Professor in Molecular Genetics & Microbiology
Graduate Advisor, Cell and Molecular Biology Graduate Program
Main Office: MBB 2.312
Phone: (512) 232-7700
Alternate Office: MBB 2.312
Alt. Phone: (512) 232-7701
The University of Texas at Austin
Institute for Cellular and Molecular Biology
2500 Speedway Stop A4800
Austin ,TX 78712-1191
Research SummaryThe Huibregtse lab studies the biochemistry of the ubiquitin proteolysis system, a major pathway for degradation of proteins in eukaryotic cells. Our interest in this pathway arose from study of human papillomaviruses (HPVs) and their association with uterine cervical cancer, the second leading cause of cancer-related deaths among women worldwide. Characterization of the HPV E6 protein showed that it promotes cellular immortalization by stimulating the ubiquitination and degradation of p53, an important tumor suppressor protein. This has led to insights not only into how HPV-infected cells escape normal growth regulation, but also to the identification of a class of ubiquitin ligases, known as HECT ubiquitin ligases. Our work in this area now focuses on understanding the biochemical mechanism and biological functions of HECT E3s in both mammalian and yeast cells. One of our goals is to use this information for developing small molecules that can modulate the activities of these enzymes in cells.
A second area of investigation concerns the function of ISG15, an interferon-induced ubiquitin-like protein (Ubl). Ubls are conjugated to cellular proteins through pathways that are parallel but distinct from those for ubiquitin, and each Ubl has its own distinct signaling functions. ISG15 is anti-viral activity against a range of virus types, and the goal of our work is to understand the biochemical basis of its anti-viral activity and the mechanism of its conjugation. We have recently shown that ISG15 also has anti-microbial activity through a mechanism completely distinct from its intracellular conjugation function. Remarkably, ISG15 functions as an activator of interferon-gamma expression, and it does so by being secreted from cells that have been infected by certain microbes, including mycobacteria.