The Alarmone Diadenosine Tetraphosphate as a Cosubstrate for Protein AMPylation.

Diadenosine polyphosphates (Ap As) are non-canonical nucleotides whose cellular concentrations increase during stress and are therefore termed alarmones, signaling homeostatic imbalance. Their cellular role is poorly understood. In this work, we assessed Ap As for their usage as cosubstrates for protein AMPylation, a post-translational modification in which adenosine monophosphate (AMP) is transferred to proteins.

Chemical Proteomics of the Tumor Suppressor Fhit Covalently Bound to the Cofactor ApA Elucidates Its Inhibitory Action on Translation.

The tumor suppressor protein (Fhit) is known to be associated with genomic instability and apoptosis. The tumor-suppressive function of Fhit depends on the interaction with the alarmone diadenosine triphosphate (ApA), a noncanonical nucleotide whose concentration increases upon cellular stress. How the Fhit-ApA complex exerts its signaling function is unknown.