Related Experiment Video
Updated: May 30, 2025

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Regulating Nrf2 activity: ubiquitin ligases and signaling molecules in redox homeostasis
John D Hayes1, Sharadha Dayalan Naidu1, Albena T Dinkova-Kostova1
1Jacqui Wood Cancer Centre, Division of Cancer Research, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK.
Abstract:
Transcription factor NF-E2 p45-related factor 2 (Nrf2) orchestrates defenses against oxidants and thiol-reactive electrophiles. It is controlled at the protein stability level by several E3 ubiquitin ligases (CRL3Keap1, CRL4DCAF11, SCFβ-TrCP, and Hrd1). CRL3Keap1 is of the greatest importance because it constitutively targets Nrf2 for proteasomal degradation under homeostatic conditions but is prevented from doing so by oxidative stressors. Repression of Nrf2 by CRL3Keap1 is attenuated by SQSTM1/p62, and this is reinforced by phosphorylation of SQSTM1/p62. Repression by SCFβ-TrCP requires phosphorylation of Nrf2 by GSK3, the activity of which is inhibited by PKB/Akt and other kinases. We discuss how Nrf2 activity is controlled by the ubiquitin ligases under different circumstances. We also describe endogenous signaling molecules that inactivate CRL3Keap1 to alleviate stress and restore homeostasis.
Related Concept Videos
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Regulation of the Unfolded Protein Response
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
The Unfolded Protein Response
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...

