E3 ubiquitin ligases regulate protein turnover and signaling by mediating degradative or nondegradative types of ubiquitylation. In the 20 August 2026 issue of Science, Glassman et al. identified mechanisms by which viral proteins commandeer the ubiquitin-proteasome system to dysregulate innate immunity, unveiling pote...
Jun-Ji Zhu, Michaela U. Gack· Science Signaling· 0 citations
ABSTRACT All coronaviruses encode one or two multifunctional papain-like proteases (PLPs) with protease activity that cleaves the viral polyprotein, along with deubiquitinating (DUB) and deISGylase activities that remove ubiquitin and interferon-stimulated gene 15 (ISG15) from viral and host proteins. Studying the role...
Mudassir S. Ali, A. O'Brien, En-Ya Qing et al.· Journal of Virology· 0 citations
The coronavirus nucleocapsid (N) protein is indispensable for the viral lifecycle as part of the viral Replication-Transcription Complex together with Nsp3. Recent research demonstrated that phosphorylation of N by several host kinases intricately regulates its functions during infection. However, the mechanisms that c...
Jun-Ji Zhu, C. Chiang, Michaela U. Gack· bioRxiv· 0 citations
Genetically ablated the deISGylating activity of the SARS-CoV-2-encoded papain-like protease (PLpro) and found that loss of deISGylation boosted innate immune activation, attenuated viral replication, and promoted viral clearance in human cells and mice.