Publications by authors named "Gus Warren"
Ubiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence or structural homology to eukaryotic ubiquitin regulators.
View Article and Find Full Text PDFArticle Synopsis
- - The rising obesity rates in the US have led to increased importance of medical treatments, with this study comparing costs of GLP-1 Receptor Agonists versus bariatric surgery for weight management in 2023.
- - The analysis showed that for drugs like Saxenda and Wegovy, the costs of ongoing GLP-1 use quickly exceed the one-time costs of bariatric procedures like Roux-en-Y gastric bypass and sleeve gastrectomy.
- - While the study emphasizes long-term cost considerations, it also acknowledges the potential for delayed effectiveness of GLP-1 medications and the risk of weight regain after stopping treatment, highlighting the need for a comprehensive view of financial and health trade-offs.
Article Synopsis
- Ubiquitination's ability to influence various biological processes in eukaryotes is tied to the different types of poly-ubiquitin chains, with K6-linked chains being of particular interest but difficult to study due to overlapping regulatory mechanisms.
- Research has identified LotA, a deubiquitinase from the pathogen Legionella pneumophila, that specifically targets and regulates K6-linked poly-ubiquitin chains, offering a clearer way to explore these signaling pathways.
- The study reveals how LotA not only activates deubiquitination but also possesses a unique adaptive ubiquitin-binding domain that prevents the mismanagement of critical proteins within the Legionella-containing vacuole during bacterial infection.
Evolution avoids a pathological stabilizing interaction in the immune protein S100A9.
Proc Natl Acad Sci U S A
October 2022
Stability constrains evolution. While much is known about constraints on destabilizing mutations, less is known about the constraints on stabilizing mutations. We recently identified a mutation in the innate immune protein S100A9 that provides insight into such constraints.
View Article and Find Full Text PDFMultifunctional proteins are evolutionary puzzles: how do proteins evolve to satisfy multiple functional constraints? S100A9 is one such multifunctional protein. It potently amplifies inflammation via Toll-like receptor four and is antimicrobial as part of a heterocomplex with S100A8. These two functions are seemingly regulated by proteolysis: S100A9 is readily degraded, while S100A8/S100A9 is resistant.
View Article and Find Full Text PDF