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Speaker: Professor Henry Colecraft, Department of Physiology and Cellular Biophysics, Columbia University, New York, USA
Host: Mathias Gautel
Impaired protein stability or membrane trafficking underlies diverse ion channelopathies and represents an unexploited unifying principle to develop common treatments for otherwise dissimilar diseases. Ubiquitination limits ion channel surface density, but targeting this pathway for basic study or therapy is challenging because of its prevalent role in proteostasis. We developed engineered deubiquitinases (enDUBs) that enable ubiquitin chain removal selectively from target proteins to rescue functional expression of disparate mutant ion channels underlying Long QT syndrome (LQT1) and cystic fibrosis (CF). This talk will focus on targeted deubiquitination via enDUBs as a powerful and general protein stabilization method that not only corrects diverse diseases caused by impaired ion channel trafficking but also introduces a new tool for deconstructing the complex ubiquitin code in situ.