Many industrial and research biotechnology applications depend on predictable, controllable expression of exogenous proteins. On page 1298 , Stack et al. describe a method that allows regulation of the half-life of proteins of interest. The ubiquitin–proteasome pathway is responsible for the degradation of the great majority of cellular proteins. The authors manipulated this pathway by expressing proteins of interest as fusions with a mutant form of ubiquitin that is recognized as a degradation signal and targets proteins for proteasomal degradation. They show that increasing the number of ubiquitin units leads to a graded decrease in half-life and steady-state levels when fused to reporter proteins as well as cellular proteins, allowing fine-tuning of protein stability. Such fine-tuning could have diverse applications, such as modulating the accumulation of metabolic intermediates by altering key regulatory molecules in metabolic and signaling pathways. They also demonstrated that cells expressing a destabilized β-lactamase reporter could potentially function as a high-throughput model system for monitoring proteasomal degradation in living cells.