Molecular Bases of Disease
- The inter- and intracellular propagation of aggregated proteins like tau is emerging as a central mechanism behind progression of various neurodegenerative diseases. The steps by which tau aggregates and propagates is currently unclear. Chen et al. now combine a cell-based model of tau aggregation with a CRISPR interference (CRISPRi) genetic screen to identify components of the endosomal sorting complex required for transport (ESCRT) machinery as mediators of intracellular propagation of tau aggregates.
- Natriuretic peptides (NPs) are hormones involved in maintaining heart health that undergo proteolytic cleavage to become activated. Previous work has shown that O-GalNAc glycans affect their processing and activation. Here, Goetze, Schjoldager, and colleagues now provide comprehensive characterization of O-glycosylation of NPs, revealing that all members of the NP family can be modified by O-GalNAc glycans. Intriguingly, the study discovers glycans in the receptor-binding region of the A-type natriuretic peptide (ANP), demonstrating that they affect both stability and activity of ANP.
- In the late 1940s and early '50s, a husband-and-wife team at the University of Wisconsin–Madison (UW) changed the course of cancer research. In a series of six papers published in The Journal of Biological Chemistry (JBC) (1–6), James and Elizabeth Miller showed that cancer-causing chemicals, known as carcinogens, had to be metabolized and undergo enzymatic transformation in order to cause cancer. The first evidence that metabolized carcinogens can modify tissue components, such as nucleic acids and proteins, came from this work.