Fig. 2.

Protein interaction map of HAdV oncoproteins E1A, E1B and E4 and their connection to the hallmarks of cancer. Based on their relevance to the hallmarks of cancer, selected protein-protein interactions for E1A, E1B and E4 (including their isoforms) were visualized using Cytoscape [324]. Proteins shaded with light purple indicated a cellular target is shared by more than one of the HAdV proteins described in this review. Cancer-relevant cellular targets of each viral protein were identified from the literature and imported from the STRING database into Cytoscape. Interactions between cellular proteins were filtered to include only those with experimental evidence and high STRING confidence scores (>0.7). Targets of each viral protein have been colour coded according to their association with each respective hallmark of cancer. Importantly, each cellular target has a potential relevance to various hallmarks of cancer, even though their role in HAdV-mediated transformation may be unknown. Although an integrated analysis of E1A, E1B and E4 has yet to been performed, visualizing their interactions in this way demonstrates substantial overlap within the underlying interaction map. Notably, several cellular proteins, highlighted in purple, are targeted by multiple different viral proteins, suggesting potential synergy or antagonism on their function. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)