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NBR1-mediated p62-liquid droplets enhance the Keap1-Nrf2 system.
EMBO Reports ( IF 6.5 ) Pub Date : 2020-01-09 , DOI: 10.15252/embr.201948902
Pablo Sánchez-Martín 1 , Yu-Shin Sou 2 , Shun Kageyama 1 , Masato Koike 2 , Satoshi Waguri 3 , Masaaki Komatsu 1
Affiliation  

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 triggers p62-mediated Nrf2 activation. Conversely, loss of Nbr1 suppresses not only the formation of p62/SQSTM1-liquid droplets, but also of p62-dependent Nrf2 activation during oxidative stress. Taken together, our results show that NBR1 mediates p62/SQSTM1-liquid droplet formation to activate the Keap1-Nrf2 pathway.

中文翻译:

NBR1 介导的 p62 液滴增强了 Keap1-Nrf2 系统。

p62/SQSTM1 是一种多价蛋白,具有引起液-液相分离的能力,并作为受体蛋白参与选择性自噬过程中的货物分离。该蛋白质还参与 Keap1-Nrf2 系统的非规范激活,这是一种主要的氧化应激反应途径。在这里,我们展示了 BRCA1 基因 1 (NBR1) 的邻居在 p62 液滴形成和 Keap1-Nrf2 通路激活中的作用,这是一种结构上类似于 p62/SQSTM1 的自噬受体。NBR1 的过表达通过自噬阻断 p62/SQSTM1 的选择性降解,并促进 p62/SQSTM1 在液体样体中的积累和磷酸化,这是激活 Nrf2 所必需的。NBR1 响应于氧化应激而被诱导,氧化应激触发 p62 介导的 Nrf2 激活。反过来,Nbr1 的缺失不仅抑制了 p62/SQSTM1 液滴的形成,而且还抑制了氧化应激过程中 p62 依赖性 Nrf2 的激活。总之,我们的结果表明 NBR1 介导 p62/SQSTM1-液滴形成以激活 Keap1-Nrf2 通路。
更新日期:2020-03-04
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