Philipp Alberts

TL;DR: This work used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography to report a method to target the myriad enzymes that govern ubiquitination of protein substrates.

TL;DR: The feasibility of identifying substrates and deciphering substrate specificity of mammalian E3 ligases is demonstrated and Nedd4‐1 knockdown or knockout in cells led to sustained signalling via some of its substrate Tyr kinases (e.g. FGFR), suggesting Nedd 4‐1 suppresses their signalling.

TL;DR: A feedback mechanism by which receptor tyrosine kinases promote catalytic activation of NEDD4 and that may represent a mechanism of receptor crosstalk is identified.

TL;DR: Human Nedd4 (Nedd4‐1), an E3 ubiquitin ligase comprised of a C2 domain, 4 WW domains, and a Hect domain, regulates endocytosis and signalling of FGFR1.

TL;DR: The studies indicate that LAPTM5 acts as a positive modulator of inflammatory signaling pathways and hence cytokine secretion in macrophages, and highlight a role for the endosomal/lysosomal system in regulating signaling via cytokine and pattern recognition receptors.