[Frontiers in Bioscience 13, 121-134, January 1, 2008]

Structure and function of the papillomavirus E6 protein and its interacting proteins

Yuqi Liu1, James D. Baleja1

1Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, U.S.A.


2. Introduction
3. E6 structure and function
4. Peptide interactors
5. Small molecule inhibitors that target E6 protein
6. PDZ domain interactors
7. Miscellaneous interactors
8. Remarks and Perspectives
9. Acknowledgements
10. References


Infection by high risk papillomavirus causes various forms of anogenital cancer including squamous cell carcinoma of the cervix. A primary step in the carcinogenesis includes formation of a complex of viral E6 protein and a human E3 ubiquitin ligase. This complex is competent to cause degradation and inactivation of several target proteins including human tumor suppressors which contributes to hyperproliferation of infected cells. Great insight on the mechanism by which E6 binds target proteins has recently been provided by determination of structures of interacting peptides and a E6 domain. These data have also provided a basis for the discovery of small molecules that can inhibit E6. However, there is still a need to further solve the structures of additional interacting complexes to identify the structural relationship that exists between proteins that simultaneously bind E6, such as E6AP and p53 or E6AP and PDZ domain-containing proteins, and to provide a clear picture of the interface between E6 and its ubiquitin ligase.