title: The ubiquitin-like domain of Herp is involved in Herp degradation, but not necessary for its enhancement of amyloid beta-protein generation.
abstract: 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 beta-protein (Abeta) and that Herp interacts with presenilin (PS). Here, we addressed the role of the ULD of Herp in Abeta generation and intracellular Herp stability. We found that the ULD is not essential for the enhancement of Abeta 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.
authors.affiliation: Department of Dementia Research, National Institute for Longevity Sciences, Obu, Aichi, Japan.
authors.forename: Xiaorei
authors.initials: X
authors.lastname: Sai
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Shiraishi
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: Hiroto
authors.initials: H
authors.lastname: Komano
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C485932:HERPUD1 protein, human; C415829:Herpud1 protein, mouse; D008565:Membrane Proteins; D010446:Peptide Fragments; D025801:Ubiquitin; C067713:lactacystin; D000111:Acetylcysteine