@article{179266,
  author = {Akhee Sabiha Jahan and Elise Biquand and Raquel Mu{\~n}oz-Moreno and Agathe Le Quang and Chris Ka-Pun Mok and Ho Him Wong and Qi Wen Teo and Sophie Valkenburg and Alex Chin and Leo Lit Man Poon and Artejan Te Velthuis and Adolfo Garc{\'\i}a-Sastre and Caroline Demeret and Sumana Sanyal},
  title = {OTUB1 Is a Key Regulator of RIG-I-Dependent Immune Signaling and Is Targeted for Proteasomal Degradation by Influenza A NS1},
  abstract = { Deubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of~K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of~OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses. },
  year = {2020},
  journal = {Cell Rep},
  volume = {30},
  pages = {1570-1584.e6},
  month = {02/2020},
  issn = {2211-1247},
  doi = {10.1016/j.celrep.2020.01.015},
  language = {eng},
}