TWIST1

Protein TWIST1

Identifiers
itwist homolog 1 (Drosophila)
HUGO:TWIST1 HGNC:12428, ENTREZ:7291, UNIPROT:Q15672, GENECARDS:GC07M019121

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS

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

TWIST1@Nucleus

References
em_emtc_emtc_re13( EMT Senescence ):
PMID:18297062
TWIST is a downstream target of HIF-1
Hypoxia or HIF-1 induces EMT through the direct activation of TWIST expression
em_emtc_emtc_re1186( EMT Senescence ):
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
em_emtc_emtc_re1186( EMT Senescence ):
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
em_emtc_emtc_re2( EMT Senescence ):
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
em_emtc_emtc_re4( EMT Senescence ):
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
em_emtc_emtc_re24( EMT Senescence ):
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
Expression of Twist positively correlated with up-regulation of VEGF and N-cadherin in hepatocellular carcinoma
PMID:16716598
VEGF transcriptional expression is induced by hypoxia in different cell types under action of y HIF1
em_emtc_emtc_re660( EMT Senescence ):
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
em_emtc_emtc_re1195( EMT Senescence ):
PMID:22945800
PMID:18297062
PMID:17987801
TWIST1 associates with enhanced tumor microvessel vasculature (angiogenesis)
TWIST1 associates with VEGF expression in hepatocarcinomas
em_emtc_emtc_re1197( EMT Senescence ):
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
PMID:11283614
Myc: an ubiquitous mediator of cell growth and proliferation
Myc can both activate and repress transcription, depending on the nature of associated factors
TGFB downregulates Myc to cause cell cycle arrest.
TGFB activates p15INK4B and/or p21CIP1 (inhibitor of CDKs) ==> CDK inhibition by TGFB
TGFB downregulates cdc25A (a phosphatase, activator of CDKs) ==> CDK inhibition by TGFB
PMID:2191300
Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter.
PMID??:28536364
c-myc is transcriptionally upregulated by NF-??B
PMID:20027199
MYC induces DNA damage throuh an increase in ROS production, innapropriate DNA synthesis and abrogation of DNA repair
PMID:20713526
MYC supress the activity of anti-apoptotic BCL2 and BCLXL (BCL2L1) genes
PMID??:20713526
MYC in complex with CDK2 alone inhibit senescence through the inhibition of p16 and p21 expression as well as TERT and BMI1 expression increase. MYC in complex with CDK2 and p27KIP1 induces senescence through the expression increase of p16 and p21 as well as TERT and BMI1 expression decrease. WRN inhibit MYC induced senescence.
PMID??: PMID:17055429
MYC stimulate P53 and ARF
em_emtc_emtc_re1204( EMT Senescence ):
Physical interaction between BMI1 and TWIST1
E-Cadherin repression by cooperative BMI1 and TWIST1
p16INK4A repression by cooperative BMI1 and TWIST1
em_emtc_emtc_re1213( EMT Senescence ):
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
em_emtc_emtc_re1222( EMT Senescence ):
PMID:17537911
Ectopic expression of any one of (Twist, Snail, or Goosecoid) led to induction of both FOXC2 mRNA and protein expression.
em_emtc_emtc_re1302( EMT Senescence ):
PMID:17332325
TWIST1 binds to E-box elements on AKT2 promoter and enhanced its transcriptional activity
em_emtc_emtc_re1307( EMT Senescence ):
TWIST downregulates E-Cadherin and beta-Catenin

Modifications:
In compartment: Nucleus

TWIST1@Nucleus
TWIST1|S68_pho@Nucleus

Participates in complexes:
In compartment: Nucleus

BMI1:TWIST1|S68_pho@Nucleus

Participates in reactions:
As Reactant or Product:

As Catalyser: