553 [pii]
AID - bj3920093 [pii]
AID - 10.1042/BJ20050553 [doi]
PST - ppublish
SO  - Biochem J. 2005 Nov 15;392(Pt 1):93-102. doi: 10.1042/BJ20050553.