Saccharomyces cerevisiae Mub1, a substrate adaptor of E3 ubiquitin ligase Ubr2, modulates sensitivity to cell wall stressors through multiple transcription factors.

Yeasts evolved a complex regulatory programme to build and maintain their cell wall, the primary structure through which they interact with their environment. However, how this programme ties to essential cellular processes mostly remains unclear. Here, we focus on Saccharomyces cerevisiae MYND-type zinc finger protein MUB1 (Mub1), an adaptor protein of E3 ubiquitin-protein ligase Ubr2 that was previously associated with regulating proteasome genes through the transcription factor Rpn4. We show that S. cerevisiae cells lacking Mub1 become hyper-tolerant to standard cell wall stressors, outperforming wild-type cells. This protective mub1Δ phenotype stems from the activity of several transcription factors, leading to the inhibition of cell wall remodelling, a typically protective process that becomes maladaptive during chronic cell wall stress in laboratory conditions. Based on these results, we suggest that Mub1 regulates not only Rpn4 but a much broader range of transcription factors, and thus serves as an in-so-far unrecognised regulatory hub directly linking cell wall robustness with the ubiquitin-proteasome system.