Table 1.
Non-canonical regulators of HH-GLI signaling in MB.
| Upstream regulator | Mechanism of action | Reference |
|---|---|---|
| Tumor suppressors | ||
| p53 | Promotes proteasome-dependent degradation of GLI1 (PCAF-dep.) | 62 |
| NUMB | Induces GLI1 ubiquitination and proteasome degradation (ITCH-dep.) | 63 |
| BCL6 | Directly represses Gli1 and Gli2 | 64 |
| PI3K-AKT-mTOR pathway | ||
| mTOR/S6K1 | HH signaling increases SMO translation through a mTORC1/4EBP1-dependent mechanism | 65 |
| MAPK pathway | ||
| MEKK1 | Inhibits GLI1 transcriptional activity | 66 |
| MEKK2/3 | Inhibits GLI1 transcriptional activity and protein stability through SUFU | 67 |
| p38 | The inhibition of p38α causes a decrease in Gli1 and N-myc transcript levels | 68 |
| DYRK family | ||
| DYRK1A | Increase the transcriptional activity of GLI1 | 69 |
| DYRK1B | Enhances GLI1 transcriptional activity | 70 |
| BET proteins | ||
| BRD4 | Increases GLI1/2 transcription | 71 |
| HDAC | ||
| HDAC class I | Increases DNA binding ability of GLI1 (HDAC1) | 72 |
| HDAC class II | Transcriptional control of GLI2 (HDAC6) | 73 |
| HAT | ||
| PCAF | Acts as GLI1 transcriptional cofactor Promotes GLI1 ubiquitination and proteolysis |
74 62 |
| Arbb1/p300 | Suppresses the transcriptional activity of Gli1 | 75 |