Tunable signal processing through modular control of transcription factor translocation

Transcription Factor as Computer Cellular signaling pathways can serve to process information so that cells respond appropriately to various environmental stimuli. Hao et al. (p. 460) show that a single yeast transcription factor that is activated in response to stress—Msn2—can act as a signal processor. In an experimental setup in which the amplitude and duration of signaling in the cells could be tightly controlled, sites of phosphorylation on Msn2 that determine its transport into or out of the nucleus allowed it to have different dynamic responses depending upon the amplitude of the signal detected. The transcription factor could either track with the incoming signal, filter (ignore) it, or integrate it. Understanding such properties may be useful in designing behavior of biological control systems. A yeast protein transforms stress signals into distinct dynamic responses according to the timing and strength of inputs. Signaling pathways can induce different dynamics of transcription factor (TF) activation. We explored how TFs process signaling inputs to generate diverse dynamic responses. The budding yeast general stress–responsive TF Msn2 acted as a tunable signal processor that could track, filter, or integrate signals in an input-dependent manner. This tunable signal processing appears to originate from dual regulation of both nuclear import and export by phosphorylation, as mutants with one form of regulation sustained only one signal-processing function. Versatile signal processing by Msn2 is crucial for generating distinct dynamic responses to different natural stresses. Our findings reveal how complex signal-processing functions are integrated into a single molecule and provide a guide for the design of TFs with "programmable" signal-processing functions.