RRC ID 34852
著者 Huang C, Harada Y, Hosomi A, Masahara-Negishi Y, Seino J, Fujihira H, Funakoshi Y, Suzuki T, Dohmae N, Suzuki T.
タイトル Endo-β-N-acetylglucosaminidase forms N-GlcNAc protein aggregates during ER-associated degradation in Ngly1-defective cells.
ジャーナル Proc Natl Acad Sci U S A
Abstract The cytoplasmic peptide:N-glycanase (PNGase; Ngly1 in mice) is a deglycosylating enzyme involved in the endoplasmic reticulum (ER)-associated degradation (ERAD) process. The precise role of Ngly1 in the ERAD process, however, remains unclear in mammals. The findings reported herein, using mouse embryonic fibroblast (MEF) cells, that the ablation of Ngly1 causes dysregulation of the ERAD process. Interestingly, not only delayed degradation but also the deglycosylation of a misfolded glycoprotein was observed in Ngly1(-/-) MEF cells. The unconventional deglycosylation reaction was found to be catalyzed by the cytosolic endo-β-N-acetylglucosaminidase (ENGase), generating aggregation-prone N-GlcNAc proteins. The ERAD dysregulation in cells lacking Ngly1 was restored by the additional knockout of ENGase gene. Thus, our study underscores the functional importance of Ngly1 in the ERAD process and provides a potential mechanism underlying the phenotypic consequences of a newly emerging genetic disorder caused by mutation of the human NGLY1 gene.
巻・号 112(5)
ページ 1398-403
公開日 2015-2-3
DOI 10.1073/pnas.1414593112
PII 1414593112
PMID 25605922
PMC PMC4321286
MeSH Acetylglucosamine / metabolism* Animals Cells, Cultured Endoplasmic Reticulum / metabolism* Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase / metabolism* Mice Mutation Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / genetics Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / metabolism* Radioimmunoprecipitation Assay
IF 9.412
引用数 46
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
遺伝子材料 pEF/RTAdelta/myc/ER (RDB13411) pEF/RTAdelta/V5-myc/ER (RDB13412) pEF/RTAdeltaN10Q/V5-myc/ER (RDB13413) pEF/RTAdeltaN236Q/V5-myc/ER (RDB13414) pEF/RTAdeltaN10QN236Q/V5-myc/ER (RDB13415) pEF/RTAdeltaN10DN236Q/V5-myc/ER (RDB13416) pcDNA3.1/ENGase/FLAG-His (RDB13417).