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Series GSE70563 Query DataSets for GSE70563
Status Public on Nov 04, 2015
Title IRE1alpha is an endogenous substrate of endoplasmic reticulum-associated degradation
Organism Mus musculus
Experiment type Expression profiling by array
Summary Endoplasmic reticulum-associated degradation (ERAD) represents a principle quality control (QC) mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unknown. Here we discover that IRE1alpha, the sensor of unfolded protein response (UPR), is a bona fide substrate of the Sel1L-Hrd1 ERAD complex. Mechanistically, ERAD-mediated IRE1alpha degradation occurs in a Bip-dependent manner under basal conditions and is attenuated in response to ER stress. Both intramembrane hydrophilic residues of IRE1alpha and lectin protein OS9 are required for IRE1alpha degradation. ERAD deficiency causes IRE1alpha protein stabilization, accumulation and mild activation both in vitro and in vivo, leading to cellular hypersensitivity to ER stress and inflammation. Furthermore, though enterocyte-specific Sel1L-knockout mice (Sel1LΔIEC) are viable and appear normal, they are more susceptible to experimental colitis in an IRE1alpha-dependent but CHOP-independent manner. Collectively, these results demonstrate that Sel1L-Hrd1 ERAD serves a distinct, essential function in restraint of IRE1alpha signaling in vivo by managing its protein turnover.
 
Overall design Colon epithelium of wild type and enterocyte-specific Sel1L knockout mice were subjected to gene expression analysis.
 
Contributor(s) Sun S, Shi G, Sha H, Ji Y, Han X, Shu X, Ma H, Takamasa I, Gao B, Bu P, Guber RD, Shen X, Lee AH, Iwawaki T, Paton AW, Paton JC, Fang D, Tsai B, Yates III JR, Wu H, Kersten S, Long Q, Duhamel GE, Simpson KW, Qi L
Citation(s) 26551274
Submission date Jul 06, 2015
Last update date Mar 04, 2019
Contact name Guido Hooiveld
E-mail(s) guido.hooiveld@wur.nl
Organization name Wageningen University
Department Div. Human Nutrition & Health
Lab Nutrition, Metabolism & Genomics Group
Street address HELIX, Stippeneng 4
City Wageningen
ZIP/Postal code NL-6708WE
Country Netherlands
 
Platforms (1)
GPL6246 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]
Samples (6)
GSM1810421 Colonic epithelium, wild type, replicate 1
GSM1810422 Colonic epithelium, wild type, replicate 2
GSM1810423 Colonic epithelium, wild type, replicate 3
Relations
BioProject PRJNA289019

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Supplementary file Size Download File type/resource
GSE70563_RAW.tar 24.4 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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