STAT1

Protein STAT1

Identifiers
HUGO:STAT1
signal transducer and activator of transcription 1
HUGO:STAT1 hgnc_id:HGNC:11362 HGNC:11362 ENTREZ:6772 UNIPROT:P42224
signal transducer and activator of transcription 1, 91kDa
HUGO:STAT1 HGNC:11362 ENTREZ:6772 UNIPROT:P42224
"signal transducer and activator of transcription 1 91kD"

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / INHIBITING_CHECKPOINTS
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / INFLAMMATORY_SIGNALING_PATHWAYS
Cancer Associated Fibroblasts / CAF_INHIBITION_ANTITUMOR
EMT Senescence / EMT_REGULATORS
EMT Senescence / MITOCHONDRIA_OXIDATIVE_STRESS
EMT Senescence / SENESCENCE
Innate Immunity / IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS
Innate Immunity / IMMUNOSTIMULATORY_CYTOKINE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK

References
PMID:21263073 PMID:12796776
_INHIBITION_ANTITUMOR
CASCADE:IFNG
PMID:17559085, PMID:11134049
IFN-?? induced a direct interaction between activated STAT1?? and p300 in normal skin fibroblasts (Ghosh et al., 2001). Furthermore, ectopic expression of p300 overcame the inhibition by IFN-?? and rescued stimulation by TGF-??, suggesting that in response to IFN-??, activated STAT1?? and/or downstream factor(s) sequestered p300, preventing its recruitment to the transcriptional machinery and thereby inhibiting collagen gene transcription (Ghosh et al., 2001). Similarly, IFN-?? suppression of COL1A2 promoter activation by YB-1 also appears to involve p300 sequestration (Higashi et al., 2003).
PMID:12223527
Stat proteins 1 alpha, 3, 5A, 5B, and 6 are phosphorylated in response to IL-13.
PMID:19833085
STAT1 is activated downstream of IFNG by phosphorylation of tyrosine 701, translocates to the nucleus, binds to a regulatory DNA element termed gamma-activated sequence (GAS) and stimulates transcription of STAT1 target genes.
PMID:17689680
STAT1 acetilation inhibits its activity in macrophages.
PMID:12811837
TLR signaling can induces STAT1 phosphorylation via p38 and potentiate IFNG signaling.
PMID:14607900
FNG inhibits IL10 signalind via STAT1.
STAT1 overexpression prevents STAT3 homodimerization.
PMID:12193701, PMID:11830590
CD40 expression is upregulated by STAT1 downstream of INFG
and NF-kB downstream of TNF.
PMID:12193701
INFG upregulates TNFR1 and PIPK1 expression, probably via JAK/STAT1 pathway
because this expression is inhibited in presense of SOCS1.
PMID:15814715, PMID:18272812, PMID:17016554
STAT1 is involeved in immunosupresive activity of M2 macrophages and MDSC, probably downstream of IFNG.
PMID:21930765, PMID:8683106, PMID:12967644
IFNA and IFNB act via STAT1 pathway in DC and NK cells
PMID:25960930
Reduced IFN??-induced STAT-1 phosphorylation in Ser727 and CXCL10 secretion in NK cells derived from PKC-?????/??? mice
??11207245
I IFN receptor signaling regulates antigen cross-presentation to CD8(+) T cells. (), probably via upregulation of CD80, CD86, CD40, CD83 and MHC class II and CD11c,
PMID:17513775
Probably via STAT1(demondrtated for CD40 and CD11c PMID:14764699, and for CD40, CD80, CD86, and MHC II??

STAT1|pho|ace@INNATE_IMMUNE_CELL_Cytosol

References
in_re708( Innate Immunity ):
PMID:17689680
STAT1 acetilation inhibits its activity in macrophages.
PMID:19879327
Probably STAT1 is acetylated by CBP at the lysine residues K410 and K413.
in_re709( Innate Immunity ):
PMID:19833085, PMID:15699106, PMID:12138178, PMID:12270932
Inactivation of nuclear STAT1 occurs rapidly following binding to chromatin and activation of target gene transcription.
Subsequently STAT1 is dephosphorylated by phosphatases such as PTPN2 (TCP45) and PTPN11 (SHP2), and dephosphorylated STAT1
returns to cytoplasm, where it can potentially serve as the substrate for subsequent rounds of activation and inactivation.
PMID:19833085
Probably, acetylation of STAT1 on lysine residues 410 and 413 in the nucleus results in enhanced interaction with TCP45 (PTPN2) and increased dephosphorylation
in_re711( Innate Immunity ):
HDACs provide STAT1 deacetylation and activation.

