Discovery of ester-linked ubiquitylation of PARP10 mono-ADP-ribosylation in cells: a dual post-translational modification on Glu/Asp side chains.

The prevailing view on post-translational modifications (PTMs) is that amino acid side chains in proteins are modified with a single PTM at any given time. However, a growing body of work has demonstrated crosstalk between different PTMs, some occurring on the same residue. Such interplay is seen with ADP-ribosylation and ubiquitylation, where specialized E3 ligases ubiquitylate targets for proteasomal degradation in an ADP-ribosylation-dependent manner.

Bacterial esterases reverse lipopolysaccharide ubiquitylation to block host immunity.

Aspects of how Burkholderia escape the host's intrinsic immune response to replicate in the cell cytosol remain enigmatic. Here, we show that Burkholderia has evolved two mechanisms to block the activity of Ring finger protein 213 (RNF213)-mediated non-canonical ubiquitylation of bacterial lipopolysaccharide (LPS), thereby preventing the initiation of antibacterial autophagy. First, Burkholderia's polysaccharide capsule blocks RNF213 association with bacteria and second, the Burkholderia deubiquitylase (DUB), TssM, directly reverses the activity of RNF213 through a previously unrecognized esterase activity.

Dedicated bacterial esterases reverse lipopolysaccharide ubiquitylation to block immune sensing.

Pathogenic bacteria have evolved diverse mechanisms to counteract cell-autonomous immunity, which otherwise guards both immune and non-immune cells from the onset of an infection. The versatile immunity protein Ring finger protein 213 (RNF213) mediates the non-canonical ester-linked ubiquitylation of lipopolysaccharide (LPS), marking bacteria that sporadically enter the cytosol for destruction by antibacterial autophagy. However, whether cytosol-adapted pathogens are ubiquitylated on their LPS and whether they escape RNF213-mediated immunity, remains unknown.

Implementation of a unique mass casualty and emergency preparedness longitudinal learning experience for postgraduate year 2 pharmacy residents.

Background And Purpose: The American Society of Health-System Pharmacists (ASHP) postgraduate year 2 (PGY2) critical care pharmacy residency program offers an elective competency area, E3: Mass Casualty. Similar elective competencies are also available for PGY2 emergency medicine and postgraduate year 1/2 pharmacotherapy programs. Because of the COVID-19 pandemic, pharmacist proficiency in the management of disasters is even more urgent.