To be (in a transcriptional complex) or not to be (promoting UBR5 ubiquitylation): That is an answer to how degradation controls gene expression.

Tsai et al.1 in this issue and Mark et al.2 in Cell reveal how the E3 ligase UBR5 mediates broad regulation by selectively targeting agonist-bound nuclear hormone receptors, MYC, and other transcriptional regulators not incorporated into active gene expression complexes.