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Virology. 2013 Oct;445(1-2):99-114. doi: 10.1016/j.virol.2013.05.006. Epub 2013 May 31.

The E5 proteins.

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Department of Genetics, Yale School of Medicine, USA; Department of Therapeutic Radiology, Yale School of Medicine, USA; Department of Molecular Biophysics & Biochemistry, Yale University, USA; Yale Cancer Center, USA. Electronic address:


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.


Cervical cancer; EGF receptor; HPV; PDGF receptor; Papillomaviruses; Transmembrane proteins; Vacuolar ATPase

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