The E5 proteins

- E5 proteins are short transmembrane proteins encoded by many papillomaviruses.
- The E5 proteins display transforming activity in cultured cells and animals.
- The E5 proteins modulate the activity of cellular proteins.
- The BPV1 E5 activates the cellular PDGF β receptor in a ligand independent fashion.
- The EGF receptor appears to be an important target of the HPV16 E5 protein.

The E5 proteins are short transmembrane proteins encoded by many animal and human papillomaviruses. These proteins display transforming activity in cultured cells and animals, and they presumably also play a role in the productive virus life cycle. The E5 proteins are thought to act by modulating the activity of cellular proteins. Here, we describe the biological activities of the best-studied E5 proteins and discuss the evidence implicating specific protein targets and pathways in mediating these activities. The primary target of the 44-amino acid BPV1 E5 protein is the PDGF β receptor, whereas the EGF receptor appears to be an important target of the 83-amino acid HPV16 E5 protein. Both E5 proteins also bind to the vacuolar ATPase and affect MHC class I expression and cell-cell communication. Continued studies of the E5 proteins will elucidate important aspects of transmembrane protein-protein interactions, cellular signal transduction, cell biology, virus replication, and tumorigenesis.