STAT1|ace@INNATE_IMMUNE_CELL_Cytosol

References
in_re709( Innate Immunity ):
PMID:19833085, PMID:15699106, PMID:12138178, PMID:12270932
Inactivation of nuclear STAT1 occurs rapidly following binding to chromatin and activation of target gene transcription.
Subsequently STAT1 is dephosphorylated by phosphatases such as PTPN2 (TCP45) and PTPN11 (SHP2), and dephosphorylated STAT1
returns to cytoplasm, where it can potentially serve as the substrate for subsequent rounds of activation and inactivation.
PMID:19833085
Probably, acetylation of STAT1 on lysine residues 410 and 413 in the nucleus results in enhanced interaction with TCP45 (PTPN2) and increased dephosphorylation
in_re710( Innate Immunity ):
PMID:17689680
HDACs provide STAT1 deacetylation and activation.

STAT1|pho|active@INNATE_IMMUNE_CELL_Cytosol

References
in_re707( Innate Immunity ):
PMID:12811837
TLR signaling can induces STAT1 phosphorylation via p38 and potentiate IFNG signaling.
PMID:19833085
STAT1 is activated downstream of IFNG by phosphorylation of tyrosine 701, translocates to the nucleus, binds to a regulatory DNA element termed gamma-activated sequence (GAS) and stimulates transcription of STAT1 target genes.
in_re711( Innate Immunity ):
PMID:17689680
HDACs provide STAT1 deacetylation and activation.
in_re447( Innate Immunity ):
PMID:14607900
FNG inhibits IL10 signalind via STAT1.
STAT1 overexpression prevents STAT3 homodimerization.
in_re485( Innate Immunity ):
PMID:11875494
HMOX1 (HO1) mediates the inhibitory effect of IL10
on LPS-induced NOS2 (INOS) expression.
PMID:6357187, PMID:8871614
IL13 downregulates INOS activity via ILRA1/STAT6 pathway.
PMID:16127449
PPARG sumoilated by PIAS1/UbC9 prevents dissociation of the NCoR???HDAC3 complex fro promoters and
transrepresses NF-kB dependent expression NOS2, Ccl3, Ccl7, Cxcl10.
PMID:15644117, PMID:17260466
HMGB1 induces NO production probably via NFkB dependent upregulation of INOS expression.
STAT1 binds to INOS promoter and induces INOS expression and NO production downstream of IFNG in murine macrophages. Acetylation inhibits STAT1 binding to promotor.
PMID:11399519
STAT1, IRF1 and NF-kB interact with NOS2 promoter and cooperatively activate NOS2 expression in macrophages downstteam of IFNG.
PMID:23390297
MIF inhitits expression of M1 markers such as NOS2 (INOS).
PMID;PMID:20194441
HIF1 upregulates expression of INOS.
in_re708( Innate Immunity ):
STAT1 acetilation inhibits its activity in macrophages.
PMID:19879327
Probably STAT1 is acetylated by CBP at the lysine residues K410 and K413.
in_re712( Innate Immunity ):
PMID:19833085, PMID:15699106, PMID:15699106, PMID:15699106
Inactivation of nuclear STAT1 occurs rapidly following binding to chromatin and activation of target gene transcription.
Subsequently STAT1 is dephosphorylated by phosphatases such as PTPN2 (TCP45) and PTPN11 (SHP2), and dephosphorylated STAT1
returns to cytoplasm, where it can potentially serve as the substrate for subsequent rounds of activation and inactivation.
in_re714( Innate Immunity ):
PMID:11964313
INFG upregulates expression components of TLR signaling: MD2 (LY96) and MYD88.
in_re717( Innate Immunity ):
PMID:12433365
INFG induces SOCS1 expression in macrophages.
PMID:10820262
Probably IFNG induces SOCS1 expressiov via IRF1 upregulation downstream of STAT1
PMID:18345002
TNF induces IRF1 expression both through TNFR1 and TNFR2.
TNF induced IFNB expression through IRF1
in_re719( Innate Immunity ):
PMID:12433365, PMID:10485906
PMID:21097505
IL13 induces SOCS1 expression.
in_re721( Innate Immunity ):
PMID:12193701
INFG upregulates TNFR1 expression, probably via JAK/STAT1 pathway
because this expression is inhibited in presense of SOCS1.
in_re723( Innate Immunity ):
INFG upregulates RIPK1 expression, probably via JAK/STAT1 pathway
in_re729( Innate Immunity ):
PMID:14607933
TNF induces the association of STAT-1 and TNFR1 in a tyrosine phosphorylation-independent manner, and and this association attenuates TNF-alpha-mediated NF-kappaB activation but formation of the TNFR1:STAT-1?? complex is inhibited upon inclusion of IFNG . IFNG limits STAT-1 availability to the TNFR1 by depleting STAT from the cytoplasm, thus allowing for optimal NF-kappaB activation upon TNF ligation.
in_re1031( Innate Immunity ):
PMID:12907458
Bcl-3??? ???interacted with NF-??B p50,
both Bcl-3??? ???and p50??? ???were recruited to the TNF promoter,
BCL3??? ??? and??? ???p50??? ???NFkB recruitment to??? ???TNF ???promoter
prevents binding of??? ???p65/p50??? ???NFkB??? ???heterodimers
to??? ???TNF promotor and suppresses??? ???TNF ???expression
downstream of??? ???IL10.
PMID:17485448
Inhibition of??? ???NFkB signaling downstream of??? ???ABIN3??? ???
inhibits expression of??? ???IL8,??? ???IL6,??? ???TNF,??? ???IL12.
PMID:15465827
BCL3 forms complex with HDAC1 and
repression of the TNF promoter by BCL3
requires Histone Deacetylase Activity.
BCL3 inhibits expression of TNF.
HMOX1 (HO1) mediates IL-10-induced suppression of TNF production.
PMID:16878026, PMID:14660645, PMID:15644117, PMID:10952726
Increased TNF expression downstream of HMGB1 is regulated via MYD88 and probably NFkB.
PMID:10754326
Human TNF-alpha gene has binding sites for NF-kappa B. By transient transfection,
NF-kappa B p65 and p50 synergistically activated the TNF-alpha promoter.
Although both the kappa B1 and kappa B3 sites bound transcriptionally active NF-kappa B p50/p65 heterodimers, only the kappa B1 site contributed to down-regulation by NF-kappa B p50 homodimers.
PMID:17404308
CSF1 downregulates TNF, IL-23p19, IL-12p40 expression probably via induction of acomulation of p50 homodimer and inhibition of p65/p50 NF-kB signaling.
CSF2 upregulates expression of TNF, and have positive influence on IL12p70 (p40+p35), IL23 (p40+p19) expression, probably via induction rapid IkBa degradetion, RELA nuclear translocation and formation p65/p50 heterodimers provided induction of NFkB signaling.
PMID:7594497
TGFB1 and IL10 dowregulate expression of TNF.
MIF inhitits expression of M1 markers such as TNF.

