Journal
FEBS JOURNAL
Volume 279, Issue 18, Pages 3329-3337Publisher
WILEY
DOI: 10.1111/j.1742-4658.2012.08623.x
Keywords
hysteresis; positive feedback; robustness; signal transduction pathway; switching system
Categories
Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science & Technology (MEST) [2009-0086964, 2010-0017662]
- World Class University (WCU) through the NRF [R32-2008-000-10218-0]
- MEST
- University of Seoul
- National Research Foundation of Korea [R32-2008-000-10218-0] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Hysteresis can be found in many physical systems, and a hysteretic switch has been used for various mechanical and electrical systems. Such a hysteretic switch can be created by using a single positive feedback loop, as often used in engineering systems. It is, however, intriguing that various cellular signaling systems use coupled positive feedback loops to implement the hysteretic switch. A question then arises about the advantage of using coupled positive feedback loops instead of simple isolated positive feedback for an apparently equivalent hysteretic switch. Through mathematical simulations, we determined that cellular systems with coupled positive feedback loops show enhanced hysteretic switching, and can thereby make a more reliable decision under conditions of noisy signaling. As most intracellular processes are accompanied by intrinsic noise, important cellular decisions such as differentiation and apoptosis need to be highly robust to such noises. The coupled positive feedback loops might have been evolutionarily acquired to enable correct cell fate decisions to be made through enhanced hysteretic switching in noisy cellular environments.
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