Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy.

ABSTRACT:

Background

Macro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure.

Results

In this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpress

SUBMITTER: Xia Q 

PROVIDER: S-EPMC9945626 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature