In the ubiquitin-proteasome system, substrates fated for destruction first acquire covalent modification by ubiquitin, and are subsequently destroyed by the proteasome. Traditionally, 26S proteasomes have been seen as largely uniform in their composition and functional capacity. Accordingly, cells can control proteasome abundance via transcriptional pathways that mediate concerted regulation of...

Cells communicate with their environment, in part, through cell surface receptors. Engineering receptors that both sense arbitrary inputs and provide outputs orthogonal to endogenous signaling pathways has been a challenge. Now, Lim and colleagues report a system based on synthetic Notch receptors that allows independent control of both inputs and outputs in diverse cell types.