Protein Synthesis and Degradation
Tor comes to the fore in autophagy
Healthy cells are expert recyclers, rapidly breaking down worn-out or surplus macromolecules and reusing their building blocks. Several pathways, such as the proteasomal degradation route for protein breakdown, specifically pick out damaged or expendable molecules.Unfolding or aggregation, that is the question
Cellular processes accompanying protein aggregation are diverse and entangled, making it difficult to investigate the underlying molecular processes in a time-resolved way. Gottlieb, Thompson, and colleagues address this shortcoming using a chemical biology approach to monitor ubiquitination within the first 10 min after the initiation of protein aggregation. Intriguingly, unfolding rather than aggregation seems to trigger the observed events. This work might provide a method to answer open questions regarding the regulation of the proteostasis network upon protein misfolding.Interplay between ubiquitylation and SUMOylation: Empowered by phase separation
Ubiquitin and the ∼20 human ubiquitin-like proteins regulate numerous aspects of cell biology via interlinked mechanisms that have not been fully elucidated. Sha et al. now explore the interplay between ubiquitylation and SUMOylation, finding that inhibition of ubiquitylation enhances SUMOylation of hundreds of newly synthesized proteins and that the resultant pools are stored in phase-separated protein condensates called PML nuclear bodies. These unexpected outcomes identify a new role for SUMOylation and raise new questions about cell behavior under normal and stress conditions.Gained in translation: The power of digging deep into disease models
Mutations affecting the SECISBP2 protein necessary for selenocysteine incorporation are linked to human disease, but with a wide range of clinical outcomes. To gain insight into this diversity, Zhao et al. dissect the phenotypic and molecular consequences of two specific mutations in the Secisbp2 gene that partially disrupt selenoprotein synthesis. They observe surprising tissue-dependent effects, emphasizing the complexities of translational science.
