Protein pyrophosphorylation by inositol pyrophosphates — detection, function, and regulation

Protein pyrophosphorylation is an emerging, unusual posttranslational modification. This signaling mechanism can be driven by inositol pyrophosphate messengers, which can convert a prephosphorylated protein to the corresponding pyrophosphoprotein. Endogenous protein pyrophosphorylation influences various cellular processes and signaling pathways, including the regulation of rRNA synthesis and the modulation of vesicular trafficking. Herein, we will summarize the current detection and analysis methods that have established the occurrence of pyrophosphorylation. These methods have also been used to explore the effects of pyrophosphorylation on protein structure and function. Putative mechanisms for the regulation of this intriguing, understudied modification will be discussed. Finally, the future needs for this developing area of signal transduction research are highlighted.