Site-directed mutagenesis of cysteine to serine in the DNA binding region of Nrf2 decreases its capacity to upregulate antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 geneDavid Bloom
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, TX 77030, USA
Oncogene 21:2191-200. 2002
..Therefore, the C506S mutation in Nrf2 lowered its affinity for the ARE, leading to decreased expression, and antioxidant induction, of NQO1...
- Phosphorylation of Nrf2 at Ser40 by protein kinase C in response to antioxidants leads to the release of Nrf2 from INrf2, but is not required for Nrf2 stabilization/accumulation in the nucleus and transcriptional activation of antioxidant response element
David A Bloom
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 278:44675-82. 2003
..A peptide that competes with endogenous Nrf2 for INrf2 binding was able to induce ARE activity more effectively than t-butylhydroquinone, and Nrf2 that accumulated in the nucleus as a result was not phosphorylated...
- Nrf2 signaling in coordinated activation of antioxidant gene expression
Anil K Jaiswal
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Free Radic Biol Med 36:1199-207. 2004
..The future studies should also reveal a complete mechanism of signal transduction from antioxidants and xenobiotics to the transcription factors, such as Nrf2, that bind to ARE...
- Bach1 competes with Nrf2 leading to negative regulation of the antioxidant response element (ARE)-mediated NAD(P)H:quinone oxidoreductase 1 gene expression and induction in response to antioxidants
Saravanakumar Dhakshinamoorthy
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 280:16891-900. 2005
..The results further suggest that antioxidant-induced delayed accumulation of Bach1 contributes to the down-regulation of ARE-regulated genes, presumably to reduce the antioxidant enzymes to normal levels...
- Nuclear import and export signals in control of Nrf2
Abhinav K Jain
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
J Biol Chem 280:29158-68. 2005
..Antioxidants change this balance in favor of nuclear accumulation of Nrf2, leading to activation of chemopreventive proteins. Once this is achieved, Nrf2 exits the nucleus for binding to INrf2 and degradation...
- Deficiency of NRH:quinone oxidoreductase 2 differentially regulates TNF signaling in keratinocytes: up-regulation of apoptosis correlates with down-regulation of cell survival kinases
Kwang Seok Ahn
Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Cancer Res 67:10004-11. 2007
..Overall, our results indicate that deletion of NQO2 plays a differential role in TNF signaling pathway: by suppressing cell survival signals and potentiating TNF-induced apoptosis...
- NRH:quinone oxidoreductase 2 (NQO2) catalyzes metabolic activation of quinones and anti-tumor drugs
Claudia M Celli
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Biochem Pharmacol 72:366-76. 2006
..These results concluded that NQO2 plays a significant role in the metabolic activation of both quinones and anti-tumor drugs leading to cytotoxicity and cell death...
- Nuclear factor Nrf2 and antioxidant response element regulate NRH:quinone oxidoreductase 2 (NQO2) gene expression and antioxidant induction
Wei Wang
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Free Radic Biol Med 40:1119-30. 2006
..The results combined demonstrated that Nrf2 associates with JunD, binds to ARE at nucleotide -1433, and regulates human NQO2 gene expression and induction in response to antioxidants...
- Thioredoxin-like domains required for glucose regulatory protein 58 mediated reductive activation of mitomycin C leading to DNA cross-linking
Anbu Karani Adikesavan
Department of Pharmacology, Baylor College of Medicine, Houston, Texas, USA
Mol Cancer Ther 6:2719-27. 2007
..These results led to conclusion that GRP58, through its two thioredoxin-like domains, functions as a reductase leading to bioreductive drug MMC activation and DNA cross-linking...
- Sp3 repression of polymorphic human NRH:quinone oxidoreductase 2 gene promoter
Wei Wang
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Free Radic Biol Med 37:1231-43. 2004
..These studies also suggest that alterations in NQO2 activity might be an important factor in susceptibility to Parkinson's disease...
- An auto-regulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance
Ok Hee Lee
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 282:36412-20. 2007
..The induction of INrf2 followed ubiquitination and degradation of Nrf2 and suppression of INrf2 gene expression. In conclusion, Nrf2 regulates INrf2 by controlling its transcription, and INrf2 controls Nrf2 by degrading it...
- Lower induction of p53 and decreased apoptosis in NQO1-null mice lead to increased sensitivity to chemical-induced skin carcinogenesis
Karim Iskander
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA
Cancer Res 65:2054-8. 2005
....
- Association of NRH:quinone oxidoreductase 2 gene promoter polymorphism with higher gene expression and increased susceptibility to Parkinson's disease
Wei Wang
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
J Gerontol A Biol Sci Med Sci 63:127-34. 2008
..The results suggest that the association of the D promoter with Parkinson's disease may be due to an increase in expression of the NQO2 gene...
