Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination
Abstract
Deregulation of components of the ubiquitin-proteasome system contributes to the development of various diseases. A prominent example is the ubiquitin ligase E6AP/UBE3A, which is associated with three disorders: in complex with the E6 oncoprotein of human papillomaviruses, it contributes to cervical carcinogenesis; loss of E6AP expression results in the development of Angelman syndrome; and increased E6AP expression has been associated with autism spectrum disorders. This indicates that E6AP has to be tightly controlled; however, only little is known about how this is achieved. By analyzing the role of ubiquitin and the E6 oncoprotein in E6AP-mediated ubiquitination, we provide evidence that E6AP exists in an active state and a latent state and that its activity is controlled by allosteric effectors.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- August 2015
- DOI:
- 10.1073/pnas.1505923112
- Bibcode:
- 2015PNAS..112.9872M