IndraLab

Statements

USP18 affects STAT2
| 22 61
USP18 binds STAT2.
| 20 61
STAT2 binds USP18. 10 / 73
| 20 46
sparser
"Whilst this STAT2:USP18 interaction has been shown to be essential for negative regulation of type I IFN signaling in vitro ( xref ), its significance in vivo has not previously been examined."
31836668
sparser
"This structural insight may be relevant to efforts to therapeutically interfere with the STAT2:USP18 interaction in order to promote the antiviral action of IFNs."
31836668
reach
"Based on our previous report 21 and the results presented above, USP18 interacts with both IFNAR2 and STAT2."
28165510
reach
"Together, these results establish that the interaction between USP18 and STAT2 mediates the inhibitory effect of USP18 on type I IFN receptor assembly and signaling."
28165510
sparser
"Consistent with our suspicion that this might impair the STAT2:USP18 interaction through electrostatic or steric hindrance, co-immunoprecipitation experiments in U6A cells stably expressing WT or STAT2 R148W demonstrated a significant reduction of USP18 pull-down with STAT2 R148W compared to WT ( xref ), providing a molecular mechanism for the USP18 insensitivity of patient cells."
31836668
reach
"These results established that the interaction of USP18 and STAT2 is responsible for recruitment of USP18 to IFNAR2 and is critical for the negative effect of USP18 on type I IFN induced JAK1 phosphorylation (XREF_FIG), which is upstream of type I IFN induced STAT1 activation."
28165510
sparser
"To explore whether the STAT2-USP18 interaction is important for the effect of USP18 on ligand binding and ternary complex formation, ligand binding assays in U6A cells were performed."
28165510
sparser
"In absence of STAT2 binding of USP18 was weakened such as no significant recruitment of USP18 to micropatterned IFNAR2 was detectable in this experimental system."
28165510
sparser
"To quantify the interaction between STAT2 and USP18 in live cells, a cell micropatterning approach for spatially controlled immobilization of bait proteins in the plasma membrane via the HaloTag xref was employed ( xref )."
28165510
reach
"Together, these different approaches clearly established that STAT2 directly binds to USP18."
28165510
STAT2 binds USP18 and IFNAR2. 10 / 10
| 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."
28165510
sparser
"Based on our previous report xref and the results presented above, USP18 interacts with both IFNAR2 and STAT2."
28165510
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 ."
28165510
sparser
"USP18 also interacts with IFNAR2 and STAT2 to block type I interferon signalling in a protease-independent manner."
30126853
sparser
"These results established that USP18 independently interacts with IFNAR2 and STAT2."
28165510
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)."
34448086
sparser
"The reported interactions between USP18 and IFNAR2 as well as STAT2 remain to be characterised biochemically and structurally."
30126853
sparser
"More detailed analysis of the interaction dynamics of the STAT2–IFNAR2 interaction in the presence of USP18 by FRAP ( xref ) revealed a dissociation rate constant of 0.015 ± 0.005 s −1 ."
25385185
sparser
"We next examined IFNAR2-independent interaction of STAT2 and USP18 in IFNAR2-deficient U5A cells by using cell micropatterning."
28165510
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 )."
28165510
Interferon binds STAT2 and USP18. 2 / 2
| 2
sparser
"Two siblings with early onset autoinflammatory disease with neurological features and elevated IFN signature were additionally described with a homozygous missense mutation in STAT2 resulting in gain of activity due to the inability of mutant STAT2 to interact with the STAT2-dependent negative regulator of interferon activity, USP18 [107]."
34258050
sparser
"Two siblings with early onset autoinflammatory disease with neurological features and elevated IFN signature were additionally described with a homozygous missense mutation in STAT2 resulting in gain of activity due to the inability of mutant STAT2 to interact with the STAT2-dependent negative regulator of interferon activity, USP18 [ xref ]."
34258050
STAT2 binds USP18, IFNAR2, and JAK1. 1 / 1
| 1
sparser
"USP18 can interact with IFNAR2 and STAT2, competing with JAK1 for receptor binding and thus inhibiting signal transduction."
32039148
STAT2 binds USP18 and MTOR. 1 / 1
| 1
sparser
"Monitoring the exchange kinetics of intracellular USP18 bound to micropatterned STAT2 by FRAP ( xref ) yielded a mean interaction lifetime of τ: 53 s ± 28 s (8 cells analyzed)."
28165510
Interferon binds STAT2, USP18, and IFNAR2. 1 / 1
| 1
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 )."
30266866
USP18 inhibits STAT2.
| 1
USP18 inhibits STAT2. 1 / 2
| 1
reach
"XREF_BIBR, XREF_BIBR To asses whether STAT1 or STAT2, which are both upregulated by USP18 inhibition (XREF_FIG), are implicated in the upregulation of Bim, DP5 and PUMA mRNA expression in USP18 silenced cells, we inhibited in parallel USP18 and STAT1 or STAT2 in INS-1E cells by use of specific siRNAs."
23152055
USP18 dephosphorylates STAT2.
| 1
USP18 leads to the dephosphorylation of STAT2. 1 / 1
| 1
reach
"USP18 acts to prevent JAK1 from binding to IFN-I receptor and hence arrests phosphorylation of STAT1 and STAT2, essential components of the transcription factor complex that induces ISGs."
