The server Protein-Protein Interaction of Chimeric Proteins

Milana Frenkel-Morgenstern's Cancer Genomics and BioComputing Lab at Bar-Ilan University, Israel
Alfonso Valencia Lab at CNIO: Centro Nacional de Investigaciones Oncológicas, Spain

Fusion proteins, comprising peptides deriving from the translation of two parental genes, are produced in cancer by means of chromosomal rearrangements or aberrations. The expressed fusion gene incorporates exons of both parental genes while maintaining intact protein domains and domain boundaries. Using a methodology that treats discreet protein domains as binding sites for specific domains of partner proteins, we have cataloged the partner proteins for 358 fusion proteins. We have developed ChiPPI, Chimeric protein-Protein-Interactions, which compares the protein domains in fusion proteins to the domains present in both parental proteins.

We predict where fusion proteins are likely to lose binding to partner proteins of the parent proteins. We have mapped the influence of fusion proteins on cellular protein-protein interaction (PPI) networks and on some essential pathways that lead to cancer development and progression. We find that the PPI networks of fusion proteins often lose tumor suppressor proteins, as well as being enriched in onco-proteins. Using PPI networks we show how fusion proteins contribute to the skewing of interaction networks as well as signaling pathways.

Highlights

Updates
  1. Domain-Domain co-occurrence measure for fusion protein interactions.
  2. Enrichment analysis for over-represented cancer-related pathways.
  3. For each PPI event, maintained and/or lost upon fusion of parental proteins are tracked.

  1. Linked with ProtFus tool for identifying protein-protein interactions in case of absence of known domains.
  2. Network structure information for fusion protein-protein interactions maps included.

Published