Role of Herp in the endoplasmic reticulum stress response.
Application of differential display to cultured rat astrocytes allowed cloning of Herp cDNA. Although Herp was strongly induced by endoplasmic reticulum (ER) stress, it decayed rapidly consequent to proteasome-mediated degradation. To investigate the role of this molecule in terms of the stress response, Herp knockout cells were developed using F9 embryonic carcinoma cells. F9 Herp null cells were more vulnerable to ER stress compared with F9 wild-type cells. In the early period of ER stress (0-8 h after tunicamycin treatment), Herp null cells displayed enhanced ER stress signalling and stabilization of an endogenous ERAD substrate, compared with wild-type cells. In the intermediate period (8-20 h after tunicamycin treatment), Herp null cells displayed reduced ER stress signalling, whereas in the late period (20-40 h after tunicamycin treatment), Herp null cells manifested irreversible cellular changes that lead to apoptotic cell death. Transfection analysis revealed that the N-terminal region, including the ubiquitin-like domain of Herp, was required for the survival of F9 cells under ER stress. These results indicate that Herp is a short-lived Ub-like protein improving the balance of folding capacity and protein loads in the ER and plays crucial roles for the ER stress resistance in F9 cells.
Hori
Osamu
O
Department of Neuroanatomy (Anatomy III), Kanazawa University Graduate School of Medicine, Kanazawa City, Ishikawa 920-8640, Japan. osamuh@nanat.m.kanazawa-u.ac.jp
Ichinoda
Fusae
F
Yamaguchi
Atsushi
A
Tamatani
Takashi
T
Taniguchi
Manabu
M
Koyama
Yoshihisa
Y
Katayama
Taiichi
T
Tohyama
Masaya
M
Stern
David M
DM
Ozawa
Kentaro
K
Kitao
Yasuko
Y
Ogawa
Satoshi
S
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016923:Cell Death; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
C485932:HERPUD1 protein, human; C415829:Herpud1 protein, mouse; D008565:Membrane Proteins