- Regulation of antioxidant response element-dependent induction of detoxifying enzyme synthesis
Anil K Jaiswal
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
Methods Enzymol 378:221-38. 2004
- BALT development and augmentation of hyperoxic lung injury in mice deficient in NQO1 and NQO2
Amitava Das
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Free Radic Biol Med 40:1843-56. 2006
..These results suggest that NQO1 and NQO2 combined protect mice against lung inflammation, BALT, and hyperoxic lung injury...
- Low and high dose UVB regulation of transcription factor NF-E2-related factor 2
Sankaranarayanan Kannan
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Cancer Res 66:8421-9. 2006
..This resulted in nuclear exclusion of Nrf2 and down-regulation of ARE-mediated chemoprotective gene expression...
- In vivo role of NAD(P)H:quinone oxidoreductase 1 in metabolic activation of mitomycin C and bone marrow cytotoxicity
Anbu Karani Adikesavan
Department of Pharmacology, Baylor College of Medicine and Department of Pathology, Methodist Hospital, Houston, TX, USA
Cancer Res 67:7966-71. 2007
..NQO1(+/-) mice also showed limited resistance to mitomycin C-induced bone marrow cytotoxicity. These data show a major in vivo role of NQO1 in metabolic activation of mitomycin C with implications in mitomycin C chemotherapy...
- Nrf3 negatively regulates antioxidant-response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene
Kannan Sankaranarayanan
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 279:50810-7. 2004
..These results combined suggest that Nrf3 is a negative regulator of ARE-mediated gene expression...
- NQO1 and NQO2 regulation of humoral immunity and autoimmunity
Karim Iskander
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 281:30917-24. 2006
..The results led to the conclusion that NQO1 and NQO2 are endogenous factors in the regulation of immune response and autoimmunity...
Disruption of NAD(P)H:quinone oxidoreductase 1 gene in mice leads to radiation-induced myeloproliferative diseaseKarim Iskander
Department of Pharmacology, Baylor College of Medicine, Houston, Texas, USA
Cancer Res 68:7915-22. 2008
..1 and C/EBPalpha led to myeloid hyperplasia in NQO1(-/-) mice. The lack of induction of apoptosis and differentiation contributed to radiation-induced myeloproliferative disease in NQO1(-/-) mice...
- Quinone oxidoreductases in protection against myelogenous hyperplasia and benzene toxicity
Karim Iskander
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Chem Biol Interact 153:147-57. 2005
..Decreased apoptosis contributed to myelogenous hyperplasia. The studies on short-term exposure of NQO1-/- mice to benzene demonstrated substantially greater benzene-induced toxicity, as compared to wild type mice...
- Nrf2 signaling and cell survival
Suryakant K Niture
Department of Pharmacology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA
Toxicol Appl Pharmacol 244:37-42. 2010
....
- NRH:quinone oxidoreductase 2 and NAD(P)H:quinone oxidoreductase 1 protect tumor suppressor p53 against 20s proteasomal degradation leading to stabilization and activation of p53
Xing Gong
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
Cancer Res 67:5380-8. 2007
..These results suggest that stress-induced NQO1 and NQO2 transiently stabilize p53, which leads to protection against adverse effects of stressors...
- Si RNA inhibition of GRP58 associated with decrease in mitomycin C-induced DNA cross-linking and cytotoxicity
Shibing Su
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Chem Biol Interact 162:81-7. 2006
..These results suggest that GRP58 might be an important target enzyme for further studies on mitomycin C and similar drug therapy...
- Phosphorylation of tyrosine 568 controls nuclear export of Nrf2
Abhinav K Jain
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 281:12132-42. 2006
..Further experiments with small interfering RNA revealed that Fyn phosphorylated Nrf 2Y568 leading to nuclear export and degradation of Nrf 2...
Persistent induction of hepatic and pulmonary phase II enzymes by 3-methylcholanthrene in ratsSudha R Kondraganti
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030
Toxicol Sci 102:337-44. 2008
....
- NRH:quinone oxidoreductase 2-deficient mice are highly susceptible to radiation-induced B-cell lymphomas
Karim Iskander
Department of Pharmacology, Baylor College of Medicine, and Department of Pathology, Methodist Hospital, Houston, TX, USA
Clin Cancer Res 15:1534-42. 2009
..However, the role of NQO2 in prevention of hematologic malignancies remains unknown. Present studies investigated in vivo role of NQO2 in prevention of myeloproliferative disease and lymphomas...
- GSK-3beta acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2
Abhinav K Jain
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 282:16502-10. 2007
..The activated GSK-3beta phosphorylates Fyn at threonine residue(s). Phosphorylated Fyn accumulates in the nucleus and phosphorylates Nrf2 at tyrosine 568. This leads to nuclear export, ubiquitination, and degradation of Nrf2...
