USP14 inhibits ER-associated degradation via interaction with IRE1α

Atsushi Nagai; Hisae Kadowaki; Takeshi Maruyama; Kohsuke Takeda; Hideki Nishitoh; Hidenori Ichijo

doi:10.1016/j.bbrc.2008.12.182

USP14 inhibits ER-associated degradation via interaction with IRE1α

Atsushi Nagai, Hisae Kadowaki, Takeshi Maruyama, Kohsuke Takeda, Hideki Nishitoh^*, Hidenori Ichijo

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

33 Citations (Scopus)

Abstract

Accumulation of unfolded proteins within the endoplasmic reticulum (ER) lumen induces ER stress. Eukaryotic cells possess the ER quality control systems, the unfolded protein response (UPR), to adapt to ER stress. IRE1α is one of the ER stress receptors and mediates the UPR. Here, we identified ubiquitin specific protease (USP) 14 as a binding partner of IRE1α. USP14 interacted with the cytoplasmic region of IRE1α, and the endogenous interaction between USP14 and IRE1α was inhibited by ER stress. Overexpression of USP14 inhibited the ER-associated degradation (ERAD) pathway, and USP14 depletion by small interfering RNA effectively activated ERAD. These findings suggest that USP14 is a novel player in the UPR by serving as a physiological inhibitor of ERAD under the non-stressed condition.

Original language	English
Pages (from-to)	995-1000
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	379
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.12.182
Publication status	Published - 2009 Feb 20
Externally published	Yes

Keywords

ER stress
ERAD
IRE1
USP14

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.12.182

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title = "USP14 inhibits ER-associated degradation via interaction with IRE1α",

abstract = "Accumulation of unfolded proteins within the endoplasmic reticulum (ER) lumen induces ER stress. Eukaryotic cells possess the ER quality control systems, the unfolded protein response (UPR), to adapt to ER stress. IRE1α is one of the ER stress receptors and mediates the UPR. Here, we identified ubiquitin specific protease (USP) 14 as a binding partner of IRE1α. USP14 interacted with the cytoplasmic region of IRE1α, and the endogenous interaction between USP14 and IRE1α was inhibited by ER stress. Overexpression of USP14 inhibited the ER-associated degradation (ERAD) pathway, and USP14 depletion by small interfering RNA effectively activated ERAD. These findings suggest that USP14 is a novel player in the UPR by serving as a physiological inhibitor of ERAD under the non-stressed condition.",

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author = "Atsushi Nagai and Hisae Kadowaki and Takeshi Maruyama and Kohsuke Takeda and Hideki Nishitoh and Hidenori Ichijo",

note = "Funding Information: We thank K. Nagata and N. Hosokawa for providing NHK plasmid; F. Urano for providing HRD1 and SEL1 plasmids; and K. Nakayama for providing HA-Ub plasmid. We also thank all the member of Cell Signaling Laboratory for valuable discussion. This study was supported by Grant-in-Aid for Scientific Research (S) and Grant-in-Aid for Scientific Research on a Priority Area from the Ministry of Education, Culture, Sports, Science and Technology, Japan.",

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AU - Nagai, Atsushi

AU - Kadowaki, Hisae

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AU - Takeda, Kohsuke

AU - Nishitoh, Hideki

AU - Ichijo, Hidenori

N1 - Funding Information: We thank K. Nagata and N. Hosokawa for providing NHK plasmid; F. Urano for providing HRD1 and SEL1 plasmids; and K. Nakayama for providing HA-Ub plasmid. We also thank all the member of Cell Signaling Laboratory for valuable discussion. This study was supported by Grant-in-Aid for Scientific Research (S) and Grant-in-Aid for Scientific Research on a Priority Area from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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N2 - Accumulation of unfolded proteins within the endoplasmic reticulum (ER) lumen induces ER stress. Eukaryotic cells possess the ER quality control systems, the unfolded protein response (UPR), to adapt to ER stress. IRE1α is one of the ER stress receptors and mediates the UPR. Here, we identified ubiquitin specific protease (USP) 14 as a binding partner of IRE1α. USP14 interacted with the cytoplasmic region of IRE1α, and the endogenous interaction between USP14 and IRE1α was inhibited by ER stress. Overexpression of USP14 inhibited the ER-associated degradation (ERAD) pathway, and USP14 depletion by small interfering RNA effectively activated ERAD. These findings suggest that USP14 is a novel player in the UPR by serving as a physiological inhibitor of ERAD under the non-stressed condition.

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USP14 inhibits ER-associated degradation via interaction with IRE1α

Abstract

Keywords

ASJC Scopus subject areas

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