Dr. Huibregte's lab studies the biochemistry of the ubiquitin proteolysis system, a major pathway for degradation of proteins in eukaryotic cells. In this pathway, the small protein, ubiquitin, is covalently linked to target proteins and serves as a signal for degradation by the proteasome. Dr. Huibregtse's interest in this pathway arose from study of human papillomaviruses (HPVs) and their association with uterine cervical carcinoma, the second leading cause of cancer-related deaths among women worldwide. Characterization of the E6 protein of these viruses showed that it promotes cellular immortalization by stimulating the ubiquitination and degradation of p53, an important tumor suppressor protein. This led to insights not only into how HPV-infected cells escape normal growth regulation, but also into basic mechanisms of how the enzymes of the ubiquitin system specifically recognize their correct targets. Current research projects continue to focus on HPVs and cancer, as well as on substrate specificity of the ubiquitin system in both mammalian and yeast cells.