STAT1@INNATE_IMMUNE_CELL_Cytosol

References
in_re710( Innate Immunity ):
PMID:17689680
HDACs provide STAT1 deacetylation and activation.
in_re712( Innate Immunity ):
PMID:19833085, PMID:15699106, PMID:15699106, PMID:15699106
Inactivation of nuclear STAT1 occurs rapidly following binding to chromatin and activation of target gene transcription.
Subsequently STAT1 is dephosphorylated by phosphatases such as PTPN2 (TCP45) and PTPN11 (SHP2), and dephosphorylated STAT1
returns to cytoplasm, where it can potentially serve as the substrate for subsequent rounds of activation and inactivation.
in_re707( Innate Immunity ):
PMID:12811837
TLR signaling can induces STAT1 phosphorylation via p38 and potentiate IFNG signaling.
PMID:19833085
STAT1 is activated downstream of IFNG by phosphorylation of tyrosine 701, translocates to the nucleus, binds to a regulatory DNA element termed gamma-activated sequence (GAS) and stimulates transcription of STAT1 target genes.

Modifications:
In compartment: INNATE_IMMUNE_CELL_Cytosol

STAT1@INNATE_IMMUNE_CELL_Cytosol
STAT1|ace@INNATE_IMMUNE_CELL_Cytosol
STAT1|pho|ace@INNATE_IMMUNE_CELL_Cytosol
STAT1|pho|active@INNATE_IMMUNE_CELL_Cytosol

Participates in complexes:
In compartment: INNATE_IMMUNE_CELL_Membrane

STAT1|pho:TNFR1*@INNATE_IMMUNE_CELL_Membrane

Participates in reactions:
As Reactant or Product:

As Catalyser: