title: Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways.
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.
authors.affiliation: Department of Biological Statistics and Computational Biology Cornell University, Ithaca, NY 14853, USA.|Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.
authors.forename: Jishnu
authors.initials: J
authors.lastname: Das
authors.affiliation: Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Tommy V
authors.initials: TV
authors.lastname: Vo
authors.affiliation: Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.|Department of Medicine, Weill Cornell College of Medicine, New York, NY 10021, USA.
authors.forename: Xiaomu
authors.initials: X
authors.lastname: Wei
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, ON M5S-3E1, Canada.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Mellor
authors.affiliation: Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Tong
authors.affiliation: Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Degatano
authors.affiliation: Department of Biological Statistics and Computational Biology Cornell University, Ithaca, NY 14853, USA.|Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Cordero
authors.affiliation: Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.|Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Kruer-Zerhusen
authors.affiliation: Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.|CREST Research Project, JST, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Matsuyama
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Pleiss
authors.affiliation: Department of Medicine, Weill Cornell College of Medicine, New York, NY 10021, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Lipkin
authors.affiliation: Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.|CREST Research Project, JST, Kawaguchi, Saitama 332-0012, Japan.|Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Donnelly Centre, University of Toronto, Toronto, ON M5S-3E1, Canada.|Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, ON M5S-3E1, Canada.|Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02115.|Harvard Medical School, Boston, MA 02115.|Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, ON M5G-1X5, Canada.|Genetic Networks Program, Canadian Institute for Advanced Research, Toronto, ON M5G-1Z8, Canada.
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
authors.affiliation: Department of Biological Statistics and Computational Biology Cornell University, Ithaca, NY 14853, USA.|Weill Institute for Cell and Molecular Biology Cornell University, Ithaca, NY 14853, USA.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Yu
mesh_terms: D047468:Immunoprecipitation; D020543:Proteome; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
chemical_list: D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins