Endoplasmic reticulum stress response in coronavirus infection (Homo sapiens)
From WikiPathways
Description
Activated PERK inactivates eIF2α by phosphorylation, leading to a decrease in overall protein synthesis. eIF2α can also be phosphorylated by several other kinases (HRI, GCN2, PKR). PKR activation is shown to be suppressed by coronavirus nsp15 and dsRNA-binding activity of MERS-CoV protein 4a. Activated IRE1 (ERN1) has multiple downstream effects. The IRE1 RNase domain is involved in unconventional splicing of XBP1, creating XBP1S which induces expression of protein folding genes. The RNase domain can also break down mRNAs (IRE1-dependent mRNA decay, RIDD), helping to establish ER homeostasis. Finally, the kinase activity of IRE1 also activates a signaling cascade that leads to the JNK pathway, triggering apoptosis. It is thought that the SARS-CoV E protein suppresses activation of the IRE1 pathway and SARS-CoV-induced apoptosis [10.1371/journal.ppat.1002315]. Activated ATF6 is translocated to Golgi and cleaved [DOI: 10.1016/s1097-2765(00)00133-7] to release ATF6-p50, a transcription factor that induces the expression of protein chaperone genes as well as CHOP and XBP1. There is evidence that SARS-CoV infection inhibits ATF6 cleavage [10.1016/j.virol.2009.02.021].
Quality Tags
Ontology Terms
Saving...Bibliography
View all... |
- Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJP, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JCJ, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, Garcia-Sastre A, Shokat KM, Shoichet BK, Krogan NJ; ''A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.''; Nature, 2020 PubMed Europe PMC Scholia
- Fung TS, Liu DX; ''Human Coronavirus: Host-Pathogen Interaction.''; Annu Rev Microbiol, 2019 PubMed Europe PMC Scholia
- Cui W, Li J, Ron D, Sha B; ''The structure of the PERK kinase domain suggests the mechanism for its activation.''; Acta Crystallogr D Biol Crystallogr, 2011 PubMed Europe PMC Scholia
- Ye J, Rawson RB, Komuro R, Chen X, Davé UP, Prywes R, Brown MS, Goldstein JL; ''ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs.''; Mol Cell, 2000 PubMed Europe PMC Scholia
- DeDiego ML, Nieto-Torres JL, Jiménez-Guardeño JM, Regla-Nava JA, Alvarez E, Oliveros JC, Zhao J, Fett C, Perlman S, Enjuanes L; ''Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress response and apoptosis.''; PLoS Pathog, 2011 PubMed Europe PMC Scholia
- Sung SC, Chao CY, Jeng KS, Yang JY, Lai MM; ''The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6.''; Virology, 2009 PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
| View all... |
Annotated Interactions
No annotated interactions
