HDAC2

Protein HDAC2 map

Identifiers
histone deacetylase 2
HUGO:HDAC2 HGNC:4853 ENTREZ:3066 UNIPROT:Q92769 GENECARDS:HDAC2 REACTOME:56410 KEGG:3066 ATLASONC:HDAC2ID40803ch6q22 WIKI:HDAC2

Maps_Modules
 EMT  map  / EMT_REGULATORS  map
 Survival  map  / WNT_NON_CANONICAL  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.

HDAC2@Nucleus

References
e_re1184( EMT  map ):
PMID:22796940
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.
PMID:14673164
Snail interacts in vivo with the E-cadherin promoter and recruits HDAC activity.
Interaction between Snail, HDAC1 and HDAC2, and the corepressor Sin3A is dependent on the SNAG domain of Snail, indicating that the Snail transcription factor mediates the repression by recruitment of chromatin-modifying activities, forming a multimolecular complex to repress E-cadherin expression.
e_re1185( EMT  map ):
PMID:21685935
EZH2 supports carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1 and HDAC2 and Snail to inhibit E-cadherin.


Modifications:
In compartment: Nucleus
  1. HDAC2@Nucleus map

Participates in complexes:
In compartment: Nucleus

  1. CBF1*:​CIR1:​HDAC2:​SIN3A@Nucleus map

  2. EZH2:​HDAC1:​HDAC2:​SNAI1@Nucleus map
  3. HDAC1:​HDAC2:​SIN3A:​SNAI1@Nucleus map

Participates in reactions:
As Reactant or Product:

  1. SNAI1@Nucleus map + HDAC1@Nucleus map + HDAC2@Nucleus map + SIN3A@Nucleus map map HDAC1:​HDAC2:​SIN3A:​SNAI1@Nucleus map

  2. EZH2@Nucleus map + SNAI1@Nucleus map + HDAC1@Nucleus map + HDAC2@Nucleus map map EZH2:​HDAC1:​HDAC2:​SNAI1@Nucleus map
  3. rHDAC2@Nucleus map map HDAC2@Nucleus map
  4. CBF1*@Nucleus map + CIR1@Nucleus map + SIN3A@Nucleus map + HDAC2@Nucleus map map CBF1*:​CIR1:​HDAC2:​SIN3A@Nucleus map

As Catalyser:

  1. gE-Cadherin*@Nucleus map map rE-Cadherin*@Nucleus map

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