SKP2 mediated BECN1 ubiquitination, its role in autophagy, and how its inhibition reduces MERS-Coronavirus replication
Autophagy is an important mechanism used by host cells to counter viral infections. In this process, double-membrane vesicles called autophagosomes deliver viral cargo to the lysosomes for degradation. Autophagy also coordinates the presentation of the virus-derived antigens to T lymphocytes following degradation, thereby playing an important role in acquired immunity. Studies have shown that viruses either use autophagic pathways for their replication or have evolved mechanisms that help evade autophagic degradation.
In this article, Gassen et.al have studied the role of beclin1 (BECN1), a multifunctional protein crucial for autophagy and membrane trafficking processes. An elevated level of BECN1 is associated with increased autophagy induced by an HSP90 cochaperone, FKBP51. BECN1 is regulated by ubiquitination and phosphorylation, and MERS-coronavirus infection results in lowered BECN1 levels. The authors have used biochemical and flow cytometry assays to propose that the S-phase kinase-associated protein 2 (SKP2) is the E3 ligase that poly-ubiquitinates BECN1. They also propose that small molecule inhibitors of SKP2 reduce the ubiquitination and degradation of BECN1, enhance FKBP51 induced autophagy, and greatly reduce the replication of MERS-coronavirus. The authors conclude that the SKP2-BECN1 pathway holds promise as a target for host-directed antiviral drugs and other autophagy-related conditions.
Read the article in Nature Communications
BD and the BD Logo are trademarks of Becton, Dickinson and Company or its affiliates. © 2020 BD. All rights reserved.