HRD4/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins

被引：239

作者：

Bays, NW ^{[1
]}

Wilhovsky, SK ^{[1
]}

Goradia, A ^{[1
]}

Hodgkiss-Harlow, K ^{[1
]}

Hampton, RY ^{[1
]}

机构：

[1] Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA

来源：

MOLECULAR BIOLOGY OF THE CELL | 2001年 / 12卷 / 12期

关键词：

D O I：

10.1091/mbc.12.12.4114

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We isolated a temperature-sensitive mutant, hrd4-1, deficient in ER-associated degradation (ERAD). The HRD4 gene was identical to NPL4, a gene previously implicated in nuclear transport. Using a diverse set of substrates and direct ubiquitination assays, our analysis revealed that HRD4/NPL4 is required for a poorly characterized step in ERAD after ubiquitination of target proteins but before their recognition by the 26S proteasome. Our data indicate that this lack of proteasomal processing of ubiquitinated proteins constitutes the primary defect in hrd4/npl4 mutant cells and explains the diverse set of hrd4/npl4 phenotypes. We also found that each member of the Cdc48p-Ufd1p-Npl4p complex is individually required for ERAD.

引用

页码：4114 / 4128

页数：15

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