Interior of the cell showing the endoplasmic reticulum in purple. Image credit: Adapted from work by National Institute of General Medical Sciences, National Institutes of Health (CC BY-NC 2.0)
Just like factories make mistakes when producing products, cells make mistakes when producing proteins. In cells, a compartment called the endoplasmic reticulum is where about one third of all proteins are produced, and where new proteins undergo quality control. Damaged or misfolded proteins are removed by a process called endoplasmic reticulum-associated degradation (ERAD for short), because if damaged proteins accumulate, cells become stressed.
One type of ERAD is driven by a protein called Hrd1. Together with other components, Hrd1 labels damaged proteins with a ubiquitin tag that acts as a flag for degradation. Hrd1 has a paradoxical feature, however. To be active, Hrd1 tags itself with ubiquitin but this also makes it more prone to becoming degraded. How does Hrd1 remain active while avoiding its own degradation?
To address this question, Peterson et al. forced budding yeast cells to produce high levels of 23 different enzymes that remove ubiquitin tags. One of these enzymes, called Ubp1, was able remove the ubiquitin tag from Hrd1, though it had not been seen in the ERAD pathway before. Further experiments also showed that Ubp1 was able to regulate Hrd1 activity, making Ubp1 a regulator of Hrd1 dependent protein quality control.
Without protein quality control, damaged proteins can contribute to various diseases. ERAD is a common quality control system for proteins, present in many different species, ranging from yeast to animals. Therefore, understanding how ERAD works in budding yeast may also increase understanding of how human cells deal with damaged proteins.
