Jakub Luptak

Keywords protein degradation autophagy innate immunity ubiquitin proteasome system antiviral immunity ubiquitin ligase targeted protein degradation xenophagy antibody antimicrobial response Introduction The E3 ubiquitin ligase TRIM21 is an intracellular antibody receptor that binds to antibody-coated viruses in the cytosol and mediates their degradation.1 TRIM21 is activated by dimerization of its RING domains, which is driven by clustering of multiple TRIM21 molecules around a substrate.2,3...

Harriet V. Mears, George R. Young, Theo Sanderson, Ruth Harvey, Jamie Barrett-Rodger, Rebecca Penn, Vanessa Cowton, Wilhelm Furnon, Giuditta De Lorenzo, Margaret Crawford, Daniel M. Snell, Ashley S. Fowler, Anob M. Chakrabarti, Saira Hussain, Ciarán Gilbride, Edward Emmott, Katja Finsterbusch, Jakub Luptak, Thomas P. Peacock, Jérôme Nicod, Arvind H. Patel, Massimo Palmarini, Emma Wall, Bryan Williams, Sonia Gandhi, Charles Swanton, David L. V. Bauer.

Abstract TRIM proteins are the largest family of E3 ligases in mammals. They include the intracellular antibody receptor TRIM21, which is responsible for mediating targeted protein degradation during Trim-Away. Despite their importance, the ubiquitination mechanism of TRIM ligases has remained elusive. Here we show that while Trim-Away activation results in ubiquitination of both ligase and substrate, ligase ubiquitination is not required for substrate degradation.