2007, Number 1
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Rev Educ Bioquimica 2007; 26 (1)
Nrf2: La historia de un nuevo factor de transcripción que responde a estrés oxidativo
Königsberg FM
Language: Spanish
References: 16
Page: 18-25
PDF size: 277.49 Kb.
ABSTRACT
The transcription factor Nrf2 regulates the inducible
expression of numerous detoxifying and antioxidant
genes. It binds to a specific DNA sequence known
as ARE (
Antioxidant
Response
Element), that can
be activated by several electrophils and oxidant
compounds of diverse chemical nature. Nrf2
activation is constitutively repressed by its binding
with a citosolic protein known as Keap1 and to the
citoskeleton. This interaction promotes the
permanent Nrf2 degradation by the proteosome,
implying that the primary control of Nrf2 function
lies on its subcellular distribution rather on its de
novo synthesis. It has been suggested that the Nrf2-
Keap1 system contributes to protection against
various pathologies, like cancer, liver toxicity and
inflammation.
REFERENCES
Sies H, Cárdenas E (1985) Oxidative stress: damage to intact cells and organs. Philos Trans R Soc Lond B Biol Sci 311:617-631.
Kobayashi A, Yamamoto M (2006) Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species. Advan Enzyme Regul 46: 113-140.
Lee JM, Johnson JA (2004) An important role of Nrf2- ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 37:139-143.
Lee JS, Surh YJ (2005) Nrf2 as a novel molecular target for chemoprevention. Cancer Lett 224:171-184.
Chan JY, Han XL, Kan YW (1993) Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc Natl Acad Sci USA 90:11371-11375.
Moi P, Chan K, Asunis I, Cao A, Kan YW (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci USA 91:9926-9930.
Venugopal R, Jaiswal AK (1996) Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene. Proc Natl Acad Sci USA 93:14960-14965.
Jaiswal AK (2004) Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med 36:1199-1207.
Kobayashi A, Kang M, Watai Y, Tong KI, Shibata T, Uchida K, Yamamoto M (2006) Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of keap. Mol Cel Biol 26:221-229.
Kensler TW, Wakabayashi N, Visual S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmocol Toxicol 47:6.1-6.28.
Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13:76-86.
Tong KI, Kobayashi A, Katsuoka F, Yamamoto M (2006) Two-site substrate recognition model for the Keap1-Nrf2 system: a hinge and latch mechanism. J Biol Chem 387:1311-1320.
Cullinan SB, Gordan JD, Jianping J, Harper JW, Diehl JA (2004) The Keap1-BTB Protein Is an Adaptor That Bridges Nrf2 to a Cul3-Based E3 Ligase: Oxidative Stress Sensing by a Cul3-Keap1 Ligase. Mol Cell Biol 24: 8477- 8486.
Itoh K, Tong KI, Yamamoto M (2004) Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med 36:1208-1213.
Dhakshinamoorthy S, Jaiswal AK (2000) Small Maf (MafG and MafK) Proteins negatively regulate antioxidant response element mediated expression and antioxidante induction of the NAD(P)H:Quinoone oxidoreductase gene. J Biol Chem 275:40134-40141.
Kapiszewska M (2006) A vegetable to meat consumption ratio as a relevant factor determining cancer preventive diet. En: Local Mediterranean Food Plants and Nutraceuticals. Editores: Heinrich M, Müller WE, Galli C. Ed. Karger, vol 59:130-153.