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Toward clinical application of the Keap1-Nrf2 pathway

Journal

TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 34, Issue 6, Pages 340-346

Publisher

ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2013.04.005

Keywords

stress response; Cul3-based ubiquitin E3 ligase; cysteine code; two-site substrate recognition model; hinge and latch model

Funding

  1. Japan Society for the Promotion of Science (JSPS)
  2. Ministry of Education, Culture, Sports, Science, and Technology (MEXT)
  3. Tohoku University Global COE Program for Conquest of Signal Transduction Diseases with 'Network Medicine'
  4. CREST from Japan Science and Technology Agency (JST)
  5. NAITO foundation

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The Keap1-Nrf2 pathway plays a crucial role in determining the sensitivity of cells to chemical and/or oxidative insults by regulating the basal and inducible expression of detoxification and antioxidant enzymes, ABC transporters, and other stress response enzymes and/or proteins. Increasing attention has been focused on the roles that the Keap1-Nrf2 pathway plays in the protection of our body against drug toxicity and stress-induced diseases. Simultaneously, Nrf2 has been recognized to promote oncogenesis and resistance to chemotherapeutic drugs. Cancer cells hijack Nrf2 activity to support their malignant growth and thus Nrf2 has emerged as a therapeutic target. Translational studies of the Keap1-Nrf2 system, from mechanistic understanding to clinical applications, are now important to improve human health.

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