STAT3

Protein STAT3 map

Identifiers
signal transducer and activator of transcription 3 (acute-phase response factor)
HUGO:STAT3 HGNC:11364 ENTREZ:6774 UNIPROT:P40763 GENECARDS:STAT3 REACTOME:403956 KEGG:6774 ATLASONC:STAT3ID444 WIKI:STAT3

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Apoptosis  map  / APOPTOSIS_GENES  map
 Apoptosis  map  / HIF1  map
 Apoptosis  map  / MITOCH_METABOLISM  map

STAT3|​pho|​active@Nucleus

References
e_re6( EMT  map ):
PMID:21883379
PMID:18297062
TWIST is a downstream target of HIF-1
Hypoxia or HIF-1 induces EMT through the direct activation of TWIST expression
PMID:19412634
Twist is a target of Snail1
PMID:22945800
PMID:21317430
Expression of Twist1 and Snail1 are mutually dependent
Knock-down of Snail1 downregulates Twist1 protein and mRNA
Knock- down of Twist1 interferes with TGFb-mediated induction of Snail1.
PMID:22006115
Alternatively, it has also been reported that Snail1 transcriptionally represses Twist1
PMID:16831886
PMID:18832382
HMGA2 directly binds to the SNAIL1 promoter and acts as a transcriptional regulator of SNAIL1 expression.
HMGA2 cooperates with SMAD3 and SMAD4 to execute a dramatic super-induction of the SNAIL1 promoter.
Same results were obtained with SNAI2, ZEB1, ZEB2 and TWIST1
HMGA2 cooperates with TGFB1 signaling to represse ID2 transcriptomal expression
e_re24( EMT  map ):
PMID:13130303
Keratin-14, 18, 19, Vimentin are putative direct HIF1 target genes
http://www.omicsonline.org/1948-5956/JCST-03-035.php
Genes induced by HIF-1 in cancer cells include KRT-14, 18, 19, Vimentin, VEGF
PMID:9278421
HIF1 target genes include TGFB3, VEGF
PMID:7768934
VEGF is induced by hypoxia in a HIF1-dependent way
PMID:11528470
Prokinecticin 1 (EG-VEGF) is induced by hypoxia through a potential HIF1-dependent mechanism indicates that this gene is in the same homeostatic cascade as VEGF, Flt1 and erythropoietinPMID:17987801 PMID:16716598
e_re1123( EMT  map ):
PMID:15810077
Beta-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: relationships with carcinogenesis and metastasis.
PMID:22943793
Role of TGFB in regulation of cell cycle:
Physiologically, TGFB is a potent inhibitor of cell cycle.
It induces expression of p15INK4B and represses expression of c-Myc
Low levels of c-Myc allows TGFB to induce p15INK4B and p21CIP1 transcription

STAT3|​S727_pho@Mitochondrial inner membrane

References
a_re70( Apoptosis  map ):
PMID:19131594
in mouse liver, in mouse pro-B cells, STAT3 is found in mitochondria
mitochondrial STAT3 interacts with NDUFA13
mitochondrial STAT3 necessary for proper activity of complexes I and II of the electron transport chain
STAT3 in mitochondria is preferentially phosphorylated on S727

STAT3|​S727_pho@Cytoplasm

References
a_re386( Apoptosis  map ):
PMID:10973499
in vitro reconstitution of the E3-ligase activity, with VHL, elonginB/C, RBX1,CUL2
PMID:18985005
in COS monkey kidney cells and Caki-I human renal carcinoma cells, inhibition of VHL-mediated HIF1A ubiquitinylation and degradation by ectopically expressed constitutively active STAT3

STAT3|​S727_unk@Nucleus

References
a_re106( Apoptosis  map ):
PMID:18208354
TP53 downregulates the activity of the MCL1 gene promoter in Hela and HEK293
mainly through an unkown mechanism. Critical importance of the -41 to +16 region that correspond to TATA-BP and other basal transcription factors binding
also through down regulation of Sp1
PMID:19808698
in MV4-11 cells, a human biphenotypic B myelomonocytic leukemia that displays FLT3-ITD mutation (constitutive FLT3 signalling), STAT5* siRNA prevents MCL1 expression
PMID:11160159
in large granular lymphocyte high STAT3 activity correlates with MCL1 expression, AG-490 JAK inhibitors induce apoptosis and decreases MCL1 expression.
in NIH3T3, upon v-src, STAT3 dependent expression of MCL1


Modifications:
In compartment: Cytoplasm
  1. STAT3@Cytoplasm map

  2. STAT3|​S727_pho@Cytoplasm map
  3. STAT3|​pho|​active@Cytoplasm map

In compartment: Mitochondrial inner membrane

  1. STAT3|​S727_pho@Mitochondrial inner membrane map

In compartment: Nucleus

  1. STAT3|​S727_unk@Nucleus map

  2. STAT3|​pho|​active@Nucleus map

In compartment: default

  1. STAT3|​Ser727_pho@default map

Participates in complexes:
In compartment: default

  1. CDK5:​EME1:​STAT3|​Ser727_pho@default map

Participates in reactions:
As Reactant or Product:

  1. EME1@default map + STAT3|​Ser727_pho@default map + CDK5@default map map CDK5:​EME1:​STAT3|​Ser727_pho@default map

  2. STAT family*@Cytoplasm map map STAT3@Cytoplasm map
  3. STAT3@Cytoplasm map map STAT3|​pho|​active@Cytoplasm map
  4. STAT family*|​pho|​active@Cytoplasm map map STAT3|​pho|​active@Cytoplasm map
  5. STAT3|​pho|​active@Cytoplasm map map STAT3|​pho|​active@Nucleus map

As Catalyser:

  1. gMCL1@Nucleus map map rMCL1@Nucleus map

  2. HIF1A|​P564_hyd@Cytoplasm map map HIF1A|​ubi|​P564_hyd@Cytoplasm map
  3. ubiquinone@Mitochondrial inner membrane map + H+@Mitochondrial Matrix map + NADH@Mitochondrial Matrix map map ubiquinol@Mitochondrial inner membrane map + H+@Mitochondrial intermembrane space map + NAD_super_+_endsuper_@Mitochondrial Matrix map
  4. gHR_DNA_st5*@Nucleus map map gHR_DNA_st6*@Nucleus map
  5. gMYC@Nucleus map map rMYC@Nucleus map
  6. gTIMP1@Nucleus map map rTIMP1@Nucleus map
  7. gFOS@Nucleus map map rFOS@Nucleus map
  8. gVEGFA@Nucleus map map rVEGFA@Nucleus map
  9. gTWIST1@Nucleus map map rTWIST1@Nucleus map

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