Topic: ubiquitination

The KCNH2 gene-encoded KV11.1 voltage-gated potassium channel, also known as hERG, is abundantly expressed in the heart and brain, and plays an essential role in stabilizing cardiac and neuronal membrane potentials. Loss-of-function KCNH2 mutations, as well as pharmacological suppressions of human KV11.1 channel function, have been associated with arrhythmia and epilepsy. The majority of disease-related mutations involve aberrant KV11.1 protein folding, resulting in enhanced endoplasmic reticulum (ER)-associated degradation and decreased cell-surface protein level. Despite previous identificat

The Angelman Syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of the maternally expressed UBE3A gene, which encodes an E3 ubiquitin ligase. Although considerable efforts have been put to dissect UBE3A function in the brain, the pathogenic mechanisms remain largely unknown and effective treatments are not available yet. Being an E3 ubiquitin ligase, defective ubiquitination, which may occur in either nuclear or cytosolic compartments, is thought to be a primary mechanism underlying synaptic dysfunction in AS. Increasing evidence indicates a tight functional interplay betwe

Angelman Syndrome (AS) is a neurodevelopmental disorder with complex symptomatology caused by the loss of maternal allele expression of one single gene in the brain, the ubiquitin E3 ligase UBE3A. Even if the underlying genetic basis of AS has previously been extensively described, the molecular mechanisms regulated by UBE3A ubiquitination in the brain remain highly elusive. Here we provide the first proteomic report of UBE3A-mediated ubiquitination events in a mammalian brain. In order to identify Ube3a substrates, we have combined our previously described bioUb mouse with a new mouse strain