The Adenoviral E4orf4 protein And The Cellular Metabolisim and Bioenergetics Of Cancer Cells : A Multifunctional Protein for a Multifactorial Disease

The adenovirus (Ad) E4orf4 protein is a multifunctional viral regulator. Within the context of the virus, E4orf4 contributes to temporal regulation of the progression of viral infection. However, when E4orf4 is expressed alone, it induces a unique, caspase-independent process of programmed cell death, which is preceded by a G2/M arrest in the cell cycle. Cell killing by E4orf4 is more efficient in several types of cancer cells in tissue culture than in normal healthy cells, and it can efficiently inhibit the tumorigenic process in vivo, in a Drosophila cancer model. E4orf4 resides at various cellular locations such as the nucleus and cytoplasm, and its cell death activity requires interactions with different host cell proteins simultaniously. As of recent findings, E4orf4 was also found to reside thrughout all of the mitochondria`s compartments, inhibiting its function and affecting the overall bioenergetics of the cells.

In light of the many transformations cancer cells undergo during their develoment, the multifunctionality of E4orf4 can be of great benefit . By using E4orf4 as a guide, affected celluar pathways can be targeted using combinations of in-market drugs , allowing to mimic the effect of E4orf4 solely on cancer cells, thus bypassing obstacles accompanied with the use of proteins as therputic agents and enabling us to take a better addvantage of resources we already possess.