The Role of UBE2A and UBE3A in Motor- and Cognitive Function

The overall objective of this thesis is to try and understand the role of the Ubiquitin Proteasome pathway in two neurodevelopmental disorders. The Ubiquitin proteasome pathway is known for tagging proteins destined for degradation. The ubiquitination of a protein is a three-step process initiated with the E1 ubiquitin-activating enzyme. In the second step the activated ubiquitin is transferred to the E2 conjugating enzyme. Finally the E2 enzyme ubiquitin complex than transfers the activated ubiquitin to an E3 ligase-substrate complex. This thesis focuses on the UBE2A and UBE3A protein; both these proteins are associated with neurodevelopmental disorders. UBE2A is an E2 conjugating enzyme mutation/deletion cause UBE2A deficiency syndrome. UBE3A is an E3 ubiquitin ligase and mutation/deletion cause Angelman syndrome.