Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance [Protein Synthesis and Degradation]
In this study, we found that two TQC enzymes, the ER-associated degradation ubiquitin ligase Hrd1 and zinc metalloprotease Ste24, promote degradation of characterized translocon-associated substrates of the other enzyme in Saccharomyces cerevisiae. Although both enzymes contribute to substrate turnover, our results suggest a prominent role for Hrd1 in TQC. Yeast lacking both Hrd1 and Ste24 exhibit a profound growth defect, consistent with overlapping function. Remarkably, two mutations that mildly perturb post-translational translocation and reduce the extent of aberrant translocon engagement by a model substrate diminish cellular dependence on TQC enzymes. Our data reveal previously unappreciated mechanistic complexity in TQC substrate detection and suggest that a robust translocon surveillance infrastructure maintains functional and efficient translocation machinery.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Avery M. Runnebohm, Kyle A. Richards, Courtney Broshar Irelan, Samantha M. Turk, Halie E. Vitali, Christopher J. Indovina, Eric M. Rubenstein Tags: Accelerated Communications Source Type: research