Abstract

Scale-free protein interaction networks contain a small number of highly connected proteins, called hubs, and a large number of poorly connected proteins. Recently, several independent studies have elucidated that hub proteins are more likely to be essential to cell function than non-hub proteins. Deletion of a hub protein is more likely to be lethal than deletion of a non-hub protein. This concept defines the centrality-lethality rule; it indicates the importance of hub proteins in a complex protein network and the significance of the network architecture. Determination of the link number for a hub protein is obscure. Therefore, it is important to decide how many link numbers the hub proteins have. Here, we propose a new approach for determining the link number of hub proteins. Hub links were counted by locating the intersection point between the power-law distributions of essential and non-essential proteins. Application of this method to the Uetz database yielded an estimate of seven for the minimum number of hub protein links in yeast. Other public database (Ito, DIP, SGD, and BioGRID) predicted a different number of hub protein links. To assess the reliability of the centrality-lethality rule, we examined the essentiality of hub proteins in the protein interaction networks defined within each of the five public datasets: Uetz, Ito, DIP, SGD, and BioGRID. All five sites indicated that hub proteins were more likely to be essential than were non-hub proteins. This new method for determining the number of hub links is a useful tool for hub proteins.

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