Towards a proteome-scale map of the human protein–protein interaction network

Abstract

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer

“…1A vs C). Annexin A2 (ANXA2), elongation factor 1 (EF1A), and glyceraldehyde-3-phosphate dehydrogenase (G3P) were shown previously to interact with PCNA [28][29][30][31][32], and the rest is reported here for the first time. The levels of three gene products involved in protein synthesis (RSSA, MDHM, and EF1A) were substantially higher in cancer than HMEC cells ( Fig.…”

“…The binding of PCNA to the annexin A2 ''membrane protein" was very surprising, since the localization of PCNA at the plasma membrane has never been reported. Nevertheless, it should be noted that the association of annexin A2 and PCNA was also found by another group [29]. Carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide, is associated with diverse pathological conditions; thus, it has been a target for drug developments for several human diseases, including glaucoma and cancer [38,39].…”

Functional atlas of the integrin adhesome

“…23,24 . This high ratio may be attributed to the fact that the components in the adhesome form a dense complex.…”

“…A partial view of the network, constructed with Cytoscape 18 , is illustrated in Fig. 1 -it 22 , or compared with high-throughput experiments 23,24 . This high ratio may be attributed to the fact that the components in the adhesome form a dense complex.…”

The transcription factor ERG recruits CCR4–NOT to control mRNA decay and mitotic progression

“…A stringent Y2H screening was performed in the reciprocal orientation, strictly as described in ref. 58. Colonies positive for the GAL1::HIS3 and GAL1::ADE2 selective markers but negative for autoactivation were selected for PCR amplification and identification of interacting proteins by sequencing of the respective AD-and DB-ORFs.…”