Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E08-03-0265 on July 23, 2008

Vol. 19, Issue 10, 4051-4061, October 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E08-03-0265v1
19/10/4051    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, S.-J.
Right arrow Articles by O'Farrell, P. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, S.-J.
Right arrow Articles by O'Farrell, P. H.

An RNA Interference Screen Identifies a Novel Regulator of Target of Rapamycin That Mediates Hypoxia Suppression of Translation in Drosophila S2 Cells

Soo-Jung Lee, Renny Feldman*, and Patrick H. O'Farrell

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-2517

Submitted March 12, 2008; Revised July 14, 2008; Accepted July 15, 2008
Monitoring Editor: Marvin Wickens

In addition to its central role in energy production, oxygen has pervasive regulatory actions. Hypoxia (oxygen limitation) triggers the shutdown of major cellular processes, including gene expression. We carried out a genome-wide RNA interference (RNAi) screen in Drosophila S2 cells for functions required to down-regulate translation during hypoxia. RNAi knockdown of specific genes allowed induction of a green fluorescent protein (GFP) reporter gene and continued protein synthesis during hypoxia. Among the identified genes, Tsc1 and Tsc2, which together form the tuberose sclerosis complex that negatively regulates target of rapamycin (TOR) kinase, gave an especially strong effect. This finding is consistent with the involvement of TOR in promoting translation. Another gene required for efficient inhibition of protein translation during hypoxia, the protein tyrosine phosphatase 61F (Ptp61F), down-regulates TOR activity under hypoxia. Lack of Ptp61F or Tsc2 improves cell survival under prolonged hypoxia in a TOR-dependent manner. Our results identify Ptp61F as a novel modulator of TOR activity and suggest that its function during hypoxia contributes to the down-regulation of protein synthesis.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-03-0265) on July 23, 2008.

* Present address: Gevo, Inc., 345 Inverness Drive South, Englewood, CO 80112.

Address correspondence to: Patrick H. O'Farrell (ofarrell{at}cgl.ucsf.edu)




This article has been cited by other articles:


Home page
 Mol. Biol. CellHome page
P. F. Dijkers and P. H. O'Farrell
Dissection of a Hypoxia-induced, Nitric Oxide-mediated Signaling Cascade
Mol. Biol. Cell, September 15, 2009; 20(18): 4083 - 4090.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.