The ubiquitin-like domain of Herp is involved in Herp degradation, but not necessary for its enhancement of amyloid β-protein generation

Herp is an endoplasmic reticulum (ER)-stress-inducible membrane protein, which has a ubiquitin-like domain (ULD). However, its biological function is as yet unknown. Previously, we reported that a high expression level of Herp in cells increases the generation of amyloid β-protein (Aβ) and that Herp interacts with presenilin (PS). Here, we addressed the role of the ULD of Herp in Aβ generation and intracellular Herp stability. We found that the ULD is not essential for the enhancement of Aβ generation by Herp expression and the interaction of Herp with PS, but is involved in the rapid degradation of Herp, most likely via the ubiquitin/proteasome pathway. Thus, the ULD of Herp most likely plays a role in the regulation of the intracellular level of Herp under ER stress.