Specific programme: Fondation JEROME LEJEUNE
UPV/EHU Partner Status:  Beneficiary
UPV/EHU PI: Ugo Mayor
Project start: 15/07/2015
Project end:   14/07/2017
 

Brief description:  Angelman Syndrome (AS) was first described in 1965, and it is caused by a loss of maternal contribution of the UBE3A gene, located on chromosome 15q. AS has an estimated incidence of 1:20,000 and results from lack of the ubiquitin E3 ligase UBE3A in the brain. Which proteins are regulated by the ubiquitination activity of UBE3A is still unknown. Which other enzymes of the ubiquitin system cooperate with UBE3A to regulate its function is also unknown. The project aims to understand the mechanisms by which tightly regulated levels of UBE3A are critical for appropriate brain development, in particular to identify and characterize the enzymes that co-regulate with UBE3A the ubiquitination of its substrates. The project will focus on elucidating the UBE3A-regulated molecular mechanisms in order to understand how the later failure in brain function originates. The project will use cell culture and the Drosophila model system to identify and validate the ubiquitination pathway used by the UBE3A E3 ligase in the context of a whole organism. This will allow us to identify candidate therapeutical targets that might lead in the future to the treatment of Angelman Syndrome.