From underlying chemistry to therapeutic potential: open questions in the new field of lysine polyphosphorylation
Polyphosphorylation is a newly described non-enzymatic post-translational modification wherein long chains of inorganic phosphates are attached to lysine residues. The first targets of polyphosphorylation identified were S. cerevisiae proteins Nsr1 and Top1. Building on this theme, we recently exploited functional genomics tools in yeast to identify 15 new targets, including a conserved network of nucleolar proteins implicated in ribosome biogenesis. We also described the polyphosphorylation of six human proteins, suggesting that this unique post-translational modification could be conserved throughout eukaryotes. The study of polyphosphorylation seems poised to uncover novel modes of protein regulation in pathways spanning diverse biological processes. In this review, we establish a framework for future work by outlining critical questions related to the biochemistry of polyphosphorylation, its therapeutic potential, and everything in between.
KeywordsPolyP Lysine polyphosphorylation Ppn1 Ppn2 Ppx1 Vtc4 EcPPK1
We thank the members of the Downey lab for critical review of the manuscript. Polyphosphate work in the Downey lab is funded by the Canadian Institutes of Health Research (PJT-148722).
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Conflict of interest
The authors declare no conflicts.
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