Seminar

The ubiquitin ligase E6-AP and its role in human disease

Dr. Martin Scheffner

The E3 ubiquitin ligase E6-AP is a prime example for the notion that deregulation of modification of proteins by ubiquitin plays an important role in the development of human disease. E6-AP was originally identified as a protein that is utilized by the E6 oncoprotein of cancer-associated human papillomaviruses (HPVs) to target the tumor suppressor p53 for ubiquitin-dependent degradation. Thus, it is commonly assumed that unscheduled activation of E6-AP contributes to HPV-induced cervical carcinogenesis. Furthermore, E6-AP is encoded by the ube3a gene, which has been etiologically linked to the development of the Angelman syndrome (AS), a genetic neurological disorder. In fact, there is considerable evidence to suggest that loss of the E3 activity of E6-AP is sufficient to cause AS.

Despite its role in the development of cervical cancer and AS, the physiological functions as well as disease-relevant substrates of E6-AP are largely unknown. To understand the consequences of deregulation of E6-AP activity, we are using various approaches including RNA interference and quantitative mass spectrometry. The datasets generated will eventually contribute to identify cellular pathways that involve E6-AP and may be disturbed in cervical cancer and/or AS patients.