Genome-wide YFP fluorescence complementation screen identifies new regulators for telomere signaling in human cells.
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.
Severance Hospital Integrative Research Institute for Cerebral and Cardiovascular Disease, Yonsei University Health System, Seoul, Korea.
Ok-Hee
OH
Lee
Hyeung
H
Kim
Quanyuan
Q
He
Hwa Jin
HJ
Baek
Dong
D
Yang
Liuh-Yow
LY
Chen
Jiancong
J
Liang
Heekyung Kate
HK
Chae
Amin
A
Safari
Dan
D
Liu
Zhou
Z
Songyang
D001426:Bacterial Proteins / Q000737:chemistry*; D005434:Flow Cytometry / Q000379:methods; D005816:Genetic Complementation Test; D016678:Genome; D006801:Humans; D008164:Luminescent Proteins / Q000737:chemistry*; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry; D020543:Proteome; D012190:Retroviridae / Q000235:genetics; D000089804:Shelterin Complex; D015398:Signal Transduction; D016615:Telomere / Q000648:ultrastructure*; D034501:Telomere-Binding Proteins / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry
C495876:ACD protein, human; D001426:Bacterial Proteins; D008164:Luminescent Proteins; D011506:Proteins; D020543:Proteome; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D025801:Ubiquitin; C054562:yellow fluorescent protein, Bacteria; D044767:Ubiquitin-Protein Ligases