32402279
STAT2 affects USP18
| 23 61
STAT2 binds USP18.
| 20 61
STAT2 binds USP18. 10 / 73
| 20 46
sparser
"Whilst this STAT2:USP18 interaction has been shown to be essential for negative regulation of type I IFN signaling in vitro ( xref ), its significance in vivo has not previously been examined."
31836668
sparser
"This structural insight may be relevant to efforts to therapeutically interfere with the STAT2:USP18 interaction in order to promote the antiviral action of IFNs."
31836668
reach
"Based on our previous report 21 and the results presented above, USP18 interacts with both IFNAR2 and STAT2."
28165510
reach
"Together, these results establish that the interaction between USP18 and STAT2 mediates the inhibitory effect of USP18 on type I IFN receptor assembly and signaling."
28165510
sparser
"Consistent with our suspicion that this might impair the STAT2:USP18 interaction through electrostatic or steric hindrance, co-immunoprecipitation experiments in U6A cells stably expressing WT or STAT2 R148W demonstrated a significant reduction of USP18 pull-down with STAT2 R148W compared to WT ( xref ), providing a molecular mechanism for the USP18 insensitivity of patient cells."
31836668
reach
"These results established that the interaction of USP18 and STAT2 is responsible for recruitment of USP18 to IFNAR2 and is critical for the negative effect of USP18 on type I IFN induced JAK1 phosphorylation (XREF_FIG), which is upstream of type I IFN induced STAT1 activation."
28165510
sparser
"To explore whether the STAT2-USP18 interaction is important for the effect of USP18 on ligand binding and ternary complex formation, ligand binding assays in U6A cells were performed."
28165510
sparser
"In absence of STAT2 binding of USP18 was weakened such as no significant recruitment of USP18 to micropatterned IFNAR2 was detectable in this experimental system."
28165510
sparser
"To quantify the interaction between STAT2 and USP18 in live cells, a cell micropatterning approach for spatially controlled immobilization of bait proteins in the plasma membrane via the HaloTag xref was employed ( xref )."
28165510
reach
"Together, these different approaches clearly established that STAT2 directly binds to USP18."
28165510
STAT2 binds USP18 and IFNAR2. 10 / 10
| 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."
28165510
sparser
"Based on our previous report xref and the results presented above, USP18 interacts with both IFNAR2 and STAT2."
28165510
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 ."
28165510
sparser
"USP18 also interacts with IFNAR2 and STAT2 to block type I interferon signalling in a protease-independent manner."
30126853
sparser
"These results established that USP18 independently interacts with IFNAR2 and STAT2."
28165510
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)."
34448086
sparser
"The reported interactions between USP18 and IFNAR2 as well as STAT2 remain to be characterised biochemically and structurally."
30126853
sparser
"More detailed analysis of the interaction dynamics of the STAT2–IFNAR2 interaction in the presence of USP18 by FRAP ( xref ) revealed a dissociation rate constant of 0.015 ± 0.005 s −1 ."
25385185
sparser
"We next examined IFNAR2-independent interaction of STAT2 and USP18 in IFNAR2-deficient U5A cells by using cell micropatterning."
28165510
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 )."
28165510
Interferon binds STAT2 and USP18. 2 / 2
| 2
sparser
"Two siblings with early onset autoinflammatory disease with neurological features and elevated IFN signature were additionally described with a homozygous missense mutation in STAT2 resulting in gain of activity due to the inability of mutant STAT2 to interact with the STAT2-dependent negative regulator of interferon activity, USP18 [107]."
34258050
sparser
"Two siblings with early onset autoinflammatory disease with neurological features and elevated IFN signature were additionally described with a homozygous missense mutation in STAT2 resulting in gain of activity due to the inability of mutant STAT2 to interact with the STAT2-dependent negative regulator of interferon activity, USP18 [ xref ]."
34258050
STAT2 binds USP18, IFNAR2, and JAK1. 1 / 1
| 1
sparser
"USP18 can interact with IFNAR2 and STAT2, competing with JAK1 for receptor binding and thus inhibiting signal transduction."
32039148
STAT2 binds USP18 and MTOR. 1 / 1
| 1
sparser
"Monitoring the exchange kinetics of intracellular USP18 bound to micropatterned STAT2 by FRAP ( xref ) yielded a mean interaction lifetime of τ: 53 s ± 28 s (8 cells analyzed)."
28165510
Interferon binds STAT2, USP18, and IFNAR2. 1 / 1
| 1
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 )."
30266866
STAT2 inhibits USP18.
| 3
STAT2 inhibits USP18. 2 / 2
| 2
reach
"In addition, STAT2 CC/DB 3A, but not STAT2 CC/DB, partially blocked the effect of USP18 on transcription of ISGs, such as GBP1 and IFIT1 (XREF_FIG and XREF_SUPPLEMENTARY)."
28165510
reach
"Additionally, a homozygous miss-sense mutation in STAT2 results in failure to appropriately traffic USP18 to IFNAR2 and prevents USP18 from negatively regulating responses to IFN-Is, which leads to infant death from autoinflammation disease (168)."
34707613
STAT2-R148Q inhibits USP18. 1 / 1
| 1
reach
"Rather, the STAT2 R148Q variant is a GOF because it fails to appropriately traffic USP18 to IFNAR2, thereby preventing USP18 from negatively regulating responses to IFN-I."
32092142