From: Post-translational modifications of PRC2: signals directing its activity
Type of PTM | Subunit | Condition | Modifying enzymes | Sites (human residue) | Function | References |
---|---|---|---|---|---|---|
Methylation | EZH2 | PRC2 | K510, K514 and K515 | Facilitates PRC2 access to histone H3K27 substrate, critical for H3K27me3 catalysis | [113, 125] | |
SUZ12 | PRC2 | Unknown | Unknown | [113] | ||
JARID2 | PRC2 | K116 | Allosteric activation of PRC2 | [100] | ||
Phosphorylation | EZH2 | IGF-induced | PKB/Akt | S21 | Disturbs PRC2 interaction with histone H3, inhibits PRC2 catalytic activity, decreases H3K27me3 level | [126] |
CDK1 | T345 (mouse) | Promotes PRC2 interaction with HOTAIR, recruitment, promotes ubiquitin-mediated degradation | [128, 134] | |||
TNFα | p38α | T372 (mouse) | Enhances PRC2 interaction with YY1, recruitment | [127] | ||
CDK2 | T416 | Enhances PRC2 interaction with NIPP1, recruitment | [129, 130] | |||
AMPK | T311 | Disrupts binding to other PRC2 components, inhibits PRC2 catalytic activity | [131] | |||
JAK3 | Y244 | Disrupts binding to other PRC2 components, inhibits PRC2 catalytic activity | [132] | |||
CDK1 | T487 (mouse) | Disrupts binding to other PRC2 components, decreases H3K27me3 level, promotes ubiquitin-mediated degradation | [133, 134] | |||
CDK5 | T261 | Promotes ubiquitin-mediated degradation | [136] | |||
JAK2 | Y641 | Promotes ubiquitin-mediated degradation | [135] | |||
SUZ12 | PLK1 | S539, S541 and S546 | Disrupts binding to other PRC2 components, promotes ubiquitin-mediated degradation | [137] | ||
ESC (Drosophila) | CK1/CK2 | N-terminus | EED homodimerization and larger PRC2 complex stability | [138] | ||
Acetylation | EZH2 | PCAF | K348 | Enhances EZH2 stability | [141] | |
Ubiquitination | EZH2 | Neuron differentiation | Smurf2 | K421 | Promotes EZH2 degradation and subsequent PRC2 disassociation | [144] |
CDK5-mediated phosphorylation at T261 | β-TRCP (FBXW1) | Unknown | Promotes EZH2 degradation, inhibits PRC2 catalytic activity | [136] | ||
JAK2-mediated phosphorylation at Y641 | FBXW7 | Unknown | Promotes EZH2 degradation, inhibits PRC2 catalytic activity | [135] | ||
SUZ12 | PLK1-mediated phosphorylation at S539, S541 and S546 | Unknown | Unknown | Promotes SUZ12 degradation and subsequent PRC2 disassociation | [137] | |
DZNep treatment | PRAJA1 | Unknown | Promotes EZH2, EED and SUZ12 degradation and subsequent PRC2 disassociation | [145] | ||
SUMOylation | EZH2 | Unknown | Unknown | Unknown | [150] | |
SUZ12 | PIASXβ | K75 | Unknown, dispensable for PRC2 localization and catalytical activity | [150] | ||
O-GlcNAcylation | EZH2 | OGT | S73, S76, S84, S87 and T313 | Enhances stability of isolated EZH2 | [154, 155] | |
OGT | S729 | Critical for H3K27me2/3 catalysis | [155] |