Autophagy is a fundamental cellular process to remove cellular garbage. After all, the cell needs to get rid of its waste to function properly. The molecular pathways regulating autophagy were prominently studied in budding yeast, and ultimately led to a new paradigm in understanding how cells reuse their content. In 2016, the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his discoveries of the mechanisms for autophagy. These findings paved the way to a better understanding of the fundamental importance of autophagy in many physiological processes, such as adaptation to hunger or response to infection. Mutations in autophagy genes can cause disease in humans, like neurodegenerative diseases, infectious diseases, and cancer.
Ubiquitination is an enzymatic process that involves the bonding of a protein called ubiquitin to a substrate protein. One could refer to a molecular “kiss of death”, because ubiquitin “tags” the substrate for degradation. Even though autophagy is crucial for human health, the mechanistic aspect in the mammalian system are not fully understood. Many data in the literature suggest that ubiquitination drives cellular cleaning process via autophagy, but the regulators for this process- namely ubiquitin enzymes - are largely unexplored.
In order to understand the mechanisms of "self-digestion" and its regulation, Petra Ebner, a VBC PhD student in the lab of Fumiyo Ikeda at IMBA, performed an RNAi screen to pinpoint ubiquitin enzymes, which regulate autophagy.
“We identified a ubiquitin enzyme called BRUCE to be important for the later stage of autophagy. Because BRUCE has an important function for cell death and associated with cancer, there might also be a balancing action to regulate cancer. In the long-term, I hope that our findings could contribute to a better understanding of the regulation of cell death via autophagy in cancer cells,“ says Fumiyo Ikeda.