IndraLab

Statements

USP18 affects STAT2
10 | 37 81
USP18 binds STAT2.
10 | 31 81
USP18 binds STAT2. 10 / 117
10 | 30 70
reach
"In this case, STAT2 was able to bind USP18, but USP18 interaction with IFNAR was impaired, leading to prolonged type I IFN signaling (49)."
37126806
sparser
"Since we identified the critical region for the USP18 interaction with STAT2 ( xref ), we also examined whether a peptide comprising USP18 aa 302-313 could have a similar effect as STAT2 CC/DB domains."
28165510
sparser
"In this case, the mutation, p.(R148Q), retained USP18-binding capacity, but the STAT2-USP18 dimer could not traffic to IFNAR2 (so as to displace JAK1), also resulting in enhanced IFN-I signalling."
36753016
sparser
"Taken together, our results demonstrate that, by interfering with the USP18-STAT2 interaction, USP18-mediated inhibition of the type I IFN signaling can be suppressed."
28165510
sparser
"3D modelling of the STAT2-USP18 heterodimer showed both the amino acid residues, A219 and R148, to localize to the interface between STAT2 and USP18 (Fig.  xref c), suggesting that the A219, like the R148, residue might play an essential role in mediating a STAT2-USP18 protein interaction."
36753016
reach
"MDA-MB-468 cells contain a single nucleotide polymorphism splice variant in STAT2, which may alter Type I IFN signal transduction and/or the scaffold interaction between USP18 and STAT2 required for IFNAR repression."
38632987
sparser
"Therefore, we aimed to explore the specific mechanism of signal inhibition by the STAT2-USP18 negative feedback interaction."
28165510
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
reach
"USP18 decreased IFNalpha binding to U6A cells only in the presence of full length STAT2 but not STAT2DeltaCC/DB (XREF_FIG), supporting the notion that interaction of STAT2 and USP18 is important for the type I IFN ligand-receptor binding."
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
STAT2 binds USP18 and IFNAR2. 8 / 8
| 8
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
"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
sparser
"We next examined IFNAR2-independent interaction of STAT2 and USP18 in IFNAR2-deficient U5A cells by using cell micropatterning."
28165510
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
"These results established that USP18 independently interacts with IFNAR2 and STAT2."
28165510
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
"The reported interactions between USP18 and IFNAR2 as well as STAT2 remain to be characterised biochemically and structurally."
30126853
IFNAR2 binds Interferon, USP18, and STAT2. 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 binds Interferon and STAT2. 1 / 1
| 1
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
USP18 binds FRAP and STAT2. 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
USP18 binds ISG15 and STAT2. 1 / 1
| 1
reach
"The I60N mutation has been shown to disrupt USP18-ISG15-STAT2 protein-protein interactions required for scaffold function in humans.17 50 51 To help clarify the structural basis of these changes, we modeled the USP18-ISG15-STAT2 complex with AlphaFold."
38632987
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.
| 2
USP18 leads to the dephosphorylation of STAT2. 2 / 2
| 2
reach
"The authors have demonstrated that: (i) infection of iMphs with HIV-1 induces USP18; (ii) depletion of USP18 with CRISPR/Cas9 increases iMph reactivity to IFNI, the phosphorylation of STAT1 and STAT2, the expression of IFN-stimulated genes and ultimately results in a significant restriction of HIV replication in iMphs."
35725499
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
USP18 activates STAT2.
| 1
USP18 activates STAT2. 1 / 2
| 1
reach
"It has been demonstrated that reconstitution of USP18 in ISG15-deficient cells alone restores STAT2 stability and limits viral growth."
39198221
USP18 phosphorylates STAT2.
| 1
USP18 phosphorylates STAT2. 1 / 1
| 1
reach
"USP18 iMacs had increased and sustained phosphorylated STAT1 and phosphorylated STAT2 (Fig. 7A)."
29437254
USP18 increases the amount of STAT2.
| 1
USP18 increases the amount of STAT2. 1 / 1
| 1
reach
"Increasing concentrations of USP18 ( Figure 6B lanes 3, 4 and 5) show a concentration-dependent displacement of NS5 from STAT2, suggesting that both proteins indeed compete for the same region of STAT2.Thus, we evaluated whether the presence of USP18 could restore STAT2 expression in ISG15 knockout cells during DV infection."
38384473
STAT2 affects USP18
10 | 33 81
STAT2 binds USP18.
10 | 31 81
USP18 binds STAT2. 10 / 117
10 | 30 70
reach
"In this case, STAT2 was able to bind USP18, but USP18 interaction with IFNAR was impaired, leading to prolonged type I IFN signaling (49)."
37126806
sparser
"Since we identified the critical region for the USP18 interaction with STAT2 ( xref ), we also examined whether a peptide comprising USP18 aa 302-313 could have a similar effect as STAT2 CC/DB domains."
28165510
sparser
"In this case, the mutation, p.(R148Q), retained USP18-binding capacity, but the STAT2-USP18 dimer could not traffic to IFNAR2 (so as to displace JAK1), also resulting in enhanced IFN-I signalling."
36753016
sparser
"Taken together, our results demonstrate that, by interfering with the USP18-STAT2 interaction, USP18-mediated inhibition of the type I IFN signaling can be suppressed."
28165510
sparser
"3D modelling of the STAT2-USP18 heterodimer showed both the amino acid residues, A219 and R148, to localize to the interface between STAT2 and USP18 (Fig.  xref c), suggesting that the A219, like the R148, residue might play an essential role in mediating a STAT2-USP18 protein interaction."
36753016
reach
"MDA-MB-468 cells contain a single nucleotide polymorphism splice variant in STAT2, which may alter Type I IFN signal transduction and/or the scaffold interaction between USP18 and STAT2 required for IFNAR repression."
38632987
sparser
"Therefore, we aimed to explore the specific mechanism of signal inhibition by the STAT2-USP18 negative feedback interaction."
28165510
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
reach
"USP18 decreased IFNalpha binding to U6A cells only in the presence of full length STAT2 but not STAT2DeltaCC/DB (XREF_FIG), supporting the notion that interaction of STAT2 and USP18 is important for the type I IFN ligand-receptor binding."
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
STAT2 binds USP18 and IFNAR2. 8 / 8
| 8
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
"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
sparser
"We next examined IFNAR2-independent interaction of STAT2 and USP18 in IFNAR2-deficient U5A cells by using cell micropatterning."
28165510
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
"These results established that USP18 independently interacts with IFNAR2 and STAT2."
28165510
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
"The reported interactions between USP18 and IFNAR2 as well as STAT2 remain to be characterised biochemically and structurally."
30126853
IFNAR2 binds Interferon, USP18, and STAT2. 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 binds Interferon and STAT2. 1 / 1
| 1
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
USP18 binds FRAP and STAT2. 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
USP18 binds ISG15 and STAT2. 1 / 1
| 1
reach
"The I60N mutation has been shown to disrupt USP18-ISG15-STAT2 protein-protein interactions required for scaffold function in humans.17 50 51 To help clarify the structural basis of these changes, we modeled the USP18-ISG15-STAT2 complex with AlphaFold."
38632987
STAT2 inhibits USP18.
| 2
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