Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways.

ABSTRACT:

Background

The small molecule Eeyarestatin I (ESI) inhibits the endoplasmic reticulum (ER)-cytosol dislocation and subsequent degradation of ERAD (ER associated protein degradation) substrates. Toxins such as ricin and Shiga/Shiga-like toxins (SLTx) are endocytosed and trafficked to the ER. Their catalytic subunits are thought to utilise ERAD-like mechanisms to dislocate from the ER into the cytosol, where a proportion uncouples from the ERAD process, recovers a catalytic conformation and destroys their cellular targets. We therefore investigated ESI as a potential inhibitor of toxin dislocation.

Methodology and principal findings

Using cytotoxicity measurements, we found no role for ES(I) as an inhibitor of toxin dislocation from the ER, but instead found that for SLTx, ESI

SUBMITTER: Aletrari MO 

PROVIDER: S-EPMC3143184 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature