The Library
Dislocation of ricin toxin A chains in human cells utilizes selective cellular factors
Tools
Tools
Tools
Redmann, V., Oresic, K., Tortorella, L. L., Cook, Jonathan P., Lord, Mike (J. Mike) and Tortorella, D. (2011) Dislocation of ricin toxin A chains in human cells utilizes selective cellular factors. Journal of Biological Chemistry, Vol.286 (No.24). pp. 21231-21238. doi:10.1074/jbc.M111.234708
Full text not available from this repository, contact author.
Official URL: http://dx.doi.org/10.1074/jbc.M111.234708
Abstract
Ricin is a potent A-B toxin that is transported from the cell surface to the cytosol, where it inactivates ribosomes, leading to cell death. Ricin enters cells via endocytosis, where only a minute number of ricin molecules reach the endoplasmic reticulum (ER) lumen. Subsequently, the ricin A chain traverses the ER bilayer by a process referred to as dislocation or retrograde translocation to gain access to the cytosol. To study the molecular processes of ricin A chain dislocation, we have established, for the first time, a human cell system in which enzymatically attenuated ricin toxin A chains (RTA(E177D) and RTA(Delta 177-181)) are expressed in the cell and directed to the ER. Using this human cell-based system, we found that ricin A chains underwent a rapid dislocation event that was quite distinct from the dislocation of a canonical ER soluble misfolded protein, null Hong Kong variant of alpha(1)-antitrypsin. Remarkably, ricin A chain dislocation occurred via a membrane-integrated intermediate and utilized the ER protein SEL1L for transport across the ER bilayer to inhibit protein synthesis. The data support a model in which ricin A chain dislocation occurs via a novel strategy of utilizing the hydrophobic nature of the ER membrane and selective ER components to gain access to the cytosol.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Endoplasmic reticulum, Saccharomyces cerevisiae, Ricin, Toxins, Golgi apparatus, Cytosol | ||||
| Journal or Publication Title: | Journal of Biological Chemistry | ||||
| Publisher: | American Society for Biochemistry and Molecular Biology | ||||
| ISSN: | 0021-9258 | ||||
| Official Date: | 17 June 2011 | ||||
| Dates: |
|
||||
| Volume: | Vol.286 | ||||
| Number: | No.24 | ||||
| Page Range: | pp. 21231-21238 | ||||
| DOI: | 10.1074/jbc.M111.234708 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | National Institutes of Health (U.S.) (NIH), United States. Defense Threat Reduction Agency (DTRA), Irma T. Hirschl Trust | ||||
| Grant number: | AI060905 (NIH), W81XWH-10-2-0048 (DTRA) |
Data sourced from Thomson Reuters' Web of Knowledge
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
