Biomolecular engineering of intracellular switches in eukaryotes

Tools to selectively and reversibly control gene expression are useful to study and model cellular functions. When optimized, these cellular switches can turn a protein’s function “on” and “off” based on cues designated by the researcher. These cues include small molecules, drugs, hormones, and even...

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Bibliographic Details
Published in:Journal of drug delivery science and technology 2010-05, Vol.20 (3), p.163-169
Main Authors: Pastuszka, M.K., Mackay, J.A.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Cell switch
General pharmacology
Intein
Medical sciences
Molecular switch
Nuclear receptor
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Rapamycin
Riboswitch
RNAi
siRNA
Tet-Off
Tet-On
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Summary:Tools to selectively and reversibly control gene expression are useful to study and model cellular functions. When optimized, these cellular switches can turn a protein’s function “on” and “off” based on cues designated by the researcher. These cues include small molecules, drugs, hormones, and even temperature variations. Here we review three distinct areas in gene expression that are commonly targeted when designing cellular switches. Transcriptional switches target gene expression at the level of mRNA polymerization, with examples including the tetracycline gene induction system as well as nuclear receptors. Translational switches target the process of turning the mRNA signal into protein, with examples including riboswitches and RNA interference. Post-translational switches control how proteins interact with one another to attenuate or relay signals. Examples of post-translational modification include dimerization and intein splicing. In general, the delay times between switch and effect decreases from transcription to translation to post-translation; furthermore, the fastest switches may offer the most elegant opportunities to influence and study cell behavior. We discuss the pros and cons of these strategies, which directly influence their usefulness to study and implement drug targeting at the tissue and cellular level.
ISSN:1773-2247
DOI:10.1016/S1773-2247(10)50025-X