Regulation of Snf1 kinase by a cross talk between ubiquitylation and phosphorylation (LB256)

Abstract

A search for genes reported to interact with UBP8 and UBP10, coding for two highly‐conserved ubiquitin proteases required for deubiquitylation of histone H2B, revealed the yeast homologue of AMPK, SNF1. Snf1 is required when cellular glucose is limited, as it activates stress‐responsive transcription factors. We used a mutant that lacks Ubp8 and Ubp10 to investigate whether Snf1 is regulated by ubiquitylation and degradation. SNF1 mRNA levels in the mutant were no different to the wild type, but Snf1 protein levels were dramatically decreased. The decreased the level of Snf1 protein in the mutant was mediated ubiquitin proteasome pathway. Interestingly, the remaining Snf1 in the mutant was hyper‐phosphorylate when the glucose is exhausted; furthermore, we observed no change in tolerance to stress and lifespan, suggesting the sustainment of Snf1 activity. We hypothesize that Snf1 activity is enhanced in the mutant to compensate for the defect. When Snf1 activity approaches the adaptive level, the cell can overcome the stress and survive. In conclusion, our results suggest that Snf1 is protected from degradation by both Ubp8 and Ubp10. Adaptive hyper‐phosphorylated Snf1 might trigger stress‐responsive transcription and prevent Snf1 from being degraded further, thereby protecting cells against stress. We demonstrate the regulation of Snf1 by a crosstalk between phosphorylation and ubiquitylation.Grant Funding Source: Supported by National Science Council, Taiwan and Academia Sinica