Interferon-induced ADP-ribosylation: technical developments driving ICAB discovery.

Abstract

Cells respond to a variety of internal and external stimuli by regulating the activities of different signalling cascades and cellular processes, often via chemical modifications of biological macromolecules that modulate their overall levels, biochemical activities or biophysical interactions. One such modification, termed ADP-ribosylation (ADPr), is emerging as an important player in the interferon (IFN) response, but the molecular targets and functions of ADP-ribosyltransferases within this core component of innate immunity still remains unclear. We and others have recently identified that stimulation of IFN signalling cascades promotes the formation of a novel cytosolic structure in human cells that is enriched in ADP-ribosyl modifications. Here, we propose to name these structures 'interferon-induced cytosolic ADPr bodies' (ICABs) and discuss their known components and potential functions. We also review methods to detect ICABs (and cellular ADPr in general) using a range of recently developed reagents. This lays the foundation for future studies aimed at elucidating the molecular functions of ICABs and ADPr in innate immune responses, which is a central unanswered question in the field.