TWIST1

Protein TWIST1 map

Identifiers
itwist homolog 1 (Drosophila)
HUGO:TWIST1 HGNC:12428 ENTREZ:7291 UNIPROT:Q15672 GENECARDS:TWIST1 KEGG:7291 ATLASONC:TWIST1ID44296ch7p21 WIKI:TWIST1

Maps_Modules
 EMT  map  / EMT_REGULATORS  map

References
PMID:15640618
Twist induces an epithelial-mesenchymal transition to facilitate tumor metastasis.

TWIST1@Nucleus

References
e_re13( EMT  map ):
PMID:18297062
TWIST is a downstream target of HIF-1
Hypoxia or HIF-1 induces EMT through the direct activation of TWIST expression
e_re1186( EMT  map ):
PMID:21502402
Phosphorylation of serine 68 of Twist1 stabilizes Twist1 protein and promotes breast cancer cell invasiveness.
Twist1 can be phosphorylated in vitro at Serin 68 by MAPKs (p38MAPKs, JNKs, ERK1/2)
This phosphorylation is required for Twist1 protein stability.
pSer 68 stabilizes Twist1 by protecting Twist1 from ubiquitination
Ser 68 phosphorylation is required for Twist1- promoted EMT and breast cancer cell invasion

TWIST1|​S68_pho@Nucleus

References
e_re1186( EMT  map ):
PMID:21502402
Phosphorylation of serine 68 of Twist1 stabilizes Twist1 protein and promotes breast cancer cell invasiveness.
Twist1 can be phosphorylated in vitro at Serin 68 by MAPKs (p38MAPKs, JNKs, ERK1/2)
This phosphorylation is required for Twist1 protein stability.
pSer 68 stabilizes Twist1 by protecting Twist1 from ubiquitination
Ser 68 phosphorylation is required for Twist1- promoted EMT and breast cancer cell invasion
e_re2( EMT  map ):
PMID:20731704
PMID:21317430
In NMuMG cells treated with TGFB1 Snail1 RNA and protein are induced 1 h after addition of the cytokine preceding Zeb1 up-regulation that requires 6–8 h.
Zeb1 gene expression is caused by increased RNA levels but also by enhanced protein stability and is markedly dependent on Snail1 because depletion of this protein prevents Zeb1 protein and RNA up-regulation
PMID:22406545
TGFB can activate both SNAI1 and SNAI2 and thus promote EMT via both SMAD-dependent and -independent pathways
PMID:14623871
Activation of Slug (SNAI2) by two mechanisms:
-transcriptional activation of Slug by the CTNNB1and TCF/LEF complex
-activation of the ERK pathway.
When adherens junctions are established in dense cultures, ErbB1/2 and the ERK pathway become inactive, CTNNB1 is localized at adherens junctions, Slug expression is reduced, and E-cadherin transcription is induced.
Antibody-mediated disruption of adherens junctions led to nuclear CTNNB1 localization and enhanced beta-catenin signaling, induction of Slug and inhibition of E-cadherin expression.
PMID:17093497
PMID:12490555
Snail1 induces Snail2 transcription.
Snail is able to induce the expression of Slug and all other neural crest markers (Zic5, FoxD3, Twist and Ets1)
PMID:16510505
Snail2 activates the Snail2 promoter
PMID:21199805
Twist1 binds to an E-box on the proximate Snail2 promoter to induce its transcription.
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
PMID:17550342
Activation of KIT by binding to KITLG induces SNAI2 expression
e_re4( EMT  map ):
PMID:19208835
TCF8 (ZEB1) is up-regulated in endothelial cells during angiogenesis, acting as a negative regulator.
Snail1 controls Zeb1 expression at multiple levels and acts cooperatively with Twist in the ZEB1 gene transcription induction
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_re51( EMT  map ):
PMID:17987801
Expression of Twist positively correlated with up-regulation of VEGF and N-cadherin in hepatocellular carcinoma
e_re660( EMT  map ):
PMID:15980428
PMID:19284610
The associations between Cx43 and ZO-1 and ZO-2 proteins were shown to be under cell-cycle stage-specific control.
Connexin 43 interacts preferentially with ZO-1 during G0 stage, whereas the interaction with ZO-2 is approximately the same during the various stages
e_re1195( EMT  map ):
PMID:22945800
PMID:18297062
TWIST1 associates with enhanced tumor microvessel vasculature (angiogenesis)
TWIST1 associates with VEGF expression in hepatocarcinomas
e_re1197( EMT  map ):
PMID:21919891
PMID:21733352
Direct activation of Bmi1 expression by Twist1 using transient transfection.
PMID:20818389
Twist1 directly activates BMI1 transcription by binding to the E-box in intron 1 of the BMI1 gene.
SNAI2 induces BMI1 expression
e_re1204( EMT  map ):
Physical interaction between BMI1 and TWIST1
E-Cadherin repression by cooperative BMI1 and TWIST1
p16INK4A repression by cooperative BMI1 and TWIST1
e_re1213( EMT  map ):
PMID:15140942
Phosphorylations on p53 prevent its binding to MDM2.
PMID:15574337
S186 phosphorylation of MDM2 by AKT favors the binding of MDM2 to p53 and its following degradation.
PMID:19336515
TWIST1 physically promotes interaction between p53 and MDM2
e_re1222( EMT  map ):
PMID:17537911
Ectopic expression of any one of (Twist, Snail, or Goosecoid) led to induction of both FOXC2 mRNA and protein expression.
e_re1302( EMT  map ):
PMID:17332325
TWIST1 binds to E-box elements on AKT2 promoter and enhanced its transcriptional activity
e_re1307( EMT  map ):
TWIST downregulates E-Cadherin and beta-Catenin


Modifications:
In compartment: Nucleus
  1. TWIST1@Nucleus map

  2. TWIST1|​S68_pho@Nucleus map

Participates in complexes:
In compartment: Nucleus

  1. BMI1:​TWIST1|​S68_pho@Nucleus map

Participates in reactions:
As Reactant or Product:

  1. TWIST1@Nucleus map map TWIST1|​S68_pho@Nucleus map

  2. TWIST1|​S68_pho@Nucleus map map Angiogenesis@Nucleus map
  3. TWIST1|​S68_pho@Nucleus map + BMI1@Nucleus map map BMI1:​TWIST1|​S68_pho@Nucleus map
  4. rTWIST1@Nucleus map map TWIST1@Nucleus map
  5. TWIST1@Nucleus map map degraded

As Catalyser:

  1. gBMI1@Nucleus map map rBMI1@Nucleus map

  2. gCDKN2A@Nucleus map map rp16INK4A*@Nucleus map
  3. p53*@Nucleus map + MDM2|​S186_pho@Nucleus map map MDM2|​S186_pho:​p53*@Nucleus map
  4. gFOXC2@Nucleus map map rFOXC2@Nucleus map
  5. rFOXC2@Nucleus map map FOXC2@Nucleus map
  6. gAKT2@Nucleus map map rAKT2@Nucleus map
  7. g_beta_-Catenin*@Nucleus map map r_beta_-Catenin*@Nucleus map
  8. gSNAI2@Nucleus map map rSNAI2@Nucleus map
  9. gVEGFA@Nucleus map map rVEGFA@Nucleus map
  10. gE-Cadherin*@Nucleus map map rE-Cadherin*@Nucleus map
  11. gZEB1@Nucleus map map rZEB1@Nucleus map
  12. gN-Cadherin*@Nucleus map map rN-Cadherin*@Nucleus map
  13. GJA1:​ZO2*@Cytoplasm map map Proliferation@Cytoplasm map

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