Information processing in the NF-?B pathway
PBN-AR
Instytucja
Instytut Podstawowych Problemów Techniki Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
EN
Czasopismo
Scientific Reports (40pkt w roku publikacji)
ISSN
2045-2322
EISSN
Wydawca
DOI
Rok publikacji
2017
Numer zeszytu
Strony od-do
15926-15926
Numer tomu
7
Identyfikator DOI
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Słowa kluczowe
EN
cellular signaling networks
innate immunity
stress signaling
Streszczenia
Język
EN
Treść
The NF-?B pathway is known to transmit merely 1?bit of information about stimulus level. We combined experimentation with mathematical modeling to elucidate how information about TNF concentration is turned into a binary decision. Using Kolmogorov-Smirnov distance, we quantified the cell’s ability to discern 8 TNF concentrations at each step of the NF-?B pathway, to find that input discernibility decreases as signal propagates along the pathway. Discernibility of low TNF concentrations is restricted by noise at the TNF receptor level, whereas discernibility of high TNF concentrations it is restricted by saturation/depletion of downstream signaling components. Consequently, signal discernibility is highest between 0.03 and 1 ng/ml TNF. Simultaneous exposure to TNF or LPS and a translation inhibitor, cycloheximide, leads to prolonged NF-?B activation and a marked increase of transcript levels of NF-?B inhibitors, I?B? and A20. The impact of cycloheximide becomes apparent after the first peak of nuclear NF-?B translocation, meaning that the NF-?B network not only relays 1?bit of information to coordinate the all-or-nothing expression of early genes, but also over a longer time course integrates information about other stimuli. The NF-?B system should be thus perceived as a feedback-controlled decision-making module rather than a simple information transmission channel.
Cechy publikacji
original-article
Inne
System-identifier
5616
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