Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Stochastic Receptor Expression Determines Cell Fate upon Interferon Treatment

Stochastic Receptor Expression Determines Cell Fate upon Interferon Treatment Stochastic Receptor Expression Determines Cell Fate upon Interferon Treatment ▿ Doron Levin , Daniel Harari and Gideon Schreiber * Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel ABSTRACT Type I interferons trigger diverse biological effects by binding a common receptor, composed of IFNAR1 and IFNAR2. Intriguingly, while the activation of an antiviral state is common to all cells, antiproliferative activity and apoptosis affect only part of the population, even when cells are stimulated with saturating interferon concentrations. Manipulating receptor expression by different small interfering RNA (siRNA) concentrations reduced the fraction of responsive cells independent of the interferon used, including a newly generated, extremely tight-binding variant. Reduced receptor numbers increased 50% effective concentrations (EC 50 s) for alpha interferon 2 (IFN-α2) but not for the tight-binding variant. A correlation between receptor numbers, STAT activation, and gene induction is observed. Our data suggest that for a given cell, the response is binary (+/−) and dependent on the stochastic expression levels of the receptors on an individual cell. A low number of receptors suffices for antiviral response and is thus a robust feature common to all cells. Conversely, a high number of receptors is required for antiproliferative activity, which allows for fine-tuning on a single-cell level. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

Stochastic Receptor Expression Determines Cell Fate upon Interferon Treatment

Stochastic Receptor Expression Determines Cell Fate upon Interferon Treatment

Molecular and Cellular Biology , Volume 31 (16): 3252 – Aug 15, 2011

Abstract

Stochastic Receptor Expression Determines Cell Fate upon Interferon Treatment ▿ Doron Levin , Daniel Harari and Gideon Schreiber * Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel ABSTRACT Type I interferons trigger diverse biological effects by binding a common receptor, composed of IFNAR1 and IFNAR2. Intriguingly, while the activation of an antiviral state is common to all cells, antiproliferative activity and apoptosis affect only part of the population, even when cells are stimulated with saturating interferon concentrations. Manipulating receptor expression by different small interfering RNA (siRNA) concentrations reduced the fraction of responsive cells independent of the interferon used, including a newly generated, extremely tight-binding variant. Reduced receptor numbers increased 50% effective concentrations (EC 50 s) for alpha interferon 2 (IFN-α2) but not for the tight-binding variant. A correlation between receptor numbers, STAT activation, and gene induction is observed. Our data suggest that for a given cell, the response is binary (+/−) and dependent on the stochastic expression levels of the receptors on an individual cell. A low number of receptors suffices for antiviral response and is thus a robust feature common to all cells. Conversely, a high number of receptors is required for antiproliferative activity, which allows for fine-tuning on a single-cell level.

Loading next page...
 
/lp/american-society-for-microbiology/stochastic-receptor-expression-determines-cell-fate-upon-interferon-vWdbbVgmVr

References (63)

Publisher
American Society For Microbiology
Copyright
Copyright © 2011 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.05251-11
pmid
21690295
Publisher site
See Article on Publisher Site

Abstract

Stochastic Receptor Expression Determines Cell Fate upon Interferon Treatment ▿ Doron Levin , Daniel Harari and Gideon Schreiber * Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel ABSTRACT Type I interferons trigger diverse biological effects by binding a common receptor, composed of IFNAR1 and IFNAR2. Intriguingly, while the activation of an antiviral state is common to all cells, antiproliferative activity and apoptosis affect only part of the population, even when cells are stimulated with saturating interferon concentrations. Manipulating receptor expression by different small interfering RNA (siRNA) concentrations reduced the fraction of responsive cells independent of the interferon used, including a newly generated, extremely tight-binding variant. Reduced receptor numbers increased 50% effective concentrations (EC 50 s) for alpha interferon 2 (IFN-α2) but not for the tight-binding variant. A correlation between receptor numbers, STAT activation, and gene induction is observed. Our data suggest that for a given cell, the response is binary (+/−) and dependent on the stochastic expression levels of the receptors on an individual cell. A low number of receptors suffices for antiviral response and is thus a robust feature common to all cells. Conversely, a high number of receptors is required for antiproliferative activity, which allows for fine-tuning on a single-cell level.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Aug 15, 2011

There are no references for this article.