PAWH1 and PAWH2 are plant-specific components of an Arabidopsis endoplasmic reticulum-associated degradation complex

作者：Liangguang Leo Lin, Cong-Cong Zhang, Yongwu Chen, Yi Wang, Dinghe Wang, Xiaolei Liu, Muyang Wang, Juan Mao, Jianjun Zhang, Weiman Xing, Linchuan Liu, Jianming Li · 发表于：Nature Communications · 年份：2019 · DOI：10.1038/s41467-019-11480-7 · 被引用次数：50 · 研究领域：Endoplasmic Reticulum Stress and Disease、Autophagy in Disease and Therapy、Photosynthetic Processes and Mechanisms

Endoplasmic reticulum-associated degradation (ERAD) is a unique mechanism to degrade misfolded proteins via complexes containing several highly-conserved ER-anchored ubiquitin ligases such as HMG-CoA reductase degradation1 (Hrd1). Arabidopsis has a similar Hrd1-containing ERAD machinery; however, our knowledge of this complex is limited. Here we report two closely-related Arabidopsis proteins, Protein Associated With Hrd1-1 (PAWH1) and PAWH2, which share a conserved domain with yeast Altered Inheritance of Mitochondria24. PAWH1 and PAWH2 localize to the ER membrane and associate with Hrd1 via EMS-mutagenized Bri1 Suppressor7 (EBS7), a plant-specific component of the Hrd1 complex. Simultaneously elimination of two PAWHs constitutively activates the unfolded protein response and compromises stress tolerance. Importantly, the pawh1 pawh2 double mutation reduces the protein abundance of EBS7 and Hrd1 and inhibits degradation of several ERAD substrates. Our study not only discovers additional plant-specific components of the Arabidopsis Hrd1 complex but also reveals a distinct mechanism for regulating the Hrd1 stability.