title: The new world of inorganic polyphosphates.
abstract: Post-translational modifications (PTMs) add regulatory features to proteins that help establish the complex functional networks that make up higher organisms. Advances in analytical detection methods have led to the identification of more than 200 types of PTMs. However, some modifications are unstable under the present detection methods, anticipating the existence of further modifications and a much more complex map of PTMs. An example is the recently discovered protein modification polyphosphorylation. Polyphosphorylation is mediated by inorganic polyphosphate (polyP) and represents the covalent attachment of this linear polymer of orthophosphate to lysine residues in target proteins. This modification has eluded MS analysis as both polyP itself and the phosphoramidate bonds created upon its reaction with lysine residues are highly unstable in acidic conditions. Polyphosphorylation detection was only possible through extensive biochemical characterization. Two targets have been identified: nuclear signal recognition 1 (Nsr1) and its interacting partner, topoisomerase 1 (Top1). Polyphosphorylation occurs within a conserved N-terminal polyacidic serine (S) and lysine (K) rich (PASK) cluster. It negatively regulates Nsr1-Top1 interaction and impairs Top1 enzymatic activity, namely relaxing supercoiled DNA. Modulation of cellular levels of polyP regulates Top1 activity by modifying its polyphosphorylation status. Here we discuss the significance of the recently identified new role of inorganic polyP.
authors: Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, U.K. dmcbado@ucl.ac.uk c.azevedo@ucl.ac.uk.
authors: Cristina
authors: C
authors: Azevedo
authors: Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, U.K. dmcbado@ucl.ac.uk c.azevedo@ucl.ac.uk.
authors: Adolfo
authors: A
authors: Saiardi
mesh_terms: D000818:Animals; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D011756:Diphosphates / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011122:Polyphosphates / Q000378:metabolism*
chemical_list: D011756:Diphosphates; D011122:Polyphosphates; D004264:DNA Topoisomerases, Type I; D008239:Lysine
keywords: inositol pyrophosphate; mobility shift; phosphate; pyrophosphorylation; signalling