title: Ubiquitin ligase Kf-1 is involved in the endoplasmic reticulum-associated degradation pathway.
abstract: Kf-1 was first identified as a gene showing enhanced expression in the cerebral cortex of a sporadic Alzheimer's disease patient. To date, however, the functional properties of Kf-1 protein remain unknown. In this study, immunohistochemical analysis showed that Kf-1 immunoreactivity was detected in rat hippocampus and cerebral cortex neurons. Interestingly, it was colocalized with endoplasmic reticulum (ER) marker. To investigate the specific function of Kf-1 protein, we generated Myc tagged wild type Kf-1 (Myc-Kf-1WT) and RING finger domain deletion mutant of Kf-1 (Myc-Kf-1DeltaR), and then transfected in HEK293 cells. Myc-Kf-1WT displayed a reticular pattern typical of ER localization, with large perinuclear aggregates and colocalized with ER marker, calnexin. Myc-Kf-1WT facilitated ubiquitination of endogenous proteins, whereas Myc-Kf-1DeltaR did not show ubiquitin ligase activity. In addition, we found that Kf-1 interacted with components of the ER-associated degradation (ERAD) pathway, including Derlin-1 and VCP. Taken together, these properties suggest that Kf-1 is an ER ubiquitin ligase involved in the ERAD pathway.
authors.affiliation: Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8553, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Misa
authors.initials: M
authors.lastname: Yamada
authors.forename: Kou
authors.initials: K
authors.lastname: Takahashi
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Yamada
mesh_terms: D000818:Animals; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C484500:Rnf103 protein, rat; C105129:RNF103 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex