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. 2011 Apr 26;7:485. doi: 10.1038/msb.2011.19

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Copyright © 2011, EMBO and Macmillan Publishers Limited

This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

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Experimental disruption of the gene circuit 3–5–6–7 abolishes the Rb–E2F bistable switch. (A) The Cdk2 inhibitor CVT-313 selectively blocks the mutual-inhibition feedback loop 5–6, but not the other three positive-feedback loops (9, 2–3–6, and 2–7). (B) Experimental protocol of serum-pulse stimulation and Cdk2 inhibition. At time 0, cells were serum-starved and at quiescence. See Materials and methods for details. (C) The influence of Cdk2 inhibition on E2F bistability. Each curve represents the histogram of the E2F–d2GFP distribution from approximately 5000 cells. The Cdk2 inhibitor dose and sample harvest time are as indicated. The dashed lines connecting the high and low E2F–d2GFP modes are for the guide of eyes.