The human papillomavirus E7 oncoprotein

Abstract

The human papillomavirus (HPV) E7 oncoprotein shares functional similarities with such proteins as adenovirus E1A and SV40 large tumor antigen. As one of only two viral proteins always expressed in HPV-associated cancers, E7 plays a central role in both the viral life cycle and carcinogenic transformation. In the HPV viral life cycle, E7 disrupts the intimate association between cellular differentiation and proliferation in normal epithelium, allowing for viral replication in cells that would no longer be in the dividing population. This function is directly reflected in the transforming activities of E7, including tumor initiation and induction of genomic instability.

Figure 1. Schematic representation of the HPV E7 oncoprotein and affected cellular processes

The unstructured amino terminal 37 amino acid residues of HPV16 E7 have sequence similarity to a portion of CR1 (green) and the entire CR2 (red) of Ad E1A, with specific identical and chemically similar amino acid residues indicated by red and blue boxes, respectively. CR1 sequences are required for cellular transformation and pRB degradation but do not directly contribute to pRB binding. The core pRB binding site (LXCXE), also required for transformation, is located within CR2, adjacent to a casein kinase II consensus phosphorylation site (CKII). The carboxyl terminal E7 domain shown here is from HPV45 E7 as determined by X-ray crystallography (Ohlenschlager et al., 2006). This portion of the E7 sequence has a compact β1β2αIβ3α2 topology that represents a unique zinc-binding fold. The cysteine residues involved in zinc binding are indicated in yellow. They are arranged as two Cys-X-X-Cys motifs separated by 29 amino acid residues. Cellular processes affected by E7 and discussed in this chapter are indicated in the grey boxes. See text for details and references.