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 journalArticlepeer-review

33 Citations (Scopus)


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
Issue number4
Publication statusPublished - 2009 Feb 20
Externally publishedYes


  • ER stress
  • ERAD
  • IRE1
  • USP14

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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