Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells

Mol Cell Proteomics. 2011 Feb;10(2):M110.001628. doi: 10.1074/mcp.M110.001628. Epub 2010 Nov 2.


Detection of low-affinity or transient interactions can be a bottleneck in our understanding of signaling networks. To address this problem, we developed an arrayed screening strategy based on protein complementation to systematically investigate protein-protein interactions in live human cells, and performed a large-scale screen for regulators of telomeres. Maintenance of vertebrate telomeres requires the concerted action of members of the Telomere Interactome, built upon the six core telomeric proteins TRF1, TRF2, RAP1, TIN2, TPP1, and POT1. Of the ∼12,000 human proteins examined, we identified over 300 proteins that associated with the six core telomeric proteins. The majority of the identified proteins have not been previously linked to telomere biology, including regulators of post-translational modifications such as protein kinases and ubiquitin E3 ligases. Results from this study shed light on the molecular niche that is fundamental to telomere regulation in humans, and provide a valuable tool to investigate signaling pathways in mammalian cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Flow Cytometry / methods
  • Genetic Complementation Test
  • Genome
  • Humans
  • Luminescent Proteins / chemistry*
  • Protein Interaction Mapping
  • Proteins / chemistry
  • Proteome
  • Retroviridae / genetics
  • Shelterin Complex
  • Signal Transduction
  • Telomere / ultrastructure*
  • Telomere-Binding Proteins / chemistry
  • Ubiquitin / chemistry
  • Ubiquitin-Protein Ligases / chemistry


  • ACD protein, human
  • Bacterial Proteins
  • Luminescent Proteins
  • Proteins
  • Proteome
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Ubiquitin
  • yellow fluorescent protein, Bacteria
  • Ubiquitin-Protein Ligases