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Protein Polyphosphorylation of Lysine Residues by Inorganic Polyphosphate
Author(s) -
Azevedo Cristina,
Saiardi Adolfo
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.717.4
Subject(s) - polyphosphate , biogenesis , biochemistry , lysine , chemistry , ribosomal protein , dna , gene , serine , microbiology and biotechnology , biology , rna , amino acid , enzyme , ribosome , phosphate
Whole genome sequencing revealed that the complexity of higher organisms is not only linked to the number of genes but also to the evolution of a wide range of additional regulatory features such as post‐translational modification of proteins (PTMs). Almost all proteins can be modulated in this way, adding a level of complexity much greater than each gene product. PTMs can be very complex in nature and occur enzymatically and non‐enzymatically.
We identified and characterized a new PTM mediated by inorganic polyphosphate (polyP). This linear polymer of orthophosphate linked by ‘high‐energy’ phosphoanhydride bonds, analogous to those found in ATP, is ubiquitous in nature. We named this modification “polyphosphorylation” as it represents the covalent attachment of polyP to target proteins. We found that Nuclear signal recognition 1 (Nsr1) and its interacting partner, topoisomerase 1 (Top1) are polyphosphorylated at lysine residues within a conserved N‐terminal P oly A cidic serine ( S ) and lysine ( K ) rich (PASK) cluster. Polyphosphorylation negatively regulates Nsr1/Top1 interaction and impairs Top1 enzymatic activity of relaxing super coiled DNA. We demonstrate that modulation of cellular levels of polyP regulates Top1 activity by modifying its polyphosphorylation status. We propose that polyphosphorylation represents a new regulatory mechanism of acidic proteins known to be enriched in the nuclei of both yeast and mammalian cells. Polyphosphorylation of these proteins may add an additional layer of regulation to nuclear signaling, in particular to one of the most energy‐consuming and tightly regulated process in eukaryotic cells, ribosomal RNA biogenesis, where Nsr1 and Top1 play roles.