The complete characterization of the ubiquitination pathway of an UBE3A substrate is important due to the role of this E3 ligase in rare neurological disorders as Angelman syndrome.
Abnormal mTORC1 activation has been implicated in several developmental neurological disorders, including Angelman syndrome (AS), which is caused by maternal deficiency of the ubiquitin E3 ligase UBE3A.
Ube3a expression constitutes a direct mechanistic connection between symptoms of a human neurological disorder and the central circadian clock mechanism.
The ubiquitin ligase E6-AP (E6-associated protein) represents a prime example for the notion that deregulated modification of proteins with ubiquitin contributes to the development of human disease: loss of E6-AP function by mutation is responsible for the development of AS (Angelman syndrome), a neurological disorder, and unscheduled activation of E6-AP by complex formation with the E6 oncoprotein of HPVs (human papillomaviruses) contributes to cervical carcinogenesis.
The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder.
Disruption of the maternal copy of E6-AP is correlated with Angelman syndrome (AS), a genetic neurological disorder characterized by severe mental retardation, seizures, speech impairment, and other symptoms.