USP14 inhibits ER-associated degradation via interaction with IRE1α

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

Research output: Contribution to journalArticle

21 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 languageEnglish
Pages (from-to)995-1000
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume379
Issue number4
DOIs
Publication statusPublished - 2009 Feb 20
Externally publishedYes

Fingerprint

Endoplasmic Reticulum-Associated Degradation
Endoplasmic Reticulum Stress
Unfolded Protein Response
Degradation
Endoplasmic Reticulum
Proteins
Ubiquitin-Specific Proteases
Protein Unfolding
Eukaryotic Cells
Corrosion inhibitors
Quality Control
Small Interfering RNA
Quality control
Control systems

Keywords

  • ER stress
  • ERAD
  • IRE1
  • USP14

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

USP14 inhibits ER-associated degradation via interaction with IRE1α. / Nagai, Atsushi; Kadowaki, Hisae; Maruyama, Takeshi; Takeda, Kohsuke; Nishitoh, Hideki; Ichijo, Hidenori.

In: Biochemical and Biophysical Research Communications, Vol. 379, No. 4, 20.02.2009, p. 995-1000.

Research output: Contribution to journalArticle

Nagai, Atsushi ; Kadowaki, Hisae ; Maruyama, Takeshi ; Takeda, Kohsuke ; Nishitoh, Hideki ; Ichijo, Hidenori. / USP14 inhibits ER-associated degradation via interaction with IRE1α. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 379, No. 4. pp. 995-1000.
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