TY - JOUR
T1 - Rapid and orthogonal logic gating with a gibberellin-induced dimerization system
AU - Miyamoto, Takafumi
AU - DeRose, Robert
AU - Suarez, Allison
AU - Ueno, Tasuku
AU - Chen, Melinda
AU - Sun, Tai Ping
AU - Wolfgang, Michael J.
AU - Mukherjee, Chandrani
AU - Meyers, David J.
AU - Inoue, Takanari
N1 - Funding Information:
This study was supported in part by the US National Institutes of Health (NIH; gM092930 and DK090868 to T.I. and NS072241 to M.J.w), the US National Science Foundation (IOS-0641548 and MCB-0923723 to T.S.) and the National Center for Research Resources of the NIH and NIH Roadmap for Medical Research (UL1 RR 025005 to C.M. and D.J.M). T.U. is a recipient of a fellowship from the Japanese Society for the Promotion of Science. M.C. is a recipient of the Provost’s Undergraduate Research Award.
PY - 2012/5
Y1 - 2012/5
N2 - Using a newly synthesized gibberellin analog containing an acetoxymethyl group (GA3-AM) and its binding proteins, we developed an efficient chemically inducible dimerization (CID) system that is completely orthogonal to existing rapamycin-mediated protein dimerization. Combining the two systems should allow applications that have been difficult or impossible with only one CID system. By using both chemical inputs (rapamycin and GA3-AM), we designed and synthesized Boolean logic gates in living mammalian cells. These gates produced output signals such as fluorescence and membrane ruffling on a timescale of seconds, substantially faster than earlier intracellular logic gates. The use of two orthogonal dimerization systems in the same cell also allows for finer modulation of protein perturbations than is possible with a single dimerizer.
AB - Using a newly synthesized gibberellin analog containing an acetoxymethyl group (GA3-AM) and its binding proteins, we developed an efficient chemically inducible dimerization (CID) system that is completely orthogonal to existing rapamycin-mediated protein dimerization. Combining the two systems should allow applications that have been difficult or impossible with only one CID system. By using both chemical inputs (rapamycin and GA3-AM), we designed and synthesized Boolean logic gates in living mammalian cells. These gates produced output signals such as fluorescence and membrane ruffling on a timescale of seconds, substantially faster than earlier intracellular logic gates. The use of two orthogonal dimerization systems in the same cell also allows for finer modulation of protein perturbations than is possible with a single dimerizer.
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U2 - 10.1038/nchembio.922
DO - 10.1038/nchembio.922
M3 - Article
C2 - 22446836
AN - SCOPUS:84862815933
SN - 1552-4450
VL - 8
SP - 465
EP - 470
JO - Nature chemical biology
JF - Nature chemical biology
IS - 5
ER -