Answers are grounded in this paper and cite their sources.
Nrf2 is a transcription factor responsible for gene expression of a series of anti-oxidant proteins and detoxifying enzymes. Keap1, an adaptor protein of Cullin-3 ubiquitin ligase, senses electrophilic or oxidative stresses and then arrests ubiquitination of Nrf2, leading to Nrf2 activation. In addition to this canonical pathway, one Nrf2 target (p62/SQSTM1) competitively binds to Keap1 to activate Nrf2. The p62/SQSTM1-Keap1-Nrf2 axis is linked to selective autophagy and regulated by post-translational modifications such as sequential phosphorylation and ubiquitination of p62/SQSTM1. Importantly, this non-canonical pathway is hyper-activated in autophagy-deficient mouse livers and tissues of hepatocellular carcinoma. In this review, we delineate a molecular mechanism of Nrf2-activation by p62/SQSTM1, and describe its physiological role as well as the pathophysiological significance in autophagy-knockout livers and human hepatocellular carcinoma.
No takes yet. Share an insight, caveat, or question.
Katsuragi et al. (2016) studied this question.
Synapse has enriched 10 related papers. Consider them for comparative context: