Maeda Tomoji, Fujita Yu, Tanabe-Fujimura Chiaki, Zou Kun, Liu Junjun, Liu Shuyu, Kikuchi Kota, Shen Xuefeng, Nakajima Toshihiro, Komano Hiroto
Department of Neuroscience, School of Pharmacy, Iwate Medical University.
Institute of Medical Science, Tokyo Medical University.
Biol Pharm Bull. 2018;41(6):915-919. doi: 10.1248/bpb.b18-00015.
Homocysteine-inducible endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible membrane protein involved in ER-associated degradation. Herp expression is maintained at low levels through a strict regulatory mechanism, but the details of this mechanism and the reasons why Herp expression is restricted in this manner remain unclear. Here, we show that Herp degradation involves synoviolin, an ER-resident E3 ubiquitin ligase. Herp protein levels were found to be markedly elevated in synoviolin-null cells, and Herp expression decreased when synoviolin was overexpressed. However, the lysine residues of Herp, which are ubiquitinated by E3 ubiquitin ligase, were not sufficient for regulation of Herp degradation. These results suggest that Herp degradation is mediated via synoviolin and that Herp ubiquitination involves amino acids other than lysine.
同型半胱氨酸诱导的内质网（ER）蛋白（Herp）是一种内质网应激诱导的膜蛋白，参与内质网相关降解。Herp的表达通过严格的调控机制维持在低水平，但该机制的细节以及Herp以这种方式受到限制的原因仍不清楚。在这里，我们表明Herp的降解涉及滑膜素，一种内质网驻留的E3泛素连接酶。发现在滑膜素缺失的细胞中Herp蛋白水平显著升高，而当滑膜素过表达时Herp表达下降。然而，被E3泛素连接酶泛素化的Herp赖氨酸残基不足以调节Herp的降解。这些结果表明Herp的降解是通过滑膜素介导的，并且Herp的泛素化涉及赖氨酸以外的氨基酸。
