Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress

DSpace/Manakin Repository

Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress

Citable link to this page

 

 
Title: Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress
Author: Lee, Samuel; Min Kim, Soo; Dotimas, James; Li, Letitia; Feener, Edward P; Baldus, Stephan; Myers, Ronald B; Chutkow, William A; Patwari, Parth; Yoshioka, Jun; Lee, Richard T

Note: Order does not necessarily reflect citation order of authors.

Citation: Lee, S., S. Min Kim, J. Dotimas, L. Li, E. P. Feener, S. Baldus, R. B. Myers, et al. 2014. “Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress.” EMBO Molecular Medicine 6 (6): 732-743. doi:10.15252/emmm.201302561. http://dx.doi.org/10.15252/emmm.201302561.
Full Text & Related Files:
Abstract: The endoplasmic reticulum (ER) is responsible for protein folding, modification, and trafficking. Accumulation of unfolded or misfolded proteins represents the condition of ER stress and triggers the unfolded protein response (UPR), a key mechanism linking supply of excess nutrients to insulin resistance and type 2 diabetes in obesity. The ER harbors proteins that participate in protein folding including protein disulfide isomerases (PDIs). Changes in PDI activity are associated with protein misfolding and ER stress. Here, we show that thioredoxin-interacting protein (Txnip), a member of the arrestin protein superfamily and one of the most strongly induced proteins in diabetic patients, regulates PDI activity and UPR signaling. We found that Txnip binds to PDIs and increases their enzymatic activity. Genetic deletion of Txnip in cells and mice led to increased protein ubiquitination and splicing of the UPR regulated transcription factor X-box-binding protein 1 (Xbp1s) at baseline as well as under ER stress. Our results reveal Txnip as a novel direct regulator of PDI activity and a feedback mechanism of UPR signaling to decrease ER stress.
Published Version: doi:10.15252/emmm.201302561
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203352/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454627
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters