Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways. Academic Article Article uri icon

Overview

MeSH

  • Immunoprecipitation
  • Signal Transduction
  • Two-Hybrid System Techniques

MeSH Major

  • Proteome
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins

abstract

  • The fission yeast Schizosaccharomyces pombe has more metazoan-like features than the budding yeast Saccharomyces cerevisiae, yet it has similarly facile genetics. We present a large-scale verified binary protein-protein interactome network, "StressNet," based on high-throughput yeast two-hybrid screens of interacting proteins classified as part of stress response and signal transduction pathways in S. pombe. We performed systematic, cross-species interactome mapping using StressNet and a protein interactome network of orthologous proteins in S. cerevisiae. With cross-species comparative network studies, we detected a previously unidentified component (Snr1) of the S. pombe mitogen-activated protein kinase Sty1 pathway. Coimmunoprecipitation experiments showed that Snr1 interacted with Sty1 and that deletion of snr1 increased the sensitivity of S. pombe cells to stress. Comparison of StressNet with the interactome network of orthologous proteins in S. cerevisiae showed that most of the interactions among these stress response and signaling proteins are not conserved between species but are "rewired"; orthologous proteins have different binding partners in both species. In particular, transient interactions connecting proteins in different functional modules were more likely to be rewired than conserved. By directly testing interactions between proteins in one yeast species and their corresponding binding partners in the other yeast species with yeast two-hybrid assays, we found that about half of the interactions that are traditionally considered "conserved" form modified interaction interfaces that may potentially accommodate novel functions.

publication date

  • May 21, 2013

has subject area

  • Immunoprecipitation
  • Proteome
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Signal Transduction
  • Two-Hybrid System Techniques

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3777727

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2003350

PubMed ID

  • 23695164

Additional Document Info

start page

  • ra38

volume

  • 6

number

  • 276