PMID- 15476858
OWN - NLM
STAT- MEDLINE
DCOM- 20041130
LR  - 20240306
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 555
IP  - 1-2
DP  - 2004 Nov 2
TI  - Contribution of NAD(P)H:quinone oxidoreductase 1 to protection against 
      carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine 
      zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription 
      factors.
PG  - 149-71
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is a key enzyme involved in defence 
      against reactive forms of oxygen and inhibition of neoplasia. Under conditions of 
      oxidative stress, expression of NQO1 is induced, and the resulting increase in 
      oxidoreductase protein provides the cell with multiple layers of protection 
      against environmental insults. Firstly, the catalytic activity of NQO1 is 
      directed towards the complete reduction and detoxication of highly reactive 
      quinones. Secondly, the oxidoreductase maintains the endogenous lipid-soluble 
      antioxidants, alpha-tocopherol-hydroquinone and ubiquinol in their reduced and 
      active forms. Thirdly, NQO1 is required for the stabilisation of p53 protein in 
      response to DNA-damaging stimuli, and it thereby influences cell fate decisions. 
      In view of the anticarcinogenic actions of NQO1, an understanding of the 
      mechanisms that govern its expression is desirable. The redox sensitivity of NQO1 
      transcription occurs through a cis-acting antioxidant response element (ARE) 
      located within the regulatory region of the mouse, rat and human genes. This 
      element recruits the positively acting basic leucine zipper (bZip) transcription 
      factor NF-E2 p45-related factor 2 (Nrf2). Under normal constitutive conditions, 
      Nrf2 associates with the cytoskeletal-binding protein Keap1, which regulates the 
      subcellular distribution of the bZip factor and also targets it for 
      proteasome-dependent degradation. Oxidative stress inhibits the Nrf2-Keap1 
      interaction, thus promoting nuclear accumulation of the transcription factor and 
      transactivation of NQO1 and other ARE-driven genes. Mouse, rat and human NQO1 can 
      also be induced by planar aromatic hydrocarbons through a cis-acting xenobiotic 
      response element (XRE) located in their gene promoters. The XRE recruits the 
      arylhydrocarbon receptor (AhR) and AhR nuclear translocator. Cross-talk may occur 
      between Nrf2 and AhR, but the details of this process remain to be elucidated.
FAU - Nioi, Paul
AU  - Nioi P
AD  - Biomedical Research Centre, Ninewells Hospital and Medical School, University of 
      Dundee, Dundee DD1 9SY, Scotland, United Kingdom.
FAU - Hayes, John D
AU  - Hayes JD
LA  - eng
GR  - G0000281/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Antioxidants)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Quinones)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (NQO1 protein, human)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Base Sequence
MH  - DNA-Binding Proteins/*metabolism
MH  - *Gene Expression Regulation, Enzymologic
MH  - Helix-Loop-Helix Motifs/physiology
MH  - Humans
MH  - Leucine Zippers/physiology
MH  - Molecular Sequence Data
MH  - NAD(P)H Dehydrogenase (Quinone)/*physiology
MH  - NF-E2-Related Factor 2
MH  - Neoplasms/*prevention & control
MH  - Oxidation-Reduction
MH  - Quinones/metabolism
MH  - Receptors, Aryl Hydrocarbon/*metabolism
MH  - Response Elements/genetics
MH  - Signal Transduction
MH  - Trans-Activators/*metabolism/*physiology
MH  - Transcription Factors/physiology
RF  - 151
EDAT- 2004/10/13 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/10/13 09:00
PHST- 2004/03/08 00:00 [received]
PHST- 2004/05/14 00:00 [revised]
PHST- 2004/05/15 00:00 [accepted]
PHST- 2004/10/13 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/10/13 09:00 [entrez]
AID - S0027-5107(04)00289-1 [pii]
AID - 10.1016/j.mrfmmm.2004.05.023 [doi]
PST - ppublish
SO  - Mutat Res. 2004 Nov 2;555(1-2):149-71. doi: 10.1016/j.mrfmmm.2004.05.023.