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Integrated Analysis of Posttranslational Modification Proteomes Reveals Interactions and Cell Cycle Regulatory Patterns in Toxoplasma gondii
Author(s) -
Silmon de Monerri Natalie C,
Yakubu Rama R,
Weiss Louis M,
Kim Kami
Publication year - 2016
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.30.1_supplement.864.13
Subject(s) - biology , proteome , toxoplasma gondii , palmitoylation , cell cycle , phosphorylation , microbiology and biotechnology , cell cycle protein , ubiquitin , computational biology , genetics , gene , biochemistry , cysteine , antibody , enzyme
Toxoplasma gondii is a highly successful protozoan parasite that senses and responds to stimuli by altering morphology at different life cycle stages. It is able to replicate inside nearly any type of nucleated cell, and therefore encounters different nutritional availabilities and environments that it must respond to. Given the role of protein posttranslational modifications (PTM) in signaling and sensing in eukaryotes, PTM are likely to play an important role in regulating how T. gondii responds to stimuli and makes life cycle stage transitions. Recent studies have mapped PTM proteomes in T. gondii , including phosphorylation, succinylation, palmitoylation and acetylation. Here, we aimed to gain a global understanding of the function of PTM in T. gondii, using published datasets and new unpublished datasets for ubiquitination, arginine methylation and O‐GlcNAcylation. By performing enrichment analysis using predefined gene sets, we identified pathways and compartments targeted by PTM in this organism. We show that many PTM in T. gondii occur on cell cycle‐regulated proteins whose expression peaks at specific time points during the cell cycle, representing checkpoint control points. Ubiquitination, phosphorylation and palmitoylation are also enriched in proteins upregulated at a critical time point in the transition between S and M phase. To understand how multiple PTM coregulate proteins in T. gondii , we used hypergeometric testing to score interactions between proteomes and interrogate the nature of their interactions. Surprisingly, we found a pool of proteins that are coregulated by both phosphorylation and arginine methylation, representing a novel interaction between these two modifications. A significant proportion of proteins are also coregulated by ubiquitination and palmitoylation. In current work, using protein interaction network analysis of PTM‐modified proteins, we aim to identify protein complex “hubs” that are regulated by multiple PTMs. Together, these analyses aim to detect pathways and hubs modified by PTM in parasites to sense and respond to stimuli. Support or Funding Information NIH grants AI93220 (L.M.W.), AI092801 (K.K.), and AI087625 (K.K.)