TRIM21 - from intracellular immunity to therapy
- 1Centre for Immune Regulation, Institute of Immunology, Faculty of Medicine, University of Oslo, Norway
- 2Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Norway
- 3Protein and Nucleic Acid Chemistry Division, Medical Research Council, Laboratory of Molecular Biology, United Kingdom
Tripartite motif containing-21 (TRIM21) is a cytosolic ubiquitin ligase and antibody receptor that provides a last line of defense against invading viruses. It does so by acting as a sensor that intercepts antibody-coated viruses that have evaded extracellular neutralization and breached the cell membrane. Upon engagement of the Fc of antibodies bound to viruses, TRIM21 triggers a coordinated effector and signaling response that prevents viral replication while at the same time inducing an anti-viral cellular state. This dual effector function is tightly regulated by auto-ubiquitination and phosphorylation. Therapeutically, TRIM21 has been shown to be detrimental in adenovirus based gene therapy, while it may be favorably utilized to prevent tau aggregation in neurodegenerative disorders. In addition, TRIM21 may synergize with the complement system to block viral replication as well as transgene expression. TRIM21 can also be utilized as a research tool to deplete specific proteins in cells and zebrafish embryos. Here, we review our current biological understanding of TRIM21 in light of its versatile functions.
Keywords: TRIM21, antibody, Gene Therapy, virus, Infection
Received: 23 May 2019;
Accepted: 13 Aug 2019.
Edited by:Gestur Vidarsson, Sanquin Research, Netherlands
Reviewed by:Elisa Vicenzi, San Raffaele Hospital (IRCCS), Italy
David E. Levy, Department of Pathology, School of Medicine, New York University, United States
Copyright: © 2019 Foss, Bottermann, Jonsson, Sandlie, James and Andersen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Jan T. Andersen, Centre for Immune Regulation, Institute of Immunology, Faculty of Medicine, University of Oslo, Oslo, Norway, email@example.com