Degradation elements coincide with cofactor binding sites in a short-lived transcription factor.

Elaborate control of gene expression by transcription factors is common to all kingdoms of life. In eukaryotes, transcription factor abundance and activity are often regulated by targeted proteolysis via the ubiquitin-proteasome system (UPS). The yeast MATα2 (α2) cell type regulator has long served as a model for UPS-dependent transcription factor degradation. Proteolysis of α2 is complex: it involves at least 2 ubiquitylation pathways and multiple regions of α2 affect its degradation. Such complexity also exists for the degradation of other UPS substrates. Here I review α2 degradation, most notably our recent identification of 2 novel degradation elements within α2 that overlap corepressor binding sites. I discuss possible implications of these findings and consider how principles of α2 proteolysis may be relevant to the degradation of other UPS substrates.