NBR1-mediated p62-liquid droplets enhance the Keap1-Nrf2 system

ABSTRACT: p62/SQSTM1 is a multivalent protein that has the ability to cause liquid-liquid phase separation and serves as a receptor protein that participates in cargo isolation during selective autophagy. This protein is also involved in the non-canonical activation of the Keap1-Nrf2 system, a major oxidative stress response pathway. Here, we show a role of Neighbor of BRCA1 gene 1 (NBR1), an autophagy receptor structurally similar to p62/SQSTM1, in p62-liquid droplet formation and Keap1-Nrf2 pathway activation. Overexpression of NBR1 blocks selective degradation of p62/SQSTM1 through autophagy and promotes the accumulation and phosphorylation of p62/SQSTM1 in liquid-like bodies, which is required for the activation of Nrf2. NBR1 is induced in response to oxidative stress, which trigegrs p62-mediate

SUBMITTER: Dr. Masaaki Komatsu 

PROVIDER: S-SCDT-EMBOR-2019-48902V1 | biostudies-other |

REPOSITORIES: biostudies-other