Table 3.
Post translational modification on ETS transcription factors and functional effects related to oncogenesis
| ETS protein | Modifying agents/Signaling events |
Type of post translational modification |
Effects | Pathology involving changes in post translational modification |
Reference |
|---|---|---|---|---|---|
| TEL | MAPK | Phosphorylation | Loss of repression and export to nucleus | Leukemia | (Wood et al., 2003) |
| SUMO conjugating enzyme UBC9 |
Sumoylation | ||||
| Ets-1 | CAMKII | Phopshorylation | Inhibits DNA binding and transcriptional activation |
(Nelson et al., 2010, Foulds et al., 2004) |
|
| MAPK | Phosphorylation | Allows for cooperative transcriptional activation of Ets-1 and AP1, recruitment of p300/CBP to Ets-1, and transcriptional activation of MMP and uPA genes |
|||
| TGFβ | Acetylation | Dissociation of p300/CBP, relieving ETS mediated activation, and making p300/CBP available for interaction with SMADs to activate transcription of ECM maintenance proteins |
Invasive breast carcinoma |
(Czuwara-Ladykowska et al., 2002) | |
| Ets-2 | MAPK | Phopshorylation | Increases activation and protein stability | Invasive breast cancer, Leukemia |
(Nelson et al., 2010, Foulds et al., 2004, Yang et al., 1996) |
| ELK-1 | MAPK | Phosphorylation | Increased DNA binding affinity and ELK- 1/SRF ternary complex formation, increase transcriptional activation |
Cervical cancer (HeLa) | (Lee, 2005, Latinkic et al., 1996, Tian and Karin, 1999) |
| SUMO conjugating enzyme UBC9 |
Sumoylation | Recruitment of HDACs, repression of transcriptional activation |
(Yang and Sharrocks, 2004, Yang et al., 2003) |
||
| ELF-1 | Agents unidentified |
Phosphorylation | Maximal activation of the ELF-1 promoter,converts ELF-1 from 80KDa to 98KDa,dissociates from Rb in cytoplasm and translocates to nucleus |
(Juang et al., 2002) | |
| Glycosylation | |||||
| Er81 | HER2/Neu signaling; MAPK |
Phosphorylation | Activates transcription | Breast cancer | (Bosc et al., 2001, Janknecht, 2001, Wang et al., 2011) |
| MSK1, PKA, Mk2 | Suppresses transcriptional activity | ||||
| p300;P/CAF | Acetylation | Increases DNA binding affinity and potency of Er81 TAD; inhibits ubiquitin mediated degradation. |
(Goel and Janknecht, 2003) | ||
| SAP-1 | MAPK | Phosphorylation | Increases DNA affinity, promotes ternary complex, increases transcriptional activation |
(Strahl et al., 1996) | |
| NET | Ras-ERK | Phosphorylation | Converts repressor to activator, stimulates angiogenesis |
(Giovane et al., 1994) | |
| JNK | Phosphorylation | ||||
| SUMO conjugating enzyme UBC9 |
Sumoylation | Increases repression | (Wasylyk et al., 2005) |