IndraLab

Statements


USP18 affects IFNAR2
3 1 | 42 88
USP18 binds IFNAR2.
3 1 | 38 88
3 1 | 38 73

sparser
"The ISG ubiquitin specific peptidase 18 (USP18) binds to IFNAR2, preventing it from recruiting signal transducer and activator of transcription 1 (STAT1)."

sparser
"In STAT2-deficient cells, the USP18-mediated inhibition of type I interferon signalling was reduced and the interaction between IFNAR2 and USP18 was weakened pointing to an essential role of STAT2 in USP18-mediated inhibition of the type I interferon signalling pathway [58]."

reach
"Consistent with this, deletion of the STAT2 binding site on IFNAR2 reduced the binding of USP18 to IFNAR2 [50]."

reach
"These results established that USP18 independently interacts with IFNAR2 and STAT2."

sparser
"While it was first suggested that USP18 binding to IFNAR2 does not compete with ternary complex formation between IFNAR1, IFNAR2 and IFNα2 [56]."

sparser
"Furthermore, Usp18 functions in the type I IFN pathway by down-regulating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway independently of its isopeptidase activity through an interaction between Usp18 and the IFNAR2 subunit of the type I IFN receptor complex, while neither IFNAR1 nor IFNGR1 (type II IFN) receptor subunits were able to interact with Usp18 ( xref )."

reach
"We assume that recruitment of USP18 to IFNAR2 via STAT2 promotes the otherwise weak interaction of USP18 with a membrane proximal site of IFNAR2."

sparser
"Moreover, STAT2 can serve as an adaptor to bridge the interaction between USP18 and IFNAR2, which inhibits ligand binding to the receptor, resulting in decreased receptor dimerization and signaling ( xref )."

reach
"Gruber and colleagues confirmed this in coimmunoprecipitation experiments in transiently transfected U6A cells overexpressing WT or STAT2-R148Q and USP18, showing a reduced interaction between USP18 and IFNAR2 in the presence of STAT2-R148Q (Fig. 3) [57]."

sparser
"Specifically, murine USP18 can bind to human IFNAR2 and block type I IFN signaling by competitively interfering with Jak1 binding to the receptor [ xref ]."
| 10

sparser
"Mapping the STAT2 and USP18 binding to IFNAR2 by cell micropatterning of further deletions and mutations ( xref ) confirmed aa 418-444 of IFNAR2 as a minimal interaction site for STAT2 and USP18."

sparser
"Based on our previous report xref and the results presented above, USP18 interacts with both IFNAR2 and STAT2."

sparser
"Binding of STAT2 and USP18 to IFNAR2 is synergistic, in line with the previous observation that the STAT2-IFNAR2 interaction was strengthened by USP18 xref ."

sparser
"USP18 also interacts with IFNAR2 and STAT2 to block type I interferon signalling in a protease-independent manner."

sparser
"These results established that USP18 independently interacts with IFNAR2 and STAT2."

sparser
"USP18 binds STAT2 and IFNAR2, displacing JAK1 from the cytoplasmic domain of IFNAR2 and inducing a conformational change in the IFN-IFNAR1-IFNAR2 complex, leading to impaired signal transduction (left)."

sparser
"The reported interactions between USP18 and IFNAR2 as well as STAT2 remain to be characterised biochemically and structurally."

sparser
"More detailed analysis of the interaction dynamics of the STAT2IFNAR2 interaction in the presence of USP18 by FRAP ( xref ) revealed a dissociation rate constant of 0.015 ± 0.005 s −1 ."

sparser
"We next examined IFNAR2-independent interaction of STAT2 and USP18 in IFNAR2-deficient U5A cells by using cell micropatterning."

sparser
"Taken together, our data suggest that USP18 simultaneously interacts with IFNAR2 via STAT2 in the membrane distal region and directly in the membrane-proximal region ( xref )."
| 2

sparser
"Even though type III IFN signaling requires JAK1, it is not affected by USP18 as USP18 specifically targets and binds IFNAR2 and not IFNLR ( xref )."

sparser
"Even though type III IFN signaling requires JAK1, it is not affected by USP18 as USP18 specifically targets and binds IFNAR2 and not IFNLR (81)."
| 1

sparser
"USP18 can interact with IFNAR2 and STAT2, competing with JAK1 for receptor binding and thus inhibiting signal transduction."
| 1

sparser
"USP18 binds to IFNAR2 by competing with Jak1, thereby limits the activity of STATs and suppresses IFN response."

sparser
"Recently, it was also demonstrated that USP18 can directly interact with STAT2 to form a complex that inhibits IFN-I ligand binding to IFNAR2 ( xref , xref )."
USP18 inhibits IFNAR2.
| 1
USP18 inhibits IFNAR2. 1 / 3
| 1

reach
"In addition to its isopeptidase activity, USP18 negatively regulates type I and type III IFN signalling by blocking the IFNAR2 subunit of the interferon receptor ."
USP18 activates IFNAR2.
| 2
USP18 activates IFNAR2. 2 / 3
| 2

reach
"Even though type III IFN signaling requires JAK1, it is not affected by USP18 as USP18 specifically targets and binds IFNAR2 and not IFNLR (81)."

reach
"Even though type III IFN signaling requires JAK1, it is not affected by USP18 as USP18 specifically targets and binds IFNAR2 and not IFNLR."
USP18 decreases the amount of IFNAR2.
| 1
USP18 decreases the amount of IFNAR2. 1 / 1
| 1

reach
"USP18 was found to interact with the cytoplasmic domain of IFNAR2 and thus potentially down-regulate cell surface expression or binding affinity of IFNAR2."
IFNAR2 affects USP18
3 1 | 39 88
IFNAR2 binds USP18.
3 1 | 38 88
3 1 | 38 73

sparser
"The ISG ubiquitin specific peptidase 18 (USP18) binds to IFNAR2, preventing it from recruiting signal transducer and activator of transcription 1 (STAT1)."

sparser
"In STAT2-deficient cells, the USP18-mediated inhibition of type I interferon signalling was reduced and the interaction between IFNAR2 and USP18 was weakened pointing to an essential role of STAT2 in USP18-mediated inhibition of the type I interferon signalling pathway [58]."

reach
"Consistent with this, deletion of the STAT2 binding site on IFNAR2 reduced the binding of USP18 to IFNAR2 [50]."

reach
"These results established that USP18 independently interacts with IFNAR2 and STAT2."

sparser
"While it was first suggested that USP18 binding to IFNAR2 does not compete with ternary complex formation between IFNAR1, IFNAR2 and IFNα2 [56]."

sparser
"Furthermore, Usp18 functions in the type I IFN pathway by down-regulating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway independently of its isopeptidase activity through an interaction between Usp18 and the IFNAR2 subunit of the type I IFN receptor complex, while neither IFNAR1 nor IFNGR1 (type II IFN) receptor subunits were able to interact with Usp18 ( xref )."

reach
"We assume that recruitment of USP18 to IFNAR2 via STAT2 promotes the otherwise weak interaction of USP18 with a membrane proximal site of IFNAR2."

sparser
"Moreover, STAT2 can serve as an adaptor to bridge the interaction between USP18 and IFNAR2, which inhibits ligand binding to the receptor, resulting in decreased receptor dimerization and signaling ( xref )."

reach
"Gruber and colleagues confirmed this in coimmunoprecipitation experiments in transiently transfected U6A cells overexpressing WT or STAT2-R148Q and USP18, showing a reduced interaction between USP18 and IFNAR2 in the presence of STAT2-R148Q (Fig. 3) [57]."

sparser
"Specifically, murine USP18 can bind to human IFNAR2 and block type I IFN signaling by competitively interfering with Jak1 binding to the receptor [ xref ]."
| 10

sparser
"Mapping the STAT2 and USP18 binding to IFNAR2 by cell micropatterning of further deletions and mutations ( xref ) confirmed aa 418-444 of IFNAR2 as a minimal interaction site for STAT2 and USP18."

sparser
"Based on our previous report xref and the results presented above, USP18 interacts with both IFNAR2 and STAT2."

sparser
"Binding of STAT2 and USP18 to IFNAR2 is synergistic, in line with the previous observation that the STAT2-IFNAR2 interaction was strengthened by USP18 xref ."

sparser
"USP18 also interacts with IFNAR2 and STAT2 to block type I interferon signalling in a protease-independent manner."

sparser
"These results established that USP18 independently interacts with IFNAR2 and STAT2."

sparser
"USP18 binds STAT2 and IFNAR2, displacing JAK1 from the cytoplasmic domain of IFNAR2 and inducing a conformational change in the IFN-IFNAR1-IFNAR2 complex, leading to impaired signal transduction (left)."

sparser
"The reported interactions between USP18 and IFNAR2 as well as STAT2 remain to be characterised biochemically and structurally."

sparser
"More detailed analysis of the interaction dynamics of the STAT2IFNAR2 interaction in the presence of USP18 by FRAP ( xref ) revealed a dissociation rate constant of 0.015 ± 0.005 s −1 ."

sparser
"We next examined IFNAR2-independent interaction of STAT2 and USP18 in IFNAR2-deficient U5A cells by using cell micropatterning."

sparser
"Taken together, our data suggest that USP18 simultaneously interacts with IFNAR2 via STAT2 in the membrane distal region and directly in the membrane-proximal region ( xref )."
| 2

sparser
"Even though type III IFN signaling requires JAK1, it is not affected by USP18 as USP18 specifically targets and binds IFNAR2 and not IFNLR ( xref )."

sparser
"Even though type III IFN signaling requires JAK1, it is not affected by USP18 as USP18 specifically targets and binds IFNAR2 and not IFNLR (81)."
| 1

sparser
"USP18 can interact with IFNAR2 and STAT2, competing with JAK1 for receptor binding and thus inhibiting signal transduction."
| 1

sparser
"USP18 binds to IFNAR2 by competing with Jak1, thereby limits the activity of STATs and suppresses IFN response."

sparser
"Recently, it was also demonstrated that USP18 can directly interact with STAT2 to form a complex that inhibits IFN-I ligand binding to IFNAR2 ( xref , xref )."
IFNAR2 activates USP18.
| 1
IFNAR2 activates USP18. 1 / 1
| 1

reach
"Similarly, USP18, a ubiquitin-specific peptidase, is stimulated by JAK-STAT signaling and provides negative feedback to this pathway by binding IFNAR2, resulting in the promotion of viral replication [80]."
| PMC