Warts, cancer and ubiquitylation: lessons from the papillomaviruses.

Certain human papillomaviruses (such as HPV-16 and HPV-18) are associated with specific anogenital cancers, most notably cervical cancer. These viruses encode two oncoproteins, E6 and E7, which are expressed in the HPV positive cancers. E7 functions in cellular transformation, at least in part, through inactivation of pRB, and the other pRB related "pocket proteins" p107 and p130. The major target of the E6 oncoprotein encoded by the genital tract, cancer-associated human papillomaviruses is the p53 tumor suppressor protein. E6 binding to p53 is mediated by a cellular protein, the E6-associated protein (E6AP). In the presence of E6, E6AP catalyses the ubiquitylation and proteolysis of p53. E6AP is an E3 ubiquitin protein ligase and is not normally involved in the regulation of p53 stability in the absence of E6. E6AP is the prototype for the HECT domain family of E3 ubiquitin protein ligases.