A retrospective evaluation of vitamin K for hemoptysis in adult cystic fibrosis patients.

Objectives: Hemoptysis is a complication in cystic fibrosis (CF) patients, and is associated with pulmonary exacerbations and hospitalizations. Pancreatic insufficiency is common in CF patients, and therefore these patients may benefit from the use of vitamin K therapy.

Methods: This was an observational study conducted in adult CF patients aiming to describe the utilization of vitamin K therapy in the setting of hemoptysis during an acute CF pulmonary exacerbation.

Structural basis for RING-Cys-Relay E3 ligase activity and its role in axon integrity.

MYCBP2 is a ubiquitin (Ub) E3 ligase (E3) that is essential for neurodevelopment and regulates axon maintenance. MYCBP2 transfers Ub to nonlysine substrates via a newly discovered RING-Cys-Relay (RCR) mechanism, where Ub is relayed from an upstream cysteine to a downstream substrate esterification site. The molecular bases for E2-E3 Ub transfer and Ub relay are unknown.

Tug of War in the Xenophagy World.

Xenophagy, the process of eliminating intracellular pathogens through the autophagy machinery, is an important defense mechanism against infectious disease, yet the underlying molecular mechanisms remain incompletely understood. Recent work (Xu et al., Cell, 2019) used the discovery of an inhibitor of xenophagy, SopF, to identify a SopF-sensitive mechanism that allows mammalian cells to detect invading bacteria.

Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity.

Ubiquitination is initiated by transfer of ubiquitin (Ub) from a ubiquitin-activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2), producing a covalently linked intermediate (E2-Ub) . Ubiquitin ligases (E3s) of the 'really interesting new gene' (RING) class recruit E2-Ub via their RING domain and then mediate direct transfer of ubiquitin to substrates . By contrast, 'homologous to E6-AP carboxy terminus' (HECT) E3 ligases undergo a catalytic cysteine-dependent transthiolation reaction with E2-Ub, forming a covalent E3-Ub intermediate.

Probes of ubiquitin E3 ligases enable systematic dissection of parkin activation.

E3 ligases represent an important class of enzymes, yet there are currently no chemical probes for profiling their activity. We develop a new class of activity-based probe by re-engineering a ubiquitin-charged E2 conjugating enzyme and demonstrate the utility of these probes by profiling the transthiolation activity of the RING-in-between-RING (RBR) E3 ligase parkin in vitro and in cellular extracts. Our study provides valuable insight into the roles, and cellular hierarchy, of distinct phosphorylation events in parkin activation.