The E5 Transforming Gene of Bovine Papillomavirus Encodes a Small, Hydrophobic Polypeptide

Abstract

Bovine papillomavirus (BPV-1) contains two independent transforming genes that have been mapped to the E5 and E6 open reading frames (ORF's). The E5 transforming protein was identified by means of an antiserum against a synthetic peptide corresponding to the 20 COOH-terminal amino acids of the E5 ORF. The E5 polypeptide is the smallest viral transforming protein yet characterized; it had an apparent size of 7 kilodaltons. The transforming polypeptide is encoded entirely within the second half of the E5 ORF and its predicted amino acid composition is very unusual; 68% of the amino acids are strongly hydrophobic and 34% are leucine. Cell fractionation studies localized this polypeptide predominantly to cellular membranes.

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

“…E5 is a membrane-associated protein and found within the cell as a homodimer [28]. E5 primarily plays a role in the productive phase of the viral life cycle.…”

The bovine papillomavirus type 1 E6 oncoprotein sensitizes cells to tumor necrosis factor alpha-induced apoptosis

“…Each of these proteins is su cient to induce anchorage-independent growth and focus formation of C127 cells (DiMaio et al, 1986;Dvoretzky et al, 1980;Gro and Lancaster, 1986;Lowy et al, 1980;Schiller et al, 1984Schiller et al, , 1986Schlegel et al, 1986). BPV-1 E6-transformed C127 cells form tumors in nude mice (Schiller et al, 1984).…”

Mechanisms of cell transformation by papillomavirus E5 proteins

“…It is localized largely to the membranes of the endoplasmic reticulum and Golgi apparatus of transformed cells and exists as a dimer of two identical subunits linked by disul®de bonds involving cysteine residues in the carboxyl-terminal third of the protein (Burkhardt et al, 1989;Horwitz et al, 1988;Schlegel et al, 1986). The BPV E5 protein does not have intrinsic enzymatic activity but rather induces transformation by modulating the activity of cellular membrane proteins that regulate cell growth.…”

“…The BPV E5 protein is a very hydrophobic 44-amino acid type II transmembrane protein that can induce morphologic and tumorigenic transformation of rodent and human ®broblasts (Schlegel et al, 1986;. It is localized largely to the membranes of the endoplasmic reticulum and Golgi apparatus of transformed cells and exists as a dimer of two identical subunits linked by disul®de bonds involving cysteine residues in the carboxyl-terminal third of the protein (Burkhardt et al, 1989;Horwitz et al, 1988;Schlegel et al, 1986).…”