USP17 is required for peripheral trafficking of lysosomes.

Expression of the deubiquitinase USP17 is induced by multiple stimuli, including cytokines (IL-4/6), chemokines (IL-8, SDF1), and growth factors (EGF), and several studies indicate it is required for cell proliferation and migration. However, the mechanisms via which USP17 impacts upon these cellular functions are unclear. Here, we demonstrate that USP17 depletion prevents peripheral lysosome positioning, as well as trafficking of lysosomes to the cell periphery in response to EGF stimulation.

Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature.

Whilst there is an extensive body of preclinical nanomedicine research, translation to clinical settings has been slow. Here we present a novel approach to the targeted nanoparticle (NP) concept: utilizing both a novel targeting ligand, VNAR (Variable New Antigen Receptor), a shark-derived single chain binding domain, and an under-investigated target in delta-like ligand 4 (DLL4). We describe the development of an anti-DLL4 VNAR and the site-specific conjugation of this to poly(lactic-co-glycolic) acid PEGylated NPs using surface maleimide functional groups.

USP17 is required for trafficking and oncogenic signaling of mutant EGFR in NSCLC cells.

Background: The deubiquitinase USP17 is overexpressed in NSCLC and has been shown to be required for the growth and motility of EGFR wild-type (WT) NSCLC cells. USP17 is also required for clathrin-mediated endocytosis of EGFR. Here, we examine the impact of USP17 depletion on the growth, as well as EGFR endocytosis and signaling, of EGFR mutant (MT) NSCLC cells.

Clearance of intracellular Klebsiella pneumoniae infection using gentamicin-loaded nanoparticles.

Klebsiella pneumoniae is a foremost gram-negative pathogen that can induce life-threatening nosocomial pulmonary infections. Although it can be phagocytosed successfully by lung resident macrophages, this pathogen remains viable within vacuolar compartments, resulting in chronic infection and limiting therapeutic treatment with antibiotics. In this study, we aimed to generate and evaluate a cell-penetrant antibiotic poly(lactide-co-glycolide) (PLGA)-based formulation that could successfully treat intracellular K.

Deubiquitylating enzymes in receptor endocytosis and trafficking.

In recent times, our knowledge of the roles ubiquitin plays in multiple cellular processes has expanded exponentially, with one example being the role of ubiquitin in receptor endocytosis and trafficking. This has prompted a multitude of studies examining how the different machinery involved in the addition and removal of ubiquitin can influence this process. Multiple deubiquitylating enzymes (DUBs) have been implicated either in facilitating receptor endocytosis and lysosomal degradation or in rescuing receptor levels by preventing endocytosis and/or promoting recycling to the plasma membrane.