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Sci. Signal., 21 May 2013
Vol. 6, Issue 276, p. ra38
[DOI: 10.1126/scisignal.2003350]

RESEARCH ARTICLES

Cross-Species Protein Interactome Mapping Reveals Species-Specific Wiring of Stress Response Pathways

Jishnu Das1,2*, Tommy V. Vo2,3*, Xiaomu Wei2,4, Joseph C. Mellor5, Virginia Tong2, Andrew G. Degatano2, Xiujuan Wang1,2, Lihua Wang2, Nicolas A. Cordero2, Nathan Kruer-Zerhusen2,3, Akihisa Matsuyama6,7, Jeffrey A. Pleiss3, Steven M. Lipkin4, Minoru Yoshida6,7,8, Frederick P. Roth5,9,10,11,12,13, and Haiyuan Yu1,2{dagger}

1 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA.
2 Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.
3 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
4 Department of Medicine, Weill Cornell College of Medicine, New York, NY 10021, USA.
5 Donnelly Centre, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
6 Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan.
7 CREST Research Project, JST, Kawaguchi, Saitama 332-0012, Japan.
8 Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
9 Departments of Molecular Genetics and Computer Science, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
10 Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
11 Harvard Medical School, Boston, MA 02115, USA.
12 Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.
13 Genetic Networks Program, Canadian Institute for Advanced Research, Toronto, Ontario M5G 1Z8, Canada.

* These authors contributed equally to this work.

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.

{dagger} Corresponding author. E-mail: haiyuan.yu{at}cornell.edu

Citation: J. Das, T. V. Vo, X. Wei, J. C. Mellor, V. Tong, A. G. Degatano, X. Wang, L. Wang, N. A. Cordero, N. Kruer-Zerhusen, A. Matsuyama, J. A. Pleiss, S. M. Lipkin, M. Yoshida, F. P. Roth, H. Yu, Cross-Species Protein Interactome Mapping Reveals Species-Specific Wiring of Stress Response Pathways. Sci. Signal. 6, ra38 (2013).

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