Phosphorylation |
IGF-induced |
AKT |
S21 |
Decreases H3K27me3 level, releases EZH2 silenced target genes and promotes tumor development. |
[31] |
Non-genomic ER signaling |
AKT |
S21 |
Reduces the activity of H3K27me3 and HMTase. |
[77] |
Tat |
AKT |
S21 |
Decreases H3K27me3 level and increases EZH2 cytoplasmic translocation, activating HIV-1 transactivation. |
[80,81] |
As3+
|
AKT |
S21 |
Enhances Akt activation by upregulation of negative Akt regulator miR-21 via STAT3 S27 phosphorylation, contributing to pS21 EZH2 and oncogenesis. |
[82,83] |
GSCs |
AKT |
S21 |
Promotes EZH2-mediated STAT3 methylation, enhances EZH2-STAT3 interaction and STAT3 activity |
[84] |
- |
CDK1 and CDK2 |
T350 in human |
Enhances the silencing of target genes without affecting intrinsic HMTase activity or core PRC2 complex formation, promotes EZH2-mediated cell proliferation and migration. |
[86] |
- |
CDK1 |
T345 in Mouse |
Increases Ezh2 interaction with HOTAIR and the 5’end of Xist, further mediating PRC2 recruitment to its target loci and tumor progression. |
[87] |
- |
CDK1 |
T492 in human (T487 in Mouse) |
1. Inhibit HMTase activity, disrupt binding to other PRC2 components |
[87,91,92] |
2. Promote ubiquitination and degradation by proteasome pathway |
- |
CDK1 |
T487 in Human |
Suppresses EZH2 HMTase activity and disassociates EZH2 from other PRC2 complex components, finally inhibiting cancer cell migration and invasion and promoting human mesenchymal stem cells differentiation into osteoblasts. |
[91] |
MKK6 or TNFα |
p38α Kinase |
T372 in Mouse |
Enhances interaction of YY1 and PRC2, represses Pax7 expression and impair satellite cell proliferation |
[96] |
Acetylation |
- |
PCAF |
K348 |
Enhances EZH2 stability, promotes lung cancer cell migration and invasion |
[32] |
Ubiquitination |
- |
Smurf2 |
L421 |
Upregulates target gene PPARγ, essential for neuron differentiation of hMSCs and functional regeneration of CNS repair after ischaemic stroke |
[33] |
Jak2-induced pY461 EZH2 |
β-TrCP |
- |
Reduces EZH2 protein stability and H3K27me3 activity |
[110] |
YC-1, PKA and Src-Raf-1-MEK-ERK pathways |
c-Cbl |
T731 and T774 |
Leads to Src and ERK activation, resulting in formation of c-Cbl-ERK-EZH2 complex and enhancement of EZH2 uniquitination and degradation. |
[111] |
DZNep treatment |
PRAJA1 |
- |
Ub-mediated proteasomal degradation of individual PRC2 subunits including EZH2, SUZ12 and EED |
[112] |
FOXP3 |
PRAJA1 |
- |
Facilitates EZH2 protein degradation through K48-linkage polyubiquitination and decreases cell proliferation, migration and formation in breast cancer cells |
[113] |
- |
ω-3 PUFAs |
- |
Decreases EZH2 expression and H3K27me3 level, upregulates EZH2 downstream target genes E-cadherin and IGFBP3, leading to suppression of tumor invasion and metastasis. |
[114] |
Sumoylation |
- |
- |
- |
EZH2 are sumoylated in vitro and vivo, but the biological functions remain unknown. |
[34] |
O-GlcNAcylation |
OGT-dependent |
- |
S75 |
Maintains EZH2 protein stability H3K27me3 activity, eventually contributing to tumorigenesis |
[35] |