Format

Send to

Choose Destination
Cell Rep. 2018 Mar 27;22(13):3427-3439. doi: 10.1016/j.celrep.2018.02.104.

A Screen for Candidate Targets of Lysine Polyphosphorylation Uncovers a Conserved Network Implicated in Ribosome Biogenesis.

Author information

1
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Ottawa Institute of Systems Biology, Ottawa, Ontario K1H 8M5, Canada.
2
Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada; Ottawa Institute of Systems Biology, Ottawa, Ontario K1H 8M5, Canada.
3
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada; Ottawa Institute of Systems Biology, Ottawa, Ontario K1H 8M5, Canada.
4
Department of Basic Sciences, New York University, College of Dentistry, 345 East 24(th) Street, New York, NY 10010, USA.
5
Conway Institute of Biomolecular & Biomedical Research & UCD School of Medicine & Medical Science, University College Dublin, Belfield, Dublin 4, Ireland.
6
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Ottawa Institute of Systems Biology, Ottawa, Ontario K1H 8M5, Canada. Electronic address: mdowne2@uottawa.ca.

Abstract

Polyphosphates (polyP) are chains of inorganic phosphates found in all cells. Previous work has implicated these chains in diverse functions, but the mechanism of action is unclear. A recent study reports that polyP can be non-enzymatically and covalently attached to lysine residues on yeast proteins Nsr1 and Top1. One question emerging from this work is whether so-called "polyphosphorylation" is unique to these proteins or instead functions as a global regulator akin to other lysine post-translational modifications. Here, we present the results of a screen for polyphosphorylated proteins in yeast. We uncovered 15 targets including a conserved network of proteins functioning in ribosome biogenesis. Multiple genes contribute to polyphosphorylation of targets by regulating polyP synthesis, and disruption of this synthesis results in translation defects as measured by polysome profiling. Finally, we identify 6 human proteins that can be modified by polyP, highlighting the therapeutic potential of manipulating polyphosphorylation in vivo.

KEYWORDS:

Ppn1; Ppn2; Vtc4; lysine polyphosphorylation; polyphosphate; ribosome biogenesis; yeast

PMID:
29590613
DOI:
10.1016/j.celrep.2018.02.104
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center