BMI1

Protein BMI1 map

Identifiers
BMI1 polycomb ring finger oncogene
“B lymphoma Mo-MLV insertion region 1 homolog (mouse)”, PCGF4, “polycomb group ring finger 4″
HUGO:BMI1 HGNC:1066 ENTREZ:648 UNIPROT:P35226 GENECARDS:BMI1 KEGG:648 ATLASONC:BMI1ID807ch10p12 WIKI:BMI1

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 DNA repair  map  / G1_S_CHECKPOINT  map

References
PMID:22796940
The silencing of E-cadherin expression by hypermethylation is a common event in cancer.
DNMTs target cytosine residues in CpG dinucleotides for methylation and have been identified in the repression of E-cadherin in normal and pathological contexts
such as colorectal cancer, gastric cancer and hepatocellular carcinomas.
Multiple signaling pathways involved in EMT and tumorigenesis activate DNMTs, e.g., ras43 and TGF-b.
DNMTs bind several histone remodeling enzymes, such as Sirtuin and G9a.
However, SNAI1 has been shown to be linked to DNMT1, notably in association with G9a and Suv39H1.
Cooperation between Polycomb proteins and EMT-inducing transcription factors.
The polycomb proteins are part of repressor complexes that inhibit gene expression through chromatin remodeling.
The polycomb repressive complex 2 (PRC2) recruits PRC1 after chromatin methylation at H3K27 through enhancer of EZH2, a histone H3 lysine-27-specific methyltransferase.
Both, PRC1 and PRC2 have been shown to interact with SNAI1 and TWIST1 to promote EMT.
SNAI1 is stabilized through its interaction with the PRC1 component BMI1 and interacts with EZH2 and Suz12 to repress CDH1 expression.
Interestingly, EZH2 also participates in TGFb1 signaling, a potent inducer of EMT.
BMI-1 can also interact with TWIST to induce EMT.
Repression of E-cadherin by SNAI1/TWIST1 involves the recruitment of histone remodeling proteins to the promoter, where SNAI1 interacts with histone deacetylase HDAC1 and HDAC2.
The intricate interactions of EMT-inducing transcription factors and chromatin remodeling complexes PRC1 and PRC2 may offer novel approaches to control EMT and thus cell adhesion in cancer cells via a plethora of new drug, such as HDACs and DNMT inhibitors.
PMID:17936558, PMID:21678481, PMID:21685941, PMID:21383063

BMI1@Nucleus

References
e_re1204( EMT  map ):
PMID:20818389
Physical interaction between BMI1 and TWIST1
E-Cadherin repression by cooperative BMI1 and TWIST1
p16INK4A repression by cooperative BMI1 and TWIST1

BMI1@Cytoplasm

References
e_re1198( EMT  map ):
PMID:19935649
Protein expression of Bmi1, Sox2, p63 was reduced after ZEB1 knockdown.
ZEB1 knockdown not only resulted in reduced invasion and metastasis, but also in reduced tumorigenicity.
ZEB1 is also necessary for the self-renewing capacity.
ZEB1 is crucial for drug resistance in pancreatic cancer cells. This supports data showing that EMT activators (Twist and Snail) confer anti-apoptotic properties

BMI1|​unk@default

References
d_re399( DNA repair  map ):
Repression of p15INK4b expression by Myc through association with Miz-1:
PMID:9308237, PMID:11283613
Repression of pINK expression by BMI1:
PMID:17936558


Modifications:
In compartment: Cytoplasm
  1. BMI1@Cytoplasm map

In compartment: Nucleus

  1. BMI1@Nucleus map

In compartment: default

  1. BMI1@default map

  2. BMI1|​unk@default map

Participates in complexes:
In compartment: Nucleus

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

Participates in reactions:
As Reactant or Product:

  1. BMI1|​unk@default map map BMI1@default map

  2. BMI1@default map map BMI1|​unk@default map
  3. BMI1@Cytoplasm map map BMI1@Nucleus map
  4. rBMI1@Nucleus map map BMI1@Cytoplasm map
  5. TWIST1|​S68_pho@Nucleus map + BMI1@Nucleus map map BMI1:​TWIST1|​S68_pho@Nucleus map

As Catalyser:

  1. gINK4*@default map map rINK4*@default map

  2. gCDKN2A@Nucleus map map rp16INK4A*@Nucleus map
  3. gE-Cadherin*@Nucleus map map rE-Cadherin*@Nucleus map

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