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# IFN-lambda map
## Map description
The Interferon-lambda (IFNL) map describes the action of the drug candidate IFNL on intra- and intercellular signal transduction and consists of two parts. The upper part of the map describes the binding of IFNL to its receptor, IFNLR, and the subsequent signaling cascade. IFNLR is preferentially expressed on epithelial cells [DOI 10.1016/j.immuni.2015.07.001]. JAK-STAT-signaling leads to the induction of Interferon Stimulated Genes (ISGs), which encode for antiviral proteins [DOI 10.1038/s41564-019-0421-x].
The bottom part describes the induction of transcription of IFNL in innate immune cells or infected lung epithelial cells. Intracellular RIG-1-like-receptor recognize viral RNA. This leads to activation of IRFs via the mitochondrial / peroxisomal MAVS pathway, which in turn leads to transcription of IFN-III genes [DOI 10.1038/ni.2924].
The interactions of viral proteins with the IFNL pathway are mapped where confirmed for SARS-CoV-2 [DOI 10.1101/2020.05.18.102467] or where amino acid sequence homology with SARS-CoV is big enough to assume the same mechanism for SARS-CoV-2 [DOI 10.1016/j.chom.2020.05.008].
## Cross-talk with other pathways (in the map, and in general)
IFNL may be the main IFN produced in lung cells during viral infection based on experiments with other respiratory viruses [DOI 10.1016/j.immuni.2015.07.001]. They may play a role in the so-called “cytokine storm” observed in some Covid-19 patients, as IFNL act more locally and lack the strong pro-inflammatory response associated with IFN type 1 [DOI 10.15252/emmm.202012465].
## Related pathways:
- PAMP signaling
- Interferon 1 pathway
- Virus replication cycle
- HCoVs IFN induction (WP4880)
## Creators (alphabetically)
Marta Conti
Marius Rameil
Vanessa Nakonecnij
## Contributors and reviewers
Marta Conti
Marius Rameil
Vanessa Nakonecnij
Jakob Vanhoefer
Jan Hasenauer
......@@ -6,8 +6,7 @@
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Authors:
<body>Authors:
Corinna Montrone, Gisela Fobo, Andreas Ruepp, Helmholtz Zentrum München / Institute of Experimental Genetics, Germany
Enrico Glaab, Luxembourg Centre for Systems Biomedicine (LCSB), Luxembourg
Description:
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# Orf10-Cul2 map
## Map description
The Orf10-Cul2 map describes the interaction of Orf10 with the ubiquitin-proteasome system. The ubiquitin-proteasome system regulates the intracellular sorting and degradation of proteins via ubiquitination, an enzymatic post-translational modification in which a ubiquitin protein is attached to a substrate protein. Polyubiquitination marks substrates for degradation by the 26S proteasome [DOI 10.1038/35056583]. Orf10 interacts with the ubiquitin-proteasome system by binding to different members of the Cul2-complex, a ubiquitin-ligase (E3) [DOI 10.1038/s41586-020-2286-9]. A particularly strong interaction was observed for the substrate adaptor Zyg11b [DOI 10.1038/s41586-020-2286-9], a RING finger protein. Under normal conditions, Zyg11b binds protein substrates with N-terminal glycine, but this binding might be altered by Orf10.
The map describes the ubiquitin-activating enzymes (E1s), the ubiquitin-conjugating enzymes (E2s), the Cul2-ubiquitin ligase (E3) and the 26S proteasome. The formation of the Cul2-complex and its interaction with Orf10 is included.
## Cross-talk with other pathways (in the map, and in general)
The ubiquitin-proteasome system is a key regulator of protein degradation and influences the levels of various proteins within the cell. This results in the modulation of cellular processes, including cell cycle progression and apoptosis [DOI: 10.1128/JVI.00485-10]. Furthermore, it has been shown that the ubiquitin-proteasome system plays an important role during various stages of the infection cycle of coronaviruses [DOI: 10.1128/JVI.00485-10]. RNA synthesis is modulated [DOI: 10.1128/JVI.00485-10] and antigen presentation on MHC class I molecules depends on proteasomal function [DOI 10.1681/ASN.2006010083].
## Creators
Jan Hasenauer & Leonard Schmiester
## Contributors and reviewers
Paul Stapor
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