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Details on Person Upon viral infection, type I interferons (IFNs) (such as IFN...
| Class:Id | Summation:9710962 |
|---|---|
| _displayName | Upon viral infection, type I interferons (IFNs) (such as IFN... |
| _timestamp | 2021-11-01 18:22:09 |
| created | [InstanceEdit:9710961] Shamovsky, Veronica, 2021-01-06 |
| literatureReference | [LiteratureReference:9705298] Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane [LiteratureReference:9710924] Molecular basis for the recognition of phosphorylated STAT1 by importin alpha5 [LiteratureReference:9710935] Regulated nuclear import of the STAT1 transcription factor by direct binding of importin-alpha [LiteratureReference:9710929] Arginine/lysine-rich nuclear localization signals mediate interactions between dimeric STATs and importin alpha 5 [LiteratureReference:9710937] Nuclear import by karyopherin-βs: recognition and inhibition [LiteratureReference:9710936] Structure of importin-beta bound to the IBB domain of importin-alpha [LiteratureReference:8985394] The JAK-STAT pathway at twenty [LiteratureReference:9708890] SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling [LiteratureReference:9757400] Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins [LiteratureReference:9757398] Crosstalk between nucleocytoplasmic trafficking and the innate immune response to viral infection [LiteratureReference:9757498] Individual binding pockets of importin-beta for FG-nucleoporins have different binding properties and different sensitivities to RanGTP |
| modified | [InstanceEdit:9713617] Shamovsky, Veronica, 2021-01-27 [InstanceEdit:9713627] Shamovsky, Veronica, 2021-01-27 [InstanceEdit:9736370] Shamovsky, Veronica, 2021-07-07 [InstanceEdit:9757390] Shamovsky, Veronica, 2021-10-29 [InstanceEdit:9757519] Shamovsky, Veronica, 2021-11-01 |
| text | Upon viral infection, type I interferons (IFNs) (such as IFN-a/b) stimulate the transcription of antiviral interferon-stimulated genes (ISGs) by triggering phosphorylation, dimerization of signal transducer and activator of transcription 1 (STAT1) and STAT2, formation of interferon-stimulated gene factor 3 (ISGF3) complex with interferon regulatory factor 9 (IRF9), and nuclear translocation of of ISGF3 complex (Stark GR et al. 2012). STAT1 contains a nonclassical nuclear localization signal (NLS) sequence which is exposed only upon phosphorylation‑induced homo‑ or heterodimerization of STAT1 (Nardozzi J et al. 2010; Fagerlund R et al. 2002; McBride KM et al. 2002). In the cytoplasm, the nonclassical NLS of STAT1 dimers is initially recognized by an adaptor molecule, importin subunit α‑5 (also known as karyopherin subunit α‑1 or KPNA1) (McBride KM et al. 2002; Nardozzi J et al. 2010). KPNA1 then recruits importin β‑1 (karyopherin subunit β‑1 or KPNB1) via the N‑terminal importin β binding (IBB) domain of KPNA1 to form the NLS‑cargo:KPNA1:KPNB1 ternary complex (Cingolani G et al. 1999). The formed NLS‑cargo:KPNA1:KPNB1 complex is targeted to the nuclear pore complex (NPC) and then passes through nuclear pores via the interaction of KPNB1 with phenylalanine-glycine repeats (FG- repeats) (Moroianu J et al. 1995; McBride KM et al. 2002; Otsuka S et al. 2008; Chook YM & Süel KE. 2011). Many viruses encode proteins that subvert nuclear transport of activated STAT1 to antagonize the IFN signaling pathway (Shen Q et al. 2021). For example, severe acute respiratory syndrome coronavirus type 1 (SARS‑CoV-1) encodes an accessory protein orf6 which is thought to block the nuclear import of STAT1 by binding and tethering KPNA2 and KPNB1 to the endoplasmic reticulum (ER)/Golgi intermediate compartment (ERGIC) thus limiting free KPNB1 in the cytoplasm and reducing the p-STAT1:KPNA1:KPNB1 complex formation (Frieman M et al. 2007). Similar findings were reported for SARS-CoV-2 orf6 which interacts with KPNA2 (Xia H et al. 2020) and blocks the nuclear import of STAT1 (Lei X et al. 2020). In addition, SARS-CoV-2 orf6 also blocks STAT1 nuclear translocation by interacting with the NUP98:RAE1 complex. This disrupts the interaction between NUP98 and the p-STAT1:KPNA1:KPNB1 complex, thus preventing the docking of this complex at the nuclear pore (Miorin L et al. 2020). |
| (summation) | [Reaction:9710963] p-STAT1dimer:KPNA1 binds KPNB1 [Homo sapiens] |
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No pathways have been reviewed or authored by Upon viral infection, type I interferons (IFNs) (such as IFN... (9710962)