- Deficiency of NRH:quinone oxidoreductase 2 increases susceptibility to 7,12-dimethylbenz(a)anthracene and benzo(a)pyrene-induced skin carcinogenesis
Karim Iskander
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
Cancer Res 64:5925-8. 2004
..The results also suggest that lack of induction of p53, p21, and Bax proteins might contribute to increased sensitivity of NQO2-/- mice skin to benzo(a)pyrene carcinogenicity...
- c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and anti-oxidant induction
Saravanakumar Dhakshinamoorthy
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, TX 77030, USA
Oncogene 21:5301-12. 2002
..It reached a plateau at 4 h after t-BHQ treatment. The results together led to the conclusion that c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and induction in response to anti-oxidants...
- Nrf2:INrf2 (Keap1) signaling in oxidative stress
James W Kaspar
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Free Radic Biol Med 47:1304-9. 2009
..The switching on and off of Nrf2 protects cells against free radical damage, prevents apoptosis, and promotes cell survival...
- Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity
Delwin J Long
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
J Biol Chem 277:46131-9. 2002
..The NQO2-null mice are a model for NQO2 deficiency in humans and can be used to determine the role of this enzyme in sensitivities to toxicity and carcinogenesis...
- Genetic deletion of NAD(P)H:quinone oxidoreductase 1 abrogates activation of nuclear factor-kappaB, IkappaBalpha kinase, c-Jun N-terminal kinase, Akt, p38, and p44/42 mitogen-activated protein kinases and potentiates apoptosis
Kwang Seok Ahn
Cytokine Research Laboratory, Department of Experimental Therapeutics, M D Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA
J Biol Chem 281:19798-808. 2006
....
- Presence and induction of the enzyme NAD(P)H: quinone oxidoreductase 1 in the central nervous system
Janet L Stringer
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030 3498, USA
J Comp Neurol 471:289-97. 2004
..These results suggest that NQO1 has a role in myelination in the central nervous system or in the insulating/wrapping function of glial cells...
- Overlapping signal sequences control nuclear localization and endoplasmic reticulum retention of GRP58
Anbu Karani Adikesavan
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Biochem Biophys Res Commun 377:407-12. 2008
..These results concluded that overlapping NLS and ER retention signal sequences regulate nuclear localization and ER retention of GRP58...
- Quinone oxidoreductases and vitamin K metabolism
Xing Gong
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Vitam Horm 78:85-101. 2008
..Future studies are also required to identify the enzymes that catalyze high affinity reduction of vitamin K1 and K2 to hydroquinone for use in gamma-carboxylation reactions...
- Role of GRP58 in mitomycin C-induced DNA cross-linking
Claudia M Celli
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA
Cancer Res 63:6016-25. 2003
..Expression analysis using matched human tumor/normal array revealed an up-regulation of GRP58 in breast, uterus, lung, and stomach tumors compared with normal tissues of similar origin...
- Disruption of the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene in mice causes myelogenous hyperplasia
Delwin J Long
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Cancer Res 62:3030-6. 2002
....
- Laminar flow induction of antioxidant response element-mediated genes in endothelial cells. A novel anti-inflammatory mechanism
Xi Lin Chen
Discovery Research, AtheroGenics, Inc, Alpharetta, Georgia 30004, USA
J Biol Chem 278:703-11. 2003
..Furthermore, laminar flow activation of antioxidant genes via an ARE-dependent transcriptional mechanism may represent a novel athero-protective and anti-inflammatory mechanism in the vasculature...
- Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid
Jung H Suh
Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
Proc Natl Acad Sci U S A 101:3381-6. 2004
..Thus, the age-related loss in GSH synthesis may be caused by dysregulation of ARE-mediated gene expression, but chemoprotective agents, like LA, can attenuate this loss...
- BRCA1 induces antioxidant gene expression and resistance to oxidative stress
Insoo Bae
Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20057 1469, USA
Cancer Res 64:7893-909. 2004
..These findings suggest a novel function for BRCA1, i.e., to protect cells against oxidative stress. This function would be consistent with the postulated role of BRCA1 as a caretaker gene in preserving genomic integrity...
- Phosphorylation and dephosphorylation of tyrosine 141 regulate stability and degradation of INrf2: a novel mechanism in Nrf2 activation
Abhinav K Jain
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
J Biol Chem 283:17712-20. 2008
..This resulted in stabilization of Nrf2 and activation of ARE-mediated gene expression. These results demonstrate that stress-induced dephosphorylation of tyrosine 141 is a novel mechanism in Nrf2 activation and cellular